title: Neuromuscular Blockade in the Intentive Care Unit, an Observational Study.

acronym: CURATIV

summary:
The study Short description of the protocol intended for the lay public. Include a brief statement of the study hypothesis. (Limit: 5000 characters) Neuromuscular blocking agents (NMBAs) are drug capable of inducing a complete paralysis of the muscle. Their use is frequent in the intensive care unit (ICU). Most of the time it is used as a single infusion to facilitate endotracheal intubation, but in the ICU the use of continuous infusion is common in several pathologies: acute distress respiratory syndrome, post-cardiac arrest survivor under hypothermia to prevent shivering, abdominal compartment syndrome, severe traumatic brain injury with uncontrolled intra-cranial pressure and severe asthma among others.

A monitoring of the dose of NMBAs is recommended to guide the depth of paralysis and to guide recovery, but in the ICU, the interest of such a monitoring during continuous infusion is unclear and the level of evidence is low.

The investigators propose to conduct a prospective multicentric observational study to describe the current practice in the use of NMBAs in mechanically ventilated patients in the ICU. As a primary objective we will describe the prevalence of NMBAs use in the ICU. As a secondary objective, the investigators will investigate the impact of protocol and/or monitoring devices of NMBAs on the dose administered and clinical outcome endpoints.

ReferenceCitation: Arroliga A, Frutos-Vivar F, Hall J, Esteban A, Apezteguía C, Soto L, Anzueto A; International Mechanical Ventilation Study Group. Use of sedatives and neuromuscular blockers in a cohort of patients receiving mechanical ventilation. Chest. 2005 Aug;128(2):496-506.

ReferenceCitation: Arroliga AC, Thompson BT, Ancukiewicz M, Gonzales JP, Guntupalli KK, Park PK, Wiedemann HP, Anzueto A; Acute Respiratory Distress Syndrome Network. Use of sedatives, opioids, and neuromuscular blocking agents in patients with acute lung injury and acute respiratory distress syndrome. Crit Care Med. 2008 Apr;36(4):1083-8. doi: 10.1097/CCM.0B013E3181653895.

ReferenceCitation: Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, Gattinoni L, van Haren F, Larsson A, McAuley DF, Ranieri M, Rubenfeld G, Thompson BT, Wrigge H, Slutsky AS, Pesenti A; LUNG SAFE Investigators; ESICM Trials Group. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. JAMA. 2016 Feb 23;315(8):788-800. doi: 10.1001/jama.2016.0291. Erratum in: JAMA. 2016 Jul 19;316(3):350. JAMA. 2016 Jul 19;316(3):350.

ReferenceCitation: Papazian L, Forel JM, Gacouin A, Penot-Ragon C, Perrin G, Loundou A, Jaber S, Arnal JM, Perez D, Seghboyan JM, Constantin JM, Courant P, Lefrant JY, Guérin C, Prat G, Morange S, Roch A; ACURASYS Study Investigators. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med. 2010 Sep 16;363(12):1107-16. doi: 10.1056/NEJMoa1005372.

ReferenceCitation: Lascarrou JB, Le Gouge A, Dimet J, Lacherade JC, Martin-Lefèvre L, Fiancette M, Vinatier I, Lebert C, Bachoumas K, Yehia A, Lagarrigue MH, Colin G, Reignier J. Neuromuscular blockade during therapeutic hypothermia after cardiac arrest: observational study of neurological and infectious outcomes. Resuscitation. 2014 Sep;85(9):1257-62. doi: 10.1016/j.resuscitation.2014.05.017. Epub 2014 Jun 2.

ipd_sharing_description: IPD can be obtained from PI after careful evaluation of request by clinical research committee of the French Intensive Care Society

lead_sponsor: French Society for Intensive Care

location_facility:
CHU Nantes
CHRU Bretonneau
CHU Kremlin-Bicetre
CHR Orléans
CH de Pontoise
CH Le Mans
CH de Versailles
CHD Les Oudairies
CHU Nimes
CHU La Pitié Salpétrière
CH d'Argenteuil


title: Microbial Biomarkers of EArly Pseudomonas Aeruginosa Colonization in CHildren With Cystic Fibrosis

acronym: BEACH

summary: The objective of this study is to evaluate the predictive nature of the biomarker Porphyromonas catoniae measured at the age of 12 months in the occurrence of colonization with Pseudomonas aeruginosa at 24 months of age in children with cystic fibrosis.

study_start_date_type: Actual

status: Recruiting

study_completion_date_type: Anticipated

study_type: Interventional

primary_purpose: Diagnostic

enrollment_type: Anticipated

ipd_sharing: Yes

ipd_sharing_description: All collected data that underlie results in a publication

lead_sponsor: University Hospital, Brest

location_facility:
CHRU Rennes
Hôpital Charles Nicolle Rouen
Hôpital des Enfants Bordeaux
CHRU Angers
Hôpital Trousseau
CHU Grenoble
Hôpital Femme-Mère-Enfant Lyon
Centre de Perharidy
Hôpital Necker
CHRU de Tours
CHRU Nantes

intervention_type: Diagnostic Test

lead_sponsor_type: academique

status_simplified: Ongoing


title: Poetry Study - ProGrip™ Self-gripping Polyester Mesh Prospective Embedded REgisTRY for Abdominal Wall Sutureline Reinforcement in Subjects Undergoing Midline Laparotomy to Prevent Incisional Hernia

acronym: POETRY

summary:
Interventional, prospective, multicenter, post-marketing clinical follow-up study.

After midline laparotomy, the probability to develop an incisional hernia ranges from 10% to 50% depending on the complexity of the surgery and patient state of health.

As the clinical data needed for the study corresponds with those collected by Club Hernie registry, the clinical study will use the established registry database to collect performance and safety data on the prevention of incisional hernias within 24 months post operatively.

status: Active, not recruiting

primary_purpose: Treatment

enrollment_type: Actual

ipd_sharing: No

lead_sponsor: Medtronic - MITG

location_facility:
CHU Besançon
CHU de Rennes - Hôpital Pontchaillou
CHU Hopitaux de Rouen
CHU de Nantes
CHU de Bordeaux - Hôpital Haut-Lévêque
CHU Strasbourg - Nouvel Hôpital Civil
CHU Lille
CHU de Bordeaux
CHU de Nîmes
Centre Hospitalier Lyon Sud
HCL Louis Pradel

intervention_type: Device

lead_sponsor_type: industriel


acronym: IMMUNEBOOST

intervention_type: Radiation

title: A Multicenter, Randomized, Open Label, Phase II Study Evaluating the Feasibility and Tolerance of Nivolumab Neoadjuvant Immunotherapy in High Risk HPV Driven Oropharynx Cancer

lead_sponsor: UNICANCER

type: EudraCT Number

source: euctr

design_allocation: Randomized

ipd_sharing_description: Unicancer will share de-identified individual data that underlie the results reported. A decision concerning the sharing of other study documents, including protocol and statistical analysis plan will be examined upon request.

location_facility: Institut de cancerologie de Lorraine Alexis Vautrin

summary: The aim of this research is to study the feasibility of neoadjuvant treatment before chemoradiation in "high risk" HPV-driven Oropharynx cancer


title: A Randomized Phase III Trial Assessing a Regorafenib-irinotecan Combination (REGIRI) Versus Regorafenib Alone in Metastatic Colorectal Cancer Patients After Failure of Standard Therapies, According to the A/A Genotype of Cyclin D1

acronym: NEXT-REGIRI

summary: Patients with metastatic colorectal cancer (mCRC) who have received all approved standard treatments (except Regorafenib and TAS 102) no longer have treatment options available while maintaining a good performance status which would allow them to receive a new treatment

ReferenceType: background

ReferenceCitation: Samalin E, Bouché O, Thézenas S, Francois E, Adenis A, Bennouna J, Taieb J, Desseigne F, Seitz JF, Conroy T, Galais MP, Assenat E, Crapez E, Poujol S, Bibeau F, Boissière F, Laurent-Puig P, Ychou M, Mazard T. Sorafenib and irinotecan (NEXIRI) as second- or later-line treatment for patients with metastatic colorectal cancer and KRAS-mutated tumours: a multicentre Phase I/II trial. Br J Cancer. 2014 Mar 4;110(5):1148-54. doi: 10.1038/bjc.2013.813. Epub 2014 Jan 9.

ReferenceCitation: Lu F, Gladden AB, Diehl JA. An alternatively spliced cyclin D1 isoform, cyclin D1b, is a nuclear oncogene. Cancer Res. 2003 Nov 1;63(21):7056-61.

ReferenceCitation: Alt JR, Cleveland JL, Hannink M, Diehl JA. Phosphorylation-dependent regulation of cyclin D1 nuclear export and cyclin D1-dependent cellular transformation. Genes Dev. 2000 Dec 15;14(24):3102-14.

ReferenceCitation: Grothey A, Van Cutsem E, Sobrero A, Siena S, Falcone A, Ychou M, Humblet Y, Bouché O, Mineur L, Barone C, Adenis A, Tabernero J, Yoshino T, Lenz HJ, Goldberg RM, Sargent DJ, Cihon F, Cupit L, Wagner A, Laurent D; CORRECT Study Group. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013 Jan 26;381(9863):303-12. doi: 10.1016/S0140-6736(12)61900-X. Epub 2012 Nov 22.

lead_sponsor: Institut du Cancer de Montpellier - Val d'Aurelle

location_facility:
Hôpital Saint-Jean
Centre Antoine Lacassagne
Hôpital Européen Georges Pompidou
Centre Léon Bérard
Hôpital Robert Debré
Institut Gustave Roussy
CRLC Val d'Aurelle-Paul Lamarque
Hôpital Pontchaillou
Institut Godinot
Centre François Baclesse
Hôpital privé Jean Mermoz

intervention_type: Drug


acronym: GUIDE

title: A Phase 3b, Randomized, Double-blind, Parallel Group, Multicenter Study to Evaluate Further Therapeutic Strategies With Guselkumab in Patients With Moderate-to-Severe Plaque-Type Psoriasis

lead_sponsor: Janssen-Cilag G.m.b.H

type: Other Identifier

ReferenceType: derived

ReferenceCitation: Eyerich K, Weisenseel P, Pinter A, Schäkel K, Asadullah K, Wegner S, Muñoz-Elias EJ, Bartz H, Taut FJH, Reich K. IL-23 blockade with guselkumab potentially modifies psoriasis pathogenesis: rationale and study protocol of a phase 3b, randomised, double-blind, multicentre study in participants with moderate-to-severe plaque-type psoriasis (GUIDE). BMJ Open. 2021 Sep 13;11(9):e049822. doi: 10.1136/bmjopen-2021-049822.

ipd_sharing_description:
The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency.

As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

location_country: Germany France

location_facility: Zentderma BAG Dres. Ostendorf - Bohm - Jo GbR

location_facility: ISA - Interdisciplinary Study Association GmbH

location_facility: Company for Medical Study & Service Selters

location_facility: Universitatsklinikum Schleswig-Holstein - Kiel

location_facility: Harzklinikum Dorothea Christiane Erxleben GmbH - Germnay

location_facility: Polyclinique Reims Bezanne - De Courlancy

summary: The purpose of this study is to demonstrate that Super-Responders (SRe; defined as psoriasis participants who receive on-label guselkumab treatment until week 20 and respond with a Psoriasis Area and Severity Index score (PASI) = 0 at weeks 20 and 28) maintain control of disease until week 68 with prolonged treatment intervals of 16 weeks (guselkumab 100 mg every 16 weeks).


title: Aprepitant Versus Hydroxyzine in Association With Cytoreductive Treatments for Patients With Myeloproliferative Neoplasia Suffering From Persistent Aquagenic Pruritus.

acronym: APHYPAP

summary: Phase 3, randomized prospective study, double blind-double placebo, testing oral therapies APREPITANT versus HYDROXYZINE in patients followed for myeloproliferative neoplasms and suffering of persistent aquagenic pruritus.

ReferenceCitation: Le Gall-Ianotto C, Verdet R, Nowak E, Le Roux L, Gasse A, Fiedler A, Carlhant-Kowalski D, Marcorelles P, Misery L, Ianotto JC. Rationale and design of the multicentric, double-blind, double-placebo, randomized trial APrepitant versus HYdroxyzine in association with cytoreductive treatments for patients with myeloproliferative neoplasia suffering from Persistent Aquagenic Pruritus. Trial acronym: APHYPAP. Trials. 2021 Dec 19;22(1):938. doi: 10.1186/s13063-021-05864-8.

location_facility:
CHU Grenoble Alpes
CHU de Caen
Centre Hospitalier de Douarnenez
Centre Hospitalier des Pays de Morlaix
CHU de Nantes
CHU d'Angers
Centre Léon Bérard
CHRU de Brest - Hôpital Morvan
Hôpital Pontchaillou
Hôpital Yves Le Foll
Centre Hospitalier de Cornouaille


title: Multicentric, Open, Randomized Study Comparing Topical Treatment by Patch of Capsaicin to 8% (Qutenza) to Pregabalin Oral in the Early Treatment of Neuropathic Pain After Primary Surgery for Breast Cancer

acronym: CAPTRANE

summary:
Breast cancer is the most common cancer in women in Europe. Therefore, breast cancer has become a chronic disease and patients need to learn to live with it as well as with the adverse effects related to the disease itself or to the therapies used.

As noted in the third "Plan cancer", pain is a major criterion in the quality of life of patients treated for breast cancer.

Neuropathic pain was defined in 2011 by the international Association for the Study of Pain (I.A.S.P.) as the direct result of a lesion or disease affecting the somato-sensory system.

Surgical treatment is often the first treatment of breast cancer. It can be conservative by performing a partial mastectomy (lumpectomy or quadrantectomy) or non-preservative by total mastectomy.

Intercostobrachial neuralgia (NICB) or Post mastectomy painful Syndrome (MPRR) was first described by Wood in 1978 as "chronic pain beginning immediately or early after a mastectomy" Or a lumpectomy affecting the anterior thorax, armpit and/or arm in its upper half. These post-surgical pains are related to a lesion of the nerves in the breast area.

In particular, the intercostobrachial nerve can be severed, stretched or crushed during surgery.

Post-operative neuropathic pain in patients with breast cancer is underdiagnosed either by general practitioner or in a specialized environment.

The diagnosis of neuropathic pain is performed during examination and clinical examination. Several scales allow to detect neuropathic pain but only the DN4 is recognized to be the most specific and sensitive scale.

Patients do not always express this pain. They do not always reconcile with the surgery. Either because the pain occurs a long time after the surgery, or they find it normal to get hurt. These diagnostic difficulties cause a delay in setting up a suitable analgesic treatment.

However, neuropathic pain responds poorly to common analgesics. Diagnosis, evaluation and early management of neuropathic pain are a priority in order to avoid their chronicization, to improve the quality of life of patients with breast cancer and to enable them to return to work quickly.

We therefore assume that the diagnosis of early neuropathic pain at 2 months of surgery associated with initiation of appropriate topical treatment without the systemic effects of conventional oral treatments, would reduce the incidence of Chronic neuropathic pain 6 months after surgery.

primary_purpose: Supportive Care

lead_sponsor: Institut Cancerologie de l'Ouest

location_facility:
Institut de Cancerologie de L'Ouest
Chu Grenoble
Institut Jean Godinot
Ch Valenciennes
Iuct Oncopole
CHU NICE
Centre Oscar Lambret
Centre Leon Berard
Chd Vendee
Institut Curie
Hopital Saint Vincent de Paul


title: Long-term Outcome After Heparin and Edoxaban Versus Heparin Plus Vitamin K Antagonists for Acute Deep Vein Thrombosis and Pulmonary Embolism HOKUSAÏ POST VT

summary: Centers that participated in the HOKUSAI VTE trial will be invited to collect follow of previously enrolled patients at least 2 years after the index VTE.

status: Unknown status

primary_purpose: Other

lead_sponsor: University Hospital, Montpellier

location_facility:
Dijon University Hospital
Montpellier University Hospital
Amiens University Hospital
APHP Hôpital Européen Georges Pompidou
Strasbourg University Hospital
Brest University Hospital
Angers University Hospital
Nice University Hospital
Le Mans Hospital
Clermont-Ferrand University Hospital
Grenoble University Hospital

intervention_type: Other

status_simplified: Unknown


title: OPTIBOT: Study Describing the Coverage, Cares and the Fertility of Patients of Less Than 45 Years With a Borderline Ovarian Tumor (BOT)

acronym: OPTIBOT

summary:
Retrospective and prospective multi-center study

Indication: Fertility-sparing surgery for patients with borderline ovarian tumor and fertility

Objectives:

Description of the characteristics of the patients of less than 45 years having a fertility-sparing surgery for borderline ovarian tumors, the modalities of care and their fertility.
Validation of a nomogram as an information medium to the patients concerned on their chance of alive birth according to their personal characteristics

Origin and nature of the specific data:

Extraction from the database " Tumeurs Malignes Rares de l'Ovaire " (TMRO)
Collection of retrospective further informations in the participating centers
Data collection from the patients (questionnaires) The data will be identified by the TMRO number allocated to every participant of the TMRO study .

Data traffic :

TMRO database extraction for the patients with BOT and corresponding to the inclusion criteria, supplied by Arcagy-Gineco.

The database will be managed by the coordination team in an anonymous way by means of the patient identifiers of the TMRO base.

Enrichment of the base by the anonymous questionnaires filled by the patients and the complementary data transmissions of the centers on anonymised files.

status: Completed

study_completion_date_type: Actual

study_type: Observational

time_perspective: Other

lead_sponsor: Institut Curie

location_facility: Centre Hospitalier Intercommunal Poissy - Saint-Germain

location_facility: Institut de Cancérologie de Lorraine - Centre Alexis VAUTRIN

location_facility: Goupe Hospitalier Diaconesses Croix Saint-Simon

location_facility: IUCT Oncopole - Institut Claudius Regaud

status_simplified: Completed


title: Early Versus Differed Arterial Catheterization in Critically Ill Patients With Acute Circulatory Failure: A Multicentre, Open-label, Pragmatic, Randomised, Non-inferiority Controlled Trial (EVERDAC Trial)

acronym: EVERDAC

summary:
The objective of the present research is a combination of a one-sided test of non-inferiority and a one-sided test of superiority. A stepped approach will be used to evaluate these hypotheses:

a less invasive intervention (i.e., no indwelling arterial catheter insertion until felt absolutely needed, according to consensual and predefined safety criteria) is non inferior to usual care (i.e., systematic indwelling arterial catheter insertion in the early hours of shock) in terms of mortality at day 28 (non-inferiority margin of 5%).
a less invasive intervention is not only non-inferior but also superior to usual care in terms of mortality.

Multi-centre, pragmatic, randomised, controlled, open, two-parallel group, non-inferiority clinical trial.

ReferenceCitation: Muller G, Kamel T, Contou D, Ehrmann S, Martin M, Quenot JP, Lacherade JC, Boissier F, Monnier A, Vimeux S, Brunet Houdard S, Tavernier E, Boulain T. Early versus differed arterial catheterisation in critically ill patients with acute circulatory failure: a multicentre, open-label, pragmatic, randomised, non-inferiority controlled trial: the EVERDAC protocol. BMJ Open. 2021 Sep 14;11(9):e044719. doi: 10.1136/bmjopen-2020-044719.

lead_sponsor: University Hospital, Tours

intervention_type: Procedure


title: Long-term Review of a Cohort of Arthroscopic Bankart Interventions

summary:
Recurrent instability is the most common chronic shoulder pathology of the young and athletic patient. It is a source of functional, sporting and professional disability, and a permanent apprehension to the use of the affected shoulder.

Surgical treatment has been proposed for a long time by the reintegration of the labrum (intervention of Bankart) then by the making of an osteo-muscular stop (intervention of Latarjet).

Like in many domains, surgical techniques have evaluated towards the search for endoscopic alternatives to open surgery, more deleterious.

Bankart's intervention has been performed arthroscopically since the 1980s and remains the majority intervention in the United States. However, its success rate never reached that of open techniques, Bankart and Latarjet. Surgeons therefore sought the predictors of these failures in order to define the limits of the indications for arthroscopic Bankart intervention.

The determination and use of the preoperative instability score (Instability Severity Index Score : ISIS) described by Balg and Boileau is one of the ways to clarify these indications.

The aim of this study is to prospectively establish the values of the ISIS score to obtain an acceptable recurrence rate of long-term instability

time_perspective: Prospective

ipd_sharing: Undecided

lead_sponsor: Rennes University Hospital

location_facility: Centre Hospitalier Universitaire de RENNES


title: Evaluation of the Long-term Efficacy of the Injection of Botulinum Toxin A Into the Salivary Glands Versus Scopolamine Patches in the Treatment of Drooling in Children Over 4 Years Old With Cerebral Palsy.

acronym: TOXSIALO

summary:
Cerebral palsy is the first cause of motor disability in developed countries. It is associated with altered motor function but also with mental, sensorial and behavior deficiencies. Drooling frequently occurs in children with cerebral palsy (37 to 58%). It causes multiple medical and social complications which can all increase disability and reduce quality of life for the patients and their family. Drooling treatments are various and includes orofacial rehabilitations, anticholinergic medications, botulinum toxin A and B salivary gland injections. Surgeries could also be used, but their benefits are often outweighed by the risk.

Orofacial rehabilitation is firstly recommended, even if few studies evaluated its efficacy.
Medication by Scopoderm®, a cutaneous anticholinergic drug, is frequently used in spite of frequent side effects and a lack of evidence regarding efficacy.
Botulinum toxin salivary gland injections (Botox®) were shown to be effective in reducing the severity of drooling consequences for the patient quality of life up to 12 months after the injections (Reid 2008).

A recent survey carried showed that treatment by Botox® injection would be preferred by professional to Scopoderm® patch, because of better tolerance and efficacy, even if Scopoderm® remained more used by professionals (Chaleat-Valayer 2016). However, a Cochrane review (Walshe 2012) concluded that there is 1) no strong consensus regarding assessment or the timing of all treatments 2) not enough efficacy studies with high level of evidence, 3) mostly efficacy studies vs placebo or no intervention 4) a lack of long term treatment assessment 5) a lack of studies on the patient quality of life.

Our study will be a comparative randomized clinical trial with an active control arm. The hypothesis is that therapeutic treatment of drooling in children with cerebral palsy consisting of a standardized rehabilitation treatment associated with a botulinum toxin A injection (Botox®) in the salivary glands is more effective than the same rehabilitation treatment associated with a treatment by scopolamine patches (Scopoderm®).

The main outcome will be assessed 15 months after initiation of treatment to evaluate long-term effectiveness. Patients from both arms of the trial will received rehabilitation, in order to compare treatment efficacy as it is done in real conditions of treatment. The efficacy of the treatment will be assessed on the impact of the drooling perceived by the patients and their family rather than on the measure of salivary production, as recommended (Walshe 2012).

lead_sponsor: Hospices Civils de Lyon

location_facility: Centre Médico-Chirurgical de Réadaptation des Massues


title: Randomized Phase II, 2-arm Study of Immunomodulation With Atezolizumab Concomitant With High Dose Radiation (SBRT) Versus SBRT Alone in Patients With Oligometastatic Sarcomas

acronym: Stereosarc

summary:
Up to 50% of soft tissue sarcoma (STS) patients will develop metastases in the course of their disease. Cytotoxic therapy is a standard treatment in this setting but yields average tumor response rates of 25% at first line and ≤10% at later lines. It is also limited in the number of lines and courses by tolerance issues. Trials include poly/oligometastases indistinctively and suggest that consolidation ablation is used in ~20% of patients with residual oligometastases refractory to chemotherapy. Oligometastases represent a stage of disease between completely absent and widely metastatic, and which might be cured if the limited numbers of metastatic sites are eradicated. Ablative strategies to treat patients with oligometastases from sarcomas yield prolonged survival times and stereotactic body radiation therapy (SBRT) is associated with excellent tolerance. Surgery may be offered in selected metastatic cases. Alternatively and increasingly, SBRT yields high control rates at treated sites (≥ 80%). The so-called radioresistance of sarcomas is overcome by the high doses per fraction made possible owing to the high precision achieved with SBRT. SBRT is an accepted treatment strategy provided that tumor burden remains limited in the number and size of metastases. Systemic treatment can be combined with SBRT. SBRT may produce abscopal effects where tumors outside the irradiation area also demonstrate tumor shrinkage in some occurrences. SBRT produces systemic antitumoral immune response in certain conditions and enhances radiation-induced tumor cell death compared to conventional lower dose irradiation. Abscopal effects have been potentialized with SBRT/immunotherapy in several tumor models. Sarcomas are a privileged target tumor given their high metastatic propensity.

Several potent immunomodulators that skew the tumor immune microenvironment toward a proimmunity context are being investigated in STS either alone or in combination with chemotherapy or targeted therapy. The PD-1 receptor is present within the tumor microenvironment, and limits the activity of infiltrating cytotoxic T lymphocytes, thus blocking effective immune responses. The action of PD-1 is triggered upon binding to its ligands. PD-1 can stimulate the immunosuppressive function of regulatory T cells. Moreover, blockade of PD-1 can stimulate anti-tumor immune responses. Significant responses have been obtained in several sarcomas with acceptable tolerance. Preliminary clinical experience suggests that immunotherapy can be efficient in refractory leiomyosarcomas. Several drugs targeting the PD-1/PD-L1/2 axis are ongoing either as single agents or in combination with ipilimumab, kinase inhibitors, or chemotherapy in STS subtypes. Combination of radiotherapy with immunotherapy is included as a means of increasing tumor antigen release in metastatic STS. Immunomodulated SBRT is a particularly attractive strategy, given the potential of radiation to induce cytotoxicity in tumors and induce abscopal effects. A phase II radiation trial showed increased apoptosis-, intra-tumoral dendritic cells and accumulation of intratumoral T cells in STS with correlation with tumor-specific immune responses.

We here propose a randomized phase II study to prolong progression-free survival (PFS) with the combination of SBRT/immunotherapy in oligometastatic STS patients.

SBRT is well-tolerated with hardly any severe toxicity (fewer than 5% acute and late grade 3 toxicities). It is performed in an ambulatory setting in only a few treatment fractions. Associations between irradiation and immunomodulatory agents appear to be synergistic and show favorable tolerance profiles. Immunomodulatory agents have a more favorable toxicity profile than cytotoxic agents with about 65% overall acute toxicities. Immunotherapy selectively binds to PD-L1 and competitively blocks its interaction with PD-1.

Compared with anti-PD-1 antibodies that target T-cells, immunotherapy targets tumor cells, and is therefore may induce fewer side effects, including a lower risk of autoimmune-related safety issues, as blockade of PD-L1 leaves the PD-L2 - PD-1 pathway intact to promote peripheral self-tolerance.

Stereotactic irradiation is associated with an excellent tolerance with rates of grade 3 or more toxicities below 5%.

Preliminary data of toxicity with the association of stereotactic irradiation and immunotherapy show no cumulative toxicity in association with immunotherapy. However, their incidence and characteristics are no different from that observed with stereotactic irradiation alone. Moreover, intracranial metastases are exceptional in sarcomas.

The toxicity of the association for extracranial stereotactic irradiation does not seem to be increased either.

ReferenceCitation: le Guevelou J, Debaigt C, Saada-Bouzid E, Viotti J, Khalladi N, Thibouw D, Penel N, Sunyach MP, Moureau-Zabotto L, Benchalal M, Veresezan O, Ducassou A, le Pechoux C, Jolnerovski M, Bazille C, Vaur D, Escande A, Serre R, Lovera C, Thariat J. Phase II study of concomitant radiotherapy with atezolizumab in oligometastatic soft tissue sarcomas: STEREOSARC trial protocol. BMJ Open. 2020 Sep 23;10(9):e038391. doi: 10.1136/bmjopen-2020-038391.

lead_sponsor: Centre Antoine Lacassagne

location_facility:
Institut Paoli CALMETTES
Centre Eugene MARQUIS
Centre François BACLESSE
Centre Antoine LACASSAGNE
Centre Henri BECQUEREL
Centre Léon BERARD
Institut de Cancérologie de Lorraine
Centre Oscar LAMBRET
Institut Claudius REGAUD
Centre Georges François LECLERC
Institut Gustave ROUSSY


title: Phase II Study, Stratified, Non-randomized, Estimating SBRT Efficiency and Toxicity in Primary and Secondary Liver Tumors

acronym: STEREOLIVER

summary: Intervention research involving the human person, phase II, prospective, multicentric, non-randomized and multi-cohort study. The eligibility criteria are broad, on purpose, so every patient, able to be treated by SBRT and unable to participate in another trial (non eligible patient or non included centers), can be included in this national study, in a prospective way.

lead_sponsor: Centre Oscar Lambret

location_facility: Institut Régional du Cancer de Montpellier

location_facility: Institut de Cancérologie Lucien Neuwirth


title: Interest of Denosumab Treatment in Osteoporosis Associated to Systemic Mastocytosis

acronym: DenosuMast

summary:
The study is looking at the efficacy of subcutaneously administrated denosumab 60 mg every 6 months versus placebo after 3 years, by analyze of lumbar spine bone mineral density (BMD) in systemic mastocytosis.

Investigators hypothesize that use of denosumab subcutaneously in patients with osteoporosis related to systemic mastocytosis is effective and safe to improve bone mineral density and prevent new bone events, based on targeted specific RANKL secretion by mast cells and short half-life of denosumab.

ReferenceCitation: Johnson MR, Verstovsek S, Jorgensen JL, Manshouri T, Luthra R, Jones DM, Bueso-Ramos CE, Medeiros LJ, Huh YO. Utility of the World Heath Organization classification criteria for the diagnosis of systemic mastocytosis in bone marrow. Mod Pathol. 2009 Jan;22(1):50-7. doi: 10.1038/modpathol.2008.141. Epub 2008 Sep 19.

ReferenceCitation: Theoharides TC, Valent P, Akin C. Mast Cells, Mastocytosis, and Related Disorders. N Engl J Med. 2015 Jul 9;373(2):163-72. doi: 10.1056/NEJMra1409760. Review.

ReferenceCitation: Frenzel L, Hermine O. Mast cells and inflammation. Joint Bone Spine. 2013 Mar;80(2):141-5. doi: 10.1016/j.jbspin.2012.08.013. Epub 2012 Oct 30. Review.

ReferenceCitation: Rabenhorst A, Christopeit B, Leja S, Gerbaulet A, Kleiner S, Förster A, Raap U, Wickenhauser C, Hartmann K. Serum levels of bone cytokines are increased in indolent systemic mastocytosis associated with osteopenia or osteoporosis. J Allergy Clin Immunol. 2013 Nov;132(5):1234-1237.e7. doi: 10.1016/j.jaci.2013.06.019. Epub 2013 Jul 31.

ReferenceCitation: Barete S, Assous N, de Gennes C, Grandpeix C, Feger F, Palmerini F, Dubreuil P, Arock M, Roux C, Launay JM, Fraitag S, Canioni D, Billemont B, Suarez F, Lanternier F, Lortholary O, Hermine O, Francès C. Systemic mastocytosis and bone involvement in a cohort of 75 patients. Ann Rheum Dis. 2010 Oct;69(10):1838-41. doi: 10.1136/ard.2009.124511. Epub 2010 Jun 22.

ReferenceCitation: van der Veer E, Arends S, van der Hoek S, Versluijs JB, de Monchy JGR, Oude Elberink JNG, van Doormaal JJ. Predictors of new fragility fractures after diagnosis of indolent systemic mastocytosis. J Allergy Clin Immunol. 2014 Dec;134(6):1413-1421. doi: 10.1016/j.jaci.2014.05.003. Epub 2014 Jun 27.

ReferenceCitation: Rossini M, Zanotti R, Viapiana O, Tripi G, Idolazzi L, Biondan M, Orsolini G, Bonadonna P, Adami S, Gatti D. Zoledronic acid in osteoporosis secondary to mastocytosis. Am J Med. 2014 Nov;127(11):1127.e1-1127.e4. doi: 10.1016/j.amjmed.2014.06.015. Epub 2014 Jun 20.

ReferenceCitation: Edwards BJ, Bunta AD, Lane J, Odvina C, Rao DS, Raisch DW, McKoy JM, Omar I, Belknap SM, Garg V, Hahr AJ, Samaras AT, Fisher MJ, West DP, Langman CB, Stern PH. Bisphosphonates and nonhealing femoral fractures: analysis of the FDA Adverse Event Reporting System (FAERS) and international safety efforts: a systematic review from the Research on Adverse Drug Events And Reports (RADAR) project. J Bone Joint Surg Am. 2013 Feb 20;95(4):297-307. doi: 10.2106/JBJS.K.01181. Review.

ReferenceCitation: Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, Delmas P, Zoog HB, Austin M, Wang A, Kutilek S, Adami S, Zanchetta J, Libanati C, Siddhanti S, Christiansen C; FREEDOM Trial. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009 Aug 20;361(8):756-65. doi: 10.1056/NEJMoa0809493. Epub 2009 Aug 11. Erratum in: N Engl J Med. 2009 Nov 5;361(19):1914.

lead_sponsor: Assistance Publique - Hôpitaux de Paris

location_facility: La Timone Hospital, Dermatology and cutaneous oncology department

location_facility: Lapeyronie Hospital, Rheumatology and Immunology department

location_facility: Caen Hospital, Clinical haematology department

location_facility: Lille CHRU Hospital, Internal medicine and clinical immunology department

location_facility: Toulouse Hospital, Dermatology department

location_facility: Necker Hospital, Adult haematology department

location_facility: Strasbourg Hospital, Rheumatology department

location_facility: Estaing Hospital, Cellular therapy and clinical haematology department

location_facility: Jean Minjoz Hospital, Dermatology department

location_facility: La Pitié-Salpêtrière Hospital, Internal medicine and clinical immunology department

location_facility: Cochin Hospital, Rheumatology department


title: Effect of Opioid-free Anesthesia on Postoperative Opioid-related Adverse Events After Major or Intermediate Non-cardiac Surgery: a Multicenter Prospective Randomized Controlled Study

acronym: POFA

summary:
Since the 1960's, intraoperative administration of opioids is considered a keystone of anesthesia as well as hypnotics and muscle relaxants. Synthetic opioids were introduced to achieve hemodynamic stability during anesthesia. They allow an inhibition of the sympathetic system without cardiovascular collapse and histamine release. Since then, anesthesia has changed from inhalation to multimodal anesthesia with lower doses of hypnotic. In 2017, the intraoperative objectives of hypnosis, hemodynamic stability, immobility and anticipation of postoperative analgesia can be achieved without opioids. Moreover, opioid administration consequences are neither scarce nor benign for the patient. Perioperative opioids are associated with nausea and vomiting, sedation, ileus, confusion/delirium, respiratory depression, increased postoperative pain and morphine consumption, immunodepression, hyperalgesia and chronic postoperative pain. Among these complications, hypoxemia, ileus and confusion/delirium are the most frequent.

Efficacious multimodal analgesia and anesthesia are the basis of successful fast-track surgery. These multidrug regimens aim at decreasing postoperative pain, intra- and postoperative opioid requirements, and subsequently, opioid-related adverse effects and to fasten recovery. Opioid-free postoperative analgesia has been recommended for more than 10 years. Opioid-free anesthesia (OFA) is based on the idea that hemodynamic stability can be achieved without opioids during anesthesia. OFA is multimodal anesthesia associating hypnotics, N-methyl-D-aspartate (NMDA) antagonists, local anesthetics, anti-inflammatory drugs and alpha-2 agonists (Dexmedetomidine).

Proofs of the effect of OFA on reducing opioid-related adverse effects after major or intermediate non-cardiac surgery are still scarce. We hypothesized that the reduced opioid consumption during and after surgery allowed by OFA compared with standard of care will be associated with a reduction of postoperative opioid-related adverse events.

status: Terminated

ReferenceCitation: Beloeil H, Laviolle B, Menard C, Paugam-Burtz C, Garot M, Asehnoune K, Minville V, Cuvillon P, Oger S, Nadaud J, Lecoeur S, Chanques G, Futier E; SFAR research network. POFA trial study protocol: a multicentre, double-blind, randomised, controlled clinical trial comparing opioid-free versus opioid anaesthesia on postoperative opioid-related adverse events after major or intermediate non-cardiac surgery. BMJ Open. 2018 Jun 30;8(6):e020873. doi: 10.1136/bmjopen-2017-020873.

location_facility:
Lille University Hospital
Montpellier University Hospital
Nimes University Hospital
Saint-Brieuc Hospital
Toulouse University Hospital
Perigueux Hospital
Metz-Thionville Hospital
Rennes University Hospital
Beaujon Hospital
Clermont-Ferrand University Hospital
Nantes University Hospital


title: Combined Use of Contact Aspiration and the Stent Retriever Technique Versus Stent Retriever Alone for Recanalisation in Acute Cerebral Infarction: the Randomized ASTER2 Study

summary:
Mechanical thrombectomy (MT) with a stent retriever (SR) device is now the standard intervention in ischemic stroke with large vessel occlusion. Favorable outcome is strongly associated with the successful reperfusion status. New device of MT such as contact aspiration seems promising to increase reperfusion status and clinical outcome.

The main hypothesis is to show the superiority of combining the use of contact aspiration with a stent retriever compared to a stent retriever alone in treatment of acute stroke due to proximal arterial occlusion.

The primary endpoint is the rate of perfect reperfusion score at the end of the endovascular procedure.

ReferenceCitation: Lapergue B, Blanc R, Costalat V, Desal H, Saleme S, Spelle L, Marnat G, Shotar E, Eugene F, Mazighi M, Houdart E, Consoli A, Rodesch G, Bourcier R, Bracard S, Duhamel A, Ben Maacha M, Lopez D, Renaud N, Labreuche J, Gory B, Piotin M; ASTER2 Trial Investigators. Effect of Thrombectomy With Combined Contact Aspiration and Stent Retriever vs Stent Retriever Alone on Revascularization in Patients With Acute Ischemic Stroke and Large Vessel Occlusion: The ASTER2 Randomized Clinical Trial. JAMA. 2021 Sep 28;326(12):1158-1169. doi: 10.1001/jama.2021.13827.

lead_sponsor: Hopital Foch

location_facility:
CHU Nantes
Hôpital Foch
CHU Montpellier
CHU Rennes
CHU Bordeaux
CHU Nancy
CHU Limoges
Kremlin-Bicêtre (APHP)
La Pitié-Salpétrière (APHP)
Lariboisière (APHP)
Fondation Ophtalmologique Rotschild

intervention_type: Combination Product


title: A Retrospective Analysis of the Outcome of Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML) Included in a Patient Named Program of Gemtuzumab Ozogamicin/Mylotarg®

acronym: MYLOR

summary:
Gemtuzumab Ozogamicin/Mylotarg® (GO) is a conjugate of a derivative of calicheamicin a potent antitumor anthracycline antibiotic linked to a recombinant humanized antibody against the CD33 antigen. Pivotal phase 2 study in relapsed AML adult patients used GO 9 mg/m2 as a monotherapy on days 1 and 14, and showed a 30% response rate with half CR and CRp (CR with incomplete platelets recovery). Four randomized studies, 3 in adults and 1 in children, performed in patients with non-previously treated AML tested the addition of lower doses of GO ( 3mg or 6 mg/m2) to standard induction chemotherapy and showed benefit on survival endpoints. Results from these studies were available in 2011 in adults and 2014 in children. In 2010 the french health agency (ANSM) opened a compassionate patient named program (authorization for temporary utilization (ATU) program) of GO in relapsed/refractory AML patients. Patients were orally informed about the status of the GO. From 2010 to 2012 it was recommended to use GO as a monotherapy at a dose of 9mg/m2 on days 1 and 14 according to the protocol used in pivotal phase 2 study. After 2012 it was recommended by the health authority to use GO at the dose of 3 or 6 mg/m2 in addition to chemotherapy regarding the toxicity of higher dose given once.

From 2010 to 2015 more than 500 AML patients have been included in this ATU program.

The main objective of the study presented here is to assess the efficacy and safety of GO 3 or 6 mg/m2 (single dose or fractionated GO) given in as treatment of relapsed/refractory AML in adult patients.

The coordinator choose to collect the data from centers that included 10 patients or more from January 2012 to December 2015.

This represents approximately 420 patients from 33 hematology departments.

time_perspective: Retrospective

lead_sponsor: Versailles Hospital

location_facility:
Hôpital de la Source
HIA Percy
C.H.U. d'Angers
Hôpital André Mignot
Hôpital Hotel Dieu
C.H.U. d'Amiens - Hôpital Sud
Hopital Saint Louis
Hôpital du Bocage
Hôpital Henri Mondor
C.H. Lyon Sud
Hôpital Brabois Adultes


title: LEAn Body Mass Normalization of OXaliplatin Based Chemotherapy for Stage III Colon Cancer Patients Treated in Adjuvant Setting: Impact on Oxaliplatin-induced Sensitive Neurotoxicity. A Multicenter Phase II Randomized Trial (LEANOX)

acronym: LEANOX

summary: Cytotoxic chemotherapy is usually scaled to the body surface area (BSA), and is currently not adjusted to the body proportions of lean and fat (i.e. body composition) of individual patients. Patients with low muscle mass behave like patients "overdosed" with chemotherapy resulted in dose-limiting toxicities (e.g. dose reductions, treatment delays or permanent treatment discontinuation), independently of the patient's weight.

location_facility: Institut regional du Cancer - Val d Aurelle

location_facility: Centre hospitalier régional et universitaire de Montpellier


title: A Multicentre Feasibility Randomized Study of Anti-PD-L1 Durvalumab (MEDI4736) With or Without Anti-CTLA-4 Tremelimumab in Patients With Ovarian, Fallopian Tube or Primary Peritoneal Adenocarcinoma, Treated With a First-line Neo-adjuvant Strategy

acronym: INeOV

summary: This is a randomized, open, comparative, multi-centre study which will recruit up to 66 patients. The objective is mainly to explore the safety and feasibility in neo-adjuvant first-line ovarian cancer (including patients with primary peritoneal or fallopian tube adenocarcinoma) of various combinations of durvalumab with chemotherapy with or without tremelimumab.

lead_sponsor: ARCAGY/ GINECO GROUP

location_facility:
Institut Bergonié
Hôpital Henri Duffaut
ICM Val d'Aurelle
Institut de Cancérologie de Lorraine
Centre Eugene Marquis
Hôpital Cochin
Groupe confluent
Institut René Godinot
Centre Hospitalier Lyon Sud
HEGP
Gustave Roussy


title: Impact of a Systematic Palliative Care on Quality of Life, in Advanced Idiopathic Pulmonary Fibrosis (IPF). A Randomized Multi-center Trial.

acronym: PALIF

summary:
Idiopathic pulmonary fibrosis (IPF) is a rare and severe disease with a survival median between 2 and 4 years which leads to a profound alteration of the quality of life.

In thoracic oncology, the systematic and early intervention of a palliative care team result in an improvement of quality of life for patients.

In the princeps study published in 2010, the early intervention of a dedicated palliative care team was compared to standard care in a randomized trial of 150 patients and shows a significant improvement : (i) of quality of life (main objective), (ii) of depression scores and even overall survival (11.6 months vs. 8.9 months, P = 0.02), (iii) a benefit in terms of understanding the diagnosis and therapeutic goals (3), (iv) diminution of adapted hospitalization in end of life (in emergency or not).

Considering some analogy points between IPF and advanced lung cancer (prognosis, respiratory symptom, psychological burden), it seemed reasonable to assume that the joint systematic intervention of chest physician and palliative care team may provide a significant benefit in terms of quality of life for patients with severe IPF.

ReferenceCitation: Swigris JJ, Brown KK, Behr J, du Bois RM, King TE, Raghu G, Wamboldt FS. The SF-36 and SGRQ: validity and first look at minimum important differences in IPF. Respir Med. 2010 Feb;104(2):296-304. doi: 10.1016/j.rmed.2009.09.006. Epub 2009 Oct 7.

ReferenceCitation: Swigris JJ, Kuschner WG, Jacobs SS, Wilson SR, Gould MK. Health-related quality of life in patients with idiopathic pulmonary fibrosis: a systematic review. Thorax. 2005 Jul;60(7):588-94. Review.

ReferenceCitation: Temel JS, Greer JA, Muzikansky A, Gallagher ER, Admane S, Jackson VA, Dahlin CM, Blinderman CD, Jacobsen J, Pirl WF, Billings JA, Lynch TJ. Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med. 2010 Aug 19;363(8):733-42. doi: 10.1056/NEJMoa1000678.

location_facility: Centre Hospitalier de Versailles Andre Mignot


acronym: NISCAHN

title: A Phase II, Multicenter, Non Randomized, Open Label Study of Nivolumab In Recurrent and/or Metastatic Salivary Gland Carcinoma of the Head and Neck

ipd_sharing_description: no individual participant data is shared

location_facility:
Centre René Gauducheau
Centre Georges François Leclerc
ICM Val d'Aurelle
Centre Paul Strauss
Centre Antoine Lacassagne
CHU Bordeaux
Centre Léon Bérard
Institut de cancérologie Alexis Vautrin
Institut Curie Saint Cloud
Institut Curie
Gustave Roussy

summary:
INDICATION:

Patients with recurrent and/or metastatic salivary glands carcinoma who have progressed during the 6 months period before entering the study and who are eligible for nivolumab monotherapy.


title: Active Surveillance With or Without a 6 Months Apalutamide Treatment in Low Risk Prostate Cancer: A Phase II Randomized Multicenter Trial

acronym: PC-ARN

summary:
Many prostate cancer are slow or non progressive forms that would never impair quality or quantity of like of life if undetected. For this localized prostate cancer, the recommendation is an active surveillance, however often experienced by the patient as a lack of care. Thus the introduction of new potent androgen receptor inhibitor raise the question of the benefit of early hormonal therapy in localized prostate cancers.

The aim of this study is to assess whether treatment with an oral androgen receptor inhibitor could influence the progression of localized prostate cancer and delay the time to local treatment initiation.

lead_sponsor: Institut Paoli-Calmettes

location_facility:
CHRU Hopital Edouard Herriot
Clinique Beau Soleil
Institut Paoli Calmettes
Clinique La Croix Du Sud
Chu de Nice
Chu Tenon
Chu Saint Etienne
Hia Sainte Anne
Chu Hotel Dieu
Chu Pontchaillou
Institut Mutualiste Montsouris


title: Comparison of 3 Diagnostic Strategies of Pulmonary Embolism : Planar Ventilation-perfusion Scintigraphy (Planar V/Q Scan), Computed Tomography Pulmonary Angiography (CTPA), and V/Q Single Photon Emission Computed Tomography (SPECT)

acronym: SPECTACULAR

summary:
Pulmonary embolism (PE) remains a diagnostic challenge. False negative testing exposes patient to the risk of potentially fatal recurrence. False positive testing exposes patients to potentially fatal unduly side effects of anticoagulants.

Current diagnostic strategies rely on the sequential use of pretest clinical probability, Ddimer test, and chest imaging. Two chest imaging modalities have been validated for PE diagnostic exclusion: Computed Tomography Pulmonary Angiography (CTPA) and planar V/Q scan. Main limitations of planar V/Q are the high proportion of non-conclusive results, therefore requiring additional testing and more complex diagnostic algorithms. Main limitations of CTPA are its higher radiation dose and contraindications (renal failure).

In a randomized trial that compared strategies based on CTPA and on planar V/Q scan, a 30% increase in the rate of PE diagnoses was found in the arm using CTPA, raising the hypothesis of over-diagnosing and over-treating PE when using CTPA.

V/Q Single Photon Emission CT (SPECT) is a new method of scintigraphic acquisition that has been reported to improve the diagnostic performances of the test, which could reduce the number of non-conclusive tests and allow simplified diagnostic algorithms.

The investigators hypothesize that a strategy based on V/Q SPECT could be an alternative to the two usual approaches responding rightly to the two mains issues and combining the advantages of CTPA (simplified diagnostic approach) and planar V/Q (no overdiagnosis, lower radiation exposure, no contraindication).

Although a recent survey showed that up to 70% of nuclear medicine centers perform SPECT rather than planar imaging for diagnosing PE, a diagnostic management outcome study, in which diagnostic decision would be made on the basis of a standardized algorithm based on the V/Q SPECT is lacking. Such a study needs to be conducted to ensure that the safety of diagnostic exclusion using a V/Q SPECT based strategy is non-inferior to that of previously validated strategies, and to verify that the use of V/Q SPECT does not lead to over-diagnosis.

lead_sponsor: University Hospital, Brest

location_country: France Switzerland

location_facility:
CHU la Réunion
Hopital Saint Esprit
CHU d'ANGERS
CHU Clermont Ferrand
CH Toulon
Geneva University Hospital
Hôpital des Armées Clermont Tonnerre
CHRU de Brest
CHU de Saint Etienne
CHU de Dijon
Hegp - Ap-Hp
CH des Pays de Morlaix


title: Diagnostic Reasoning and Sense of Alarm at Dyspnoea and / or Chest Pain

acronym: RaisDiag

summary: Dyspnea and chest pain represent 1.5% of general practice consultations. They may be a sign of many diseases, potentially serious. The concept of Gut Feelings brings a sense of alarm and reinsurance. The sense of alarm reflects a sense of mistrust about the patient's clinical situation, in the absence of objective argument. The sense of reinsurance reflects a sense of confidence about the patient's situation, in the absence of objective argument. Gut Feelings plays a key role in the diagnostic reasoning in general practice. A questionnaire measuring the Gut Feelings was validated in French after a linguistic validation procedure.

ReferenceCitation: Barais M, Fossard E, Dany A, Montier T, Stolper E, Van Royen P. Accuracy of the general practitioner's sense of alarm when confronted with dyspnoea and/or chest pain: a prospective observational study. BMJ Open. 2020 Feb 18;10(2):e034348. doi: 10.1136/bmjopen-2019-034348.

location_facility:
LOSQUIN André
ABALAIN-VOREUX Aurélie
MAHE Gwénaëlle
POINOT Anne
LE GOFF Delphine
BEURTON-COURAUD Lucas
BODIN Bénédicte
LE DUFF Nicolas
CAM Françoise
SIMON Benjamin
AUFFRET Jean François


title: Multicentre Double-blind Randomized Clinical Trial Assessing Efficacy and Safety of Exenatide in the Treatment of Hypothalamic Obesity After Craniopharyngioma Therapy

acronym: CRANIOEXE

summary:
This hypothalamic obesity is associated with serious metabolic and psychosocial consequences.

The purpose of the study is to compare the change of body weight after 6 months treatment with a lifestyle intervention + exenatide compare to the one after the same lifestyle intervention+ placebo in adults patients suffering from a hypothalamic obesity due to treatment of craniopharyngioma.

lead_sponsor: University Hospital, Bordeaux

location_facility:
Hôpital Bicêtre
CHU de Lyon
CHU de Grenoble
CHU d'Angers
APHM
Hôpital Cochin
Hôpital Européen Georges Pompidou
CHU de Toulouse
CHU de Brest
Hôpital Haut-Lévêque
Hôpital Pitié Salpétrière (APHP)


title: Predictive Tracking of Patient Flow in the Emergency Services During the Virus Winter Epidemics

acronym: PREDAFLU

summary:
Epidemics and infectious diseases in general, punctuate much of the activity of an emergency service. The impact of winter infections is particularly important to vulnerable populations such as infant during bronchiolitis epidemics and the elderly during seasonal influenza. Each year, these epidemic phenomena lead to disorganization of emergency services and healthcare teams by lack of anticipation and organizational measures in particular to manage the approval of emergency services for the most vulnerable populations requiring hospitalization.

For 2 years, the pediatric emergency department of St Etienne University Hospital has a decision support tool for the periods of winter epidemics. Through a retrospective analysis of Passages of Emergency summary, this tool provides an estimate of infants with bronchiolitis flow day to day, and the availability in real time of an abnormally high flow of patients to pediatric emergencies. These data can help to affirm that the epidemic begins in this hospital.

lead_sponsor: Centre Hospitalier Universitaire de Saint Etienne

location_facility: CH de Villefranche (adult emergency service)

location_facility: CHU de Saint Etienne (Pediatric service)

location_facility: CHU de Saint Etienne (adult emergency service)

location_facility: CHU de Grenoble (adult emergency service)


title: Randomized Phase II Study Assessing the Efficacy and Safety of 2 Therapeutic Strategies Combining Bevacizumab With Chemotherapy: De-escalation Versus Escalation in Patients With Non-pretreated Unresectable Metastatic Colorectal Cancer

acronym: HIGH-LIGHT

summary:
The intensity of tumour response appears to be correlated with the feasibility and the duration of a therapeutic pause or of a reduced maintenance therapy maintained until progression in patients initially controlled by so-called "induction" chemotherapy. Bevacizumab combined with cytotoxic chemotherapy (5-FU, irinotecan and/or oxaliplatin) has shown that it is possible to improve the tumour response rate and patient prognosis in 1st and 2nd lines. With a very favourable safety profile , it is an excellent candidate as induction treatment and also as maintenance treatment. Prospective data from recent trials have actually demonstrated improvement in PFS and/or overall survival with bevacizumab maintenance alone or in combination with 5FU (or capecitabine) after induction chemotherapy (FOLFIRI or FOLFOX + bevacizumab).

At the same time, the maintenance of anti-angiogenic pressure after progression in 1st line metastatic has demonstrated its benefit in terms of PFS and overall survival. Bevacizumab maintenance in 2nd line metastatic, despite progression, thus appears to be a valid strategy.

lead_sponsor: Federation Francophone de Cancerologie Digestive

location_facility: Hopital Prive Saint Gregoire - Service de Radiotherapie

location_facility: Ch de Cholet - Service Maladies de L4Appareil Digestif Du Dr Kaasis

location_facility: Centre Hospitalier de St Malo - Service Hepato-Gastro-Enterologie

location_facility: Chu de Saint Etienne-Hopital Nord - Service Hge

location_facility: Hopital Pierre Oudot - Service de Gastroenterologie

location_facility: Chu Robert Debre - Medecine Ambulatoire-Cancerologie


title: Can Nephrocheck™ Predict the Reversibility of Early, Acute Kidney Injury During Septic Shock?

acronym: AKI-CHECK

summary: Patients with septic shock in the intensive care unit have an elevated risk of developing acute kidney injury (AKI).

ReferenceCitation: Titeca-Beauport D, Daubin D, Van Vong L, Belliard G, Bruel C, Alaya S, Chaoui K, Andrieu M, Rouquette-Vincenti I, Godde F, Pascal M, Diouf M, Vinsonneau C, Klouche K, Maizel J. Urine cell cycle arrest biomarkers distinguish poorly between transient and persistent AKI in early septic shock: a prospective, multicenter study. Crit Care. 2020 Jun 1;24(1):280. doi: 10.1186/s13054-020-02984-6. Erratum in: Crit Care. 2020 Aug 4;24(1):483.

lead_sponsor: Centre Hospitalier Universitaire, Amiens

location_facility:
CH Paris-Saint Joseph
CH de Mont-de-Marsan
CH Cahors
CHU Saint-Etienne
CHU Poitiers
CH Avranches-Granville
CHU Montpellier
CH Salon-de-provence
CH Dax
CHU Amiens
CH Marc Jacquet


title: Case-control Study of the Influence of Pesticide Exposure on the Occurrence of Hypospadias in Newborns in Picardie

acronym: HYPOMECO

summary: We want to see if there is a relationship between exposure to pesticides and the occurrence of hypospade in Picard newborn .

ReferenceCitation: Haraux E, Tourneux P, Kouakam C, Stephan-Blanchard E, Boudailliez B, Leke A, Klein C, Chardon K. Isolated hypospadias: The impact of prenatal exposure to pesticides, as determined by meconium analysis. Environ Int. 2018 Oct;119:20-25. doi: 10.1016/j.envint.2018.06.002. Epub 2018 Jun 18.

location_facility:
CH Saint Quentin
Groupe Santé Victor Pauchet
CH Creil
CH Laon
CH Compiegne
CH Péronne
CH Chateau Thierry
CH Abbeville
CH Chauny
CHU Amiens
CH Senlis


title: Medical Economic Evaluation of Bilateral Allograft of Hands and Forearms

acronym: ARMEDIC

summary:
The double amputation of the forearms is a rare handicap that seriously impacts the autonomy and the quality of life of patients, social and familial exclusion, and dependence on third parties for everyday activities.

The management of these patients is nearly exclusively through the use of prostheses. Certain patients refuse this solution, or remain penalized by the absence of sensitivity , the lack of precision in movements, and body image issues related to the amputation; the double graft of hands and forearms may, in this circumstance, be the only solution.

Since January 2000, date of the first double hand graft, six bilateral grafts of hands have been performed at the Hospices Civils de Lyon. This first study reported the feasibility of the graft. The functional results obtained after the double transplant have allowed patients to recover complete autonomy for everyday activities, at the price of an immunosuppressive treatment. We have found that these very good functional results are maintained over time and, for a certain number of patients, to return to work which is a factor of social integration.

The rate of medical complications (metabolic, infectious, oncological), essentially related to the immunosuppressive treatment, is not greater to that found for other types of graft, but are considered as a limiting factor for the development of this strategy. These results are confirmed by international experience that is of the same order. Only a few rare cases of re-amputation have been reported in patients for whom the immunosuppressive treatment was discontinued or following vascular thrombosis.

A new study is required to continue this evaluation and to compare double graft to prostheses in terms costs, quality of life, usefulness, satisfaction, autonomy, and social integration. The results of this study will allow the placement of these strategies in the management of patients with double amputation of the hands and forearms.

design_allocation: Non-Randomized

location_facility: Serice de Médecine Physique et Réadaptation des patients amputés - Centre Médico-Chirugical et de Réadaptation des Massues

location_facility: Service de Rééducation et appareillage - Institut Robert Merle d'Aubigné

location_facility: Service de Médecine Physique et Réadaptation - Institut Régional de Médecine Physique et de Réadaptation

location_facility: Serice de Rééducation et Réadaptation fonctionnelles - Centre Jacques Calvé - Fondation Hopale

location_facility: Service de Médecine Physique et Réadapatation fonctionnelle - Centre de Médecine Physique et de Réadaptation La Tour de Gassies

location_facility: Serice de Rééducation et Réadaptation fonctionnelles - Centre l'Espoir

location_facility: Serice de Médecine Physique et Réadaptation - Hôpital d'Instruction des Armées Percy

location_facility: Serice de Rééducation fonctionnelle - Centre Mutualiste de Rééducation et Réadaptation fonctionnelles de Kerpape

location_facility: Serice de Rééducation et Réadaptation fonctionnelles - Hôpital Henry-Gabrielle - Hospices Civils de Lyon

location_facility: Serice de Rééducation et Réadaptation fonctionnelles - Centre Médical de Rééducation Romans Ferrari

location_facility: Service de Chirurgie de la Transplantation - Hôpital Edouard Herriot - Hospices Civils de Lyon


title: Multicenter Prospective Study Comparing KRAS, NRAS and BRAF Mutation Testing Using OncoBEAM Technique in Plasma vs Conventional Techniques in Formalin Fixed Paraffin Embedded Tissues

acronym: ColoBEAM

summary: RAS genotyping is mandatory for the prescription of anti-EGFR (epidermal growth factor receptor) therapies in patients with metastatic colorectal cancer. The standard genotyping is assessed on formalin-fixed paraffin embedded tumour tissue. This study compares RAS and BRAF genotyping results achieved in analyzing circulating plasma DNA using OncoBEAM™ technique with those achieved using the standard genotyping techniques and formalin-fixed paraffin embedded samples.

lead_sponsor: Institut de Cancérologie de Lorraine

location_facility:
CHRU Nancy
Polyclinique Courlancy Reims
CH Besançon-Hopital Jean Minjoz
Institut de Cancérologie de Lorraine
Centre Georges François Leclerc Dijon
Hopital Belle-Isle-Metz
CH Auxerre
Centre Paul Stauss
Polyclinique de Gentilly
CH Chalon Sur Saône-William Morey
CHU Reims-Hôpital Robert Debré

intervention_type: Genetic


title: ANRS EP59 CLEAC : Physiopathological Study of Immunovirological Evolution of Perinatally HIV-1 Infected Children Depending on Early (Before 6 Months) or Late (After 2 Years) Antiretroviral Therapy Introduction.

acronym: CLEAC

summary:
The study aims to define and compare the immunological characteristics (lymphocyte subpopulations, specific immunity against HIV, lymphocyte activation, inflammatory parameters) and the virological characteristics (study of viral reservoir) between 2 groups of vertically-HIV-1-infected children, between 5 and 17-year-of-age, who started cART before 6 months-of-age ("early treatment" group) or after 24 months-of-age ("late treatment" group) with an initial virologic success (HIV-1 RNA <400 copies / mL reached no later than 24 months after the start of cART), whatever the later evolution of the viremia.

Moreover, the viral reservoir will be deeply characterized in 10 children (5 patients in each group) with sustained control of the HIV-1 viremia under cART (≥ 90% of HIV-1 RNA measures <400 copies /mL): quantification of the reservoir in the lymphocyte subpopulations and study of the inductibility of the viral reservoir.

primary_purpose: Basic Science

ReferenceCitation: Frange P, Montange T, Le Chenadec J, Batalie D, Fert I, Dollfus C, Faye A, Blanche S, Chacé A, Fourcade C, Hau I, Levine M, Mahlaoui N, Marcou V, Tabone MD, Veber F, Hoctin A, Wack T, Avettand-Fenoël V, Warszawski J, Buseyne F. Impact of Early Versus Late Antiretroviral Treatment Initiation on Naive T Lymphocytes in HIV-1-Infected Children and Adolescents - The-ANRS-EP59-CLEAC Study. Front Immunol. 2021 Apr 22;12:662894. doi: 10.3389/fimmu.2021.662894. eCollection 2021.

lead_sponsor: ANRS, Emerging Infectious Diseases

location_facility: Centre Hospitalier Général- Hôpital Delafontaine


title: Impact on Anti-infectious Treatments of the Early Molecular Detection Technique Coupled With Urinary Test of Infectious Agents Responsible of Community-acquired Pneumonia of Children at Pediatric Emergencies

acronym: OptiPAC

summary:
Community-Acquired Pneumonia (CAP) of children are a recurrent pathology with multiple severity scores. The etiology is never really identified, and the initial treatment is always based on probabilistic antibiotics, in the case of an bacterial infection, and by the way, potentially severe.

Molecular tests ("multiplex") allow the simultaneous detection of a huge number of pathogenic agents, virus and bacteria, are now available.

This project is based on a new strategy of diagnostic, using a multiplex PCR with quick results, coupled to an antigenic urinary test to allow a complete, quick, etiologic diagnostic as soon as children are supported in emergency.

Children are randomized in two groups during inclusions : quick diagnostic strategy versus usual practice. Analyse will be centralized on anti-infectious treatment optimization, with the aim to better treat patients, minimize the costs, and decrease selection pressure of multi-resistant bacteria.

location_facility:
APHP - Béclère
Chu Grenoble
Chu Strasbourg
Chu Estaing
Chu Saint Etienne
Chu Reims
CHU CAEN
Chu Brest
Chu Marseille
APHP - Necker
Chu Toulouse


acronym: ROSCO-CF

title: A Phase II, Dose Ranging, Multicenter, Double-blind, Placebo Controlled Study to Evaluate Safety and Effects of (R)-Roscovitine in Adults Subjects With Cystic Fibrosis, Carrying 2 Cystic Fibrosis Causing Mutations With at Least One F508del-CFTR Mutation and Chronically Infected With Pseudomonas Aeruginosa, a Study Involving 36 CF Patients (24 Treated, 12 Controls). ROSCO-CF.

location_facility: Centre de Ressources et de Compétences de la mucoviscidose

summary:
This is a phase II, dose ranging, multicenter, randomized, double-blind, placebo-controlled study.

The aim of this study is to assess the safety of increasing doses of roscovitine administered orally for 4 cycles of 4 consecutive days (treatment "on") separated by a 3 days treatment free period (treatment "off") in adult CF subjects with Cystic Fibrosis carrying 2 Cystic Fibrosis causing mutations with at least one F508del-CFTR mutation and chronically infected with Pseudomonas aeruginosa.

This study involved 36 Cystic Fibrosis patients: 24 treated and 12 controls.


title: Multicentre, Cross-over, PRAgmatic Trial in Atopic Dermatitis Testing Long-term Control Effectiveness of New Phototherapy Regimen During Winter as an add-on Therapy, Coupled With Oral Vitamin D Supplementation vs. Placebo in a Randomised, Parallel-group Trial

acronym: PRADA

summary: Spaced phototherapy sessions during winter as add-on therapy in combination with vitamin D supplementation or not, could be beneficial to improve disease LTC in AD patients

ReferenceCitation: Droitcourt C, Barbarot S, Maruani A, Darrieux L, Misery L, Brenaut E, Adamski H, Chabbert C, Vermersch A, Weiborn M, Seneschal J, Taïeb A, Plantin P, Maillard H, Phan A, Skowron F, Viguier M, Staumont-Salle D, Nosbaum A, Soria A, Barbaud A, Oger E, Dupuy A; Groupe de Recherche sur l'Eczéma Atopique de la Société Française de Dermatologie (GREAT). A new phototherapy regimen during winter as an add-on therapy, coupled with oral vitamin D supplementation, for the long-term control of atopic dermatitis: study protocol for a multicentre, randomized, crossover, pragmatic trial - the PRADA trial. Trials. 2019 Mar 25;20(1):184. doi: 10.1186/s13063-019-3276-9.

location_facility:
Centre Hospitalier
Hôpital Morvan
Hôpital Saint André
Hôpital Trousseau
CHU de Nantes - Hôtel Dieu
APHP - Hôpital Tenon
Hôpital Pontchaillou
Hôpital Laënnec
CHR St Brieuc


acronym: REFRACT

title: Multicenter Phase II Trial of Nintedanib (Vargatef®) Plus Docetaxel in Second Line of Treatment in Patients With no Squamous Non Small Cell Lung Cancer Refractory to First Line Chemotherapy

lead_sponsor: University Hospital, Limoges

location_facility:
CH de Bretagne Sud
CHU Brest
Service de Pneumologie
CH de Beauvais
Instiut de Cancérologie
Institut Paoli-Calmettes
CHU de Limoges
AP-HM
Centre Hospitalier F. Quesnay

summary: The purpose of this study is to determine whether nintedanib (vargatef®) combined with docetaxel are effective in second line of treatment in patients with no squamous non small cell lung cancer refractory to first line chemotherapy.


title: Evaluation of a Strategy Based on the 3-month Screening Biopsy to Optimize the Immunosuppression in Renal Transplantation: the I4BiS Study

location_facility: Service de Néphrologie et Transplantation - Hôpital Saint-Louis

location_facility: Institut de Transplantation, Urologie et Néphrologie (ITUN) - CHU de Nantes

location_facility: Service de Néphrologie, Hémodialyse, Transplantations Rénales - Hôpital de la Cavale Blanche - CHU de Brest

location_facility: Service de Néphrologie - Hôpital Claude Huriez - CHU de Lille

location_facility: Service de Transplantation - Hôpital Universitaire Necker

location_facility: Service de Néphrologie,Transplantation, Dialyse I - Hôpital Pellegrin - CHU Bordeaux

location_facility: Service de Néphrologie, Transplantation et Immunologie Clinique - Hôpital Edouard Herriot - Hospices Civils de Lyon

location_facility: Unité de Transplantation Rénale - Hôpital Pasteur - CHU de Nice

location_facility: Département de Néphrologie et Transplantation d'Organes - Hôpital Rangueil - CHU de Toulouse

location_facility: Service Urgences Néphrologiques et Transplantation Rénale - Hôpital Tenon

location_facility: Service de Néphrologie et Transplantation - Nouvel Hôpital Civil - CHRU Strasbourg

summary:
Renal transplantation represents currently the best therapeutic alternative for end-stage renal failure, not only in terms of patient outcomes (better quality of life and longer survival), but also in terms of costs for the society.

Progress achieved in the last 20 years has resulted in a drastic reduction of the incidence of "classic" (i.e. clinically patent) acute cellular rejection episodes.

Unfortunately, and rather unexpectedly, this progress has had hardly any effect on the frequency of the loss of kidney transplants beyond the first year, as shown by the stagnation of grafts' half lives.

Furthermore, the use of immunosuppressant combinations that are more and more powerful has an impact on adverse effects in recipients, including an increased incidence of infections, cancers, but also metabolic complications (diabetes, osteoporosis, dyslipidemia, etc.), which are cause of significant morbi-mortality.

In an attempt to improve on these disappointing outcomes, some teams have offered to perform screening biopsies: i.e. routine biopsies at specific time points during the follow up, irrespective of graft function. Their primary interest is to allow a pathological analysis of the graft at an early stage, i.e. when potential histological lesions allow for a diagnosis but before these lesions impact on graft's function. Indeed, it has been clearly demonstrated that therapeutic adjustments intended to protect the grafts are most effective when introduced early. There is a fairly broad consensus to perform these biopsies three months and one year after the transplantation. Performing screening biopsies has led to the identification of "subclinical" forms of rejection, i.e. graft infiltration by recipient immune effectors meeting the Banff histological criteria, but without increase in creatininemia.

Assuming that about 10% of screening biopsies performed at 3 months reveal a subclinical rejection, which needs to be treated, the management strategy for the remaining 90% of patients, whose biopsies show either i) a mild inflammatory infiltrates: i.e. "borderline changes", or ii) the complete absence of immune effectors in the graft is, poorly standardized.

The investigators therefore propose to conduct a prospective randomized trial to answer these questions simultaneously by evaluating a strategy to optimize the immunosuppression of renal graft recipients based on the presence or absence of subclinical intragraft inflammatory infiltrates in the screening biopsy performed at 3 months post transplantation. Patients with borderline changes (sub-study A) will be randomized to receive a treatment for rejection (corticosteroid boluses). Patients without inflammation in their graft (sub-study B) will be randomized for corticosteroid withdrawal. Impact on graft function, progression of histological lesions and incidence of morbidity will be evaluated.


title: Non-randomised Open Label Pilot Study of Sirolimus Therapy for Segmental Overgrowth Due to PIK3CA- Related Overgrowth

acronym: PROMISE

summary:
It was found that people who have an excessive growth in one or more parts of their body and normal growth in other parts, may have a change in genes responsible for controlling cell growth. This genetic discovery identified a possible treatment for this overgrowth, called Sirolimus.

This is a pilot study, which help the investigators prepare a larger international study, which will aim to determine whether a treatment based Sirolimus is able to stop the excessive growth of one or more parties of their body in people who carry a genetic change in the PIK3CA gene (phosphatidylinosilol-3-kinase encoded by the gene PIK3CA).

lead_sponsor: Centre Hospitalier Universitaire Dijon

location_facility: CHRU de Montpellier - Hôpital Saint-Eloi

location_facility: Pôle Cardiovasculaire et Métabolique - Hôpital Larrey


title: Phase II Study Evaluating the Efficacy of the Combination of Metformin to Neoadjuvant Radiochemotherapy in the Treatment of Locally Advanced Rectal Cancer.

summary:
Metformin is an oral antidiabetic of the biguanide class derived from galega officinalis. Historical cohort of patients with diabetes have shown that diabetics on Metformin had a better chance of survival than diabetics not on Metformin. These observations have led to in vitro studies of metformin on cancer cells. It was thus demonstrated that Metformin has anti-proliferative properties.

The aim of our study is to evaluate the efficacy of metformin in combination with neoadjuvant radiochemotherapy in the treatment of locally advanced rectal cancer.

location_facility: Centre Galilée - Hôpital Privé La Louvière

location_facility: Centre Léonard de Vinci - SARL du pont Saint Vaast


title: Multicenter Validation of the Sensitivity of Theranostic ALK Rearrangement Detection by FISH Analysis and Prevalence of Escaping Mutations in Circulating Tumor Cells for the Non-invasive Management of Lung Cancer Patients

summary:
Patients eligibility to targeted therapies relies on a molecular test performed on a tumor sample collected by biopsy. This invasive procedure is associated with a relative high risk of morbidity and requires the intervention of a costly and important technical platform. Thus, inoperable patients can be deprived from potentially more efficient therapies. A "liquid biopsy" of Circulating Tumor Cells (CTCs) present in the blood and their molecular characterization is an appealing alternative to meet an urgent need for these patients. Moreover no CTC-based molecular test is currently routinely available.

The 5-year survival rate of patients with non-small cell lung carcinoma (NSCLC) is low. Recent reports demonstrated that the detection of an ALK rearrangement in the tumor tissue allows patients with late-stages NSCLC to benefit from crizotinib treatment.

However, 1) the detection of an ALK rearrangement is currently performed on small biopsies or fine-needle aspirates and can be hindered by the limited tissue quantities available. Tumor tissue is difficult to obtain in patients with advanced/metastatic lung cancer for whom surgery is rarely a component of treatment. Finding alternative and more effective means of diagnosing an ALK rearrangement are critical issues for identifying patients who may benefit from treatment with crizotinib; 2) some patients develop resistance to crizotinib due to de novo ALK mutations.

In this setting, circulating tumor cells (CTCs), which have been shown to be detectable by ISET (Isolation by Size of Epithelial Tumor Cells) method in 80% to 100 % of late stages lung cancer patients represent a non-invasive and easily accessible source of tumor material for assessing ALK rearrangement and escaping mutations in a kinetic manner. The ISET method was first published in 2000 and several independent teams have now established its high sensitivity and specificity of ISET for NSCLC. With ISET, specificity can be achieved using the same methods and criteria used by cytopathologists to diagnose solid tumors.

The high sensitivity and specificity of ISET are two essential starting points for the feasibility of this present project. Low-throughput molecular characterization of CTCs isolated by ISET has also been achieved. The remaining challenge consists in developing high-throughput ISET-based molecular tests for personalized medicine that are transferable to the clinics.

The Team 1 at the CHU de Nice and the Team 2 at the Gustave Roussy Institute have demonstrated that the detection of an ALK rearrangement in CTC isolated by ISET is feasible and consistent with results obtained in corresponding tumor tissues. In this context, the aim of this project is to obtain 1) a definitive prospective clinical validation of the use of CTC as an alternative to tumor tissue for ALK analysis-based patients stratification; 2) a proof that escaping mutations can be detected early by kinetic analysis of CTC in patients treated by crizotinib. ALK rearrangement will be prospectively investigated in CTCs isolated by ISET at diagnosis and during follow up from patients with stage IIIb/IV lung cancer and de novo mutations will be searched in patients with resistance to crizotinib. This study will provide both clinical and economic benefit to targeted treatment of patients with advanced lung cancer.

This project is strongly original as no CTC-based ALK rearrangement test has been independently validated up to now with clinical samples. The development of non-invasive theranostic test through the genetic analysis of CTCs is a clinically relevant goal for non-invasive stratification of cancer patients, avoiding morbidity related to lung biopsy and surgery. It would allow determining patient's eligibility to targeted therapies on a blood sample analysis. CTC-based ALK test could be useful to guide the choice of ALK targeted therapy in patients with lung cancer. Furthermore, developing biomarkers based on CTCs analysis would open the way to the non-invasive follow up of aggressive cancers, early detection of mutations associated with resistance to targeted therapies and tailoring treatment to a real time analysis of the evolving tumor cell populations. This test is expected to markedly improve patients' quality of life avoiding invasive diagnostic procedures.

lead_sponsor: Centre Hospitalier Universitaire de Nice

location_facility:
CHU de Nice
Centre Antoine Lacassagne
Institut arnault tzanck
Institut de Cancérologie de Lorraine
Toulouse University Hospital
Hôpital Tenon
Marseille University Hospital
Nancy university hospital
Institut Gustave Roussy
Grenoble university hospital
Centre François Baclesse


title: A Multi-centre, Non-inferiority, Randomized, Double-blind, Phase IV Study Comparing Pristinamycin (2g x 2 Per Day for 2 Days Then 1g x 3 Per Day for 5 to 7 Days) to Amoxicillin (1g x 3 Per Day) for 7 to 9 Days in Adults With Acute Community Acquired Pneumonia With a PORT Score of II or III

summary:
Primary Objective:

To evaluate the clinical efficacy of pristinamycin at a dose of 2g x 2/day for 2 days then 1g x 3/day for 5 to 7 days versus amoxicillin 1g x3 /day for 7 to 9 days, 5 to 9 days after the end of treatment.

Secondary Objectives:

To evaluate the clinical efficacy in a subpopulation bacteriologically documented at inclusion and according to procalcitonin level.

To evaluate the efficacy of treatments against pneumococcus. To evaluate the rate of relapse and mortality 30±2 days after treatment is started.

To document failures. To collect and follow up adverse events.

ipd_sharing_description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

lead_sponsor: Sanofi

location_country: France Tunisia

location_facility:
Investigational Site Number :250023
Investigational Site Number :788014
Investigational Site Number :250022
Investigational Site Number :250015
Investigational Site Number :250004
Investigational Site Number :250010
Investigational Site Number :250031
Investigational Site Number :788004
Investigational Site Number :250032
Investigational Site Number :250054
Investigational Site Number :250034
Investigational Site Number :788005
Investigational Site Number :788009
Investigational Site Number :250029
Investigational Site Number :788011
Investigational Site Number :788007
Investigational Site Number :788001
Investigational Site Number :788002
Investigational Site Number :250001


title: Comparison of Biological Features Between pN0 Triple Negative Breast Tumours With Size < or = 10 mm (pT1a/b) Versus pT1c T2 < or = 30 mm.

summary:
This is a prospective, non-randomized and multicenter study designed to compare biological features between pN0 triple negative breast cancer (TNBC) with size ≤ 10 mm (pT1a/b) versus pT1c T2 ≤ 30 mm.

All consecutive patients will be recruited by each investigator after completion of surgery. No modification of standard management according to each investigator center will be done. All patients will then be followed each year during 5 years in order to collect the following events: local and loco regional recurrence, metastatasis, second cancer, death or not and the cause.

At initial visit, a 10 mL blood sample will be collected (= study intervention) and immediately processed for serum storage; all serum samples will be stored at -80°C and may be used for the purpose of further scientific research.

A representative formalin-fixed paraffin-embedded tumor block of all 200 samples will be addressed at the Institut Claudius Regaud for central collection which will consist of one haematoxylin-eosin stained slide for central histological review, up to 15 unstained slides for DNA extraction (after microdissection), and construction of a tissue micro-array (TMA).

Extracted DNA from 100 samples (50 in each group) will then be transferred to Institut Paoli Calmettes, Marseille; extracted DNA will be subjected to array-CGH analysis in order to detect gene copy number alterations such as gains/amplifications/deletions, and to next generation sequencing (NGS; MiSeq, Illumina) using a panel of ~400 genes for mutation detection.

lead_sponsor: Institut Claudius Regaud

location_facility: Institut de Cancerologie de L'Ouest - Site Paul Papin

location_facility: Institut de Cancerologie de L'Ouest - Site Rene Gauducheau


type: Registry Identifier

title: A Phase 2 Study of XL184 (Cabozantinib) in Treating Patients With Relapsed Osteosarcomas and Ewing Sarcomas

summary: This phase II trial studies how well cabozantinib s-malate works in treating patients with osteosarcoma or Ewing sarcoma that has grown or returned (come back) after a period of improvement. Cabozantinib s-malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and may also prevent the growth of new blood vessels that tumors need to grow.

ReferenceCitation: Italiano A, Mir O, Mathoulin-Pelissier S, Penel N, Piperno-Neumann S, Bompas E, Chevreau C, Duffaud F, Entz-Werlé N, Saada E, Ray-Coquard I, Lervat C, Gaspar N, Marec-Berard P, Pacquement H, Wright J, Toulmonde M, Bessede A, Crombe A, Kind M, Bellera C, Blay JY. Cabozantinib in patients with advanced Ewing sarcoma or osteosarcoma (CABONE): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2020 Mar;21(3):446-455. doi: 10.1016/S1470-2045(19)30825-3. Epub 2020 Feb 17.

ReferenceCitation: Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14. Review.

lead_sponsor: National Cancer Institute (NCI)

location_facility: Institut de Cancerologie de l'Ouest-Rene Gauducheau


type: Other Grant/Funding Number

title: Evaluation of Treatment by Transcutaneous Electrical Nerve Stimulation (TENS) of the Posterior Tibial Nerve for Lower Urinary Tract Disorders in Parkinson's Syndrome

acronym: UROPARKTENS

summary:
Only one study has evaluated the effect of TENS in LUTD in Parkinson's syndromes. It was reported at the congress of the "Société Interdisciplinaire Francophone d'UroDynamique et de Pelvi-Perinéologie" (SIFUD-PP) in 2011 by Ohanessian et al., and comprised 6 female patients with Parkinson's disease (PD) or multisystem atrophy (MSA), with overactive bladder. Transcutaneous electrical nerve stimulation, 20 minutes daily for 6 weeks, was associated with subjective improvement of LUTD assessed with the Patient Global Impression of Improvement (PGI-I) in 5 of the 6 patients.

In view of the encouraging results of this pilot study, we hypothesize that TENS treatment may improve LUTD in patients with a Parkinson's syndrome, Parkinson's disease (PD) and multisystem atrophy (MSA).

ReferenceCitation: Castel-Lacanal E, Gamé X, Clanet M, Gasq D, De Boissezon X, Guillotreau J, Bourg V, Viala F, Rischmann P, Marque P. Urinary complications and risk factors in symptomatic multiple sclerosis patients. Study of a cohort of 328 patients. Neurourol Urodyn. 2015 Jan;34(1):32-6. doi: 10.1002/nau.22495. Epub 2013 Sep 23.

lead_sponsor: University Hospital, Toulouse

location_facility:
Clinique Saint Augustin
Pontchaillou Hospital
University Hospital
UHToulouse
Hospital Chenevier
Hospital Dubos
Uiversity hospital
Hospital Poincare
Huriez Hospital
University hospital


title: Effect of Vitamin D on Cognitive Decline of Patients With Memory Complaint

acronym: D-COG

summary: As recommended allowance of oral vitamine D are unable to ensure the recommended serum concentration of vitamine D, the purpose of this study is to show that a dose of vitamin D3 higher than the recommended allowance may slow the cognitive decline of patients with a memory complaint.

lead_sponsor: University Hospital, Tours

location_facility: CHU BREST - Hôpital de la Cavale Blanche


acronym: ADEQUATEartère

title: Effect of Advagraf on Arterial Stiffness and on Vascular Fibrosis Plasma Markers on de Novo Renal Transplant Patients

location_facility:
CHU de Caen
CHU de Rouen
CHU de Amiens
Necker
CHU de Strasbourg
CHU de Clermont-Ferrand
CHU de Toulouse
CHU de Angers
CHRU de Tours
HEGP
CHU de Rennes

summary: The purpose of this study is to compare parallel-group effects between 4 months and 12 months post-transplantation 2 values of target residual concentrations of Advagraf on vascular parameters in de novo renal transplant patients.


title: Pulmonary Rehabilitation in Fibrotic Pulmonary Sarcoidosis (Stage IV): Randomized Controlled Trial

summary:
The primary objective of the study is to assess the improvement of daily activity in subjects with Stage IV Pulmonary Sarcoidosis one year after the conduct of a pulmonary rehabilitation program.

The secondary objectives are the following:

assess the improvement of daily activity at several times : 2, 6 and 12 months after the beginning of a pulmonary rehabilitation program
assess the improvement of exercise capacity by tests used in medical practice
assess the correlation between daily activity and exercise capacity
assess the improvement of dyspnea
assess the improvement of quality of life and psychological state

primary_purpose: Prevention

ReferenceCitation: Wallaert B, Kyheng M, Labreuche J, Stelianides S, Wemeau L, Grosbois JM. Long-term effects of pulmonary rehabilitation on daily life physical activity of patients with stage IV sarcoidosis: A randomized controlled trial. Respir Med Res. 2020 Mar;77:1-7. doi: 10.1016/j.resmer.2019.10.003. Epub 2019 Oct 28.

lead_sponsor: University Hospital, Lille

location_facility: Service de Pneumologie, Hôpital Victor Provo

location_facility: Service de pneumologie, Hôpital Avicenne AP-HP

location_facility: Service de Pneumologie, Hôpital Pasteur - Pavillon H, CHU de Nice

location_facility: Service de Pneumologie, Hôpital européen Georges Pompidou. AP-HP

location_facility: Clinique des Voies Respiratoires, Hôpital Larrey

location_facility: Clinique des Maladies Respiratoires, CHRU de LILLE


title: Randomized Trial Comparing Functional Digestive Outcomes Related to Two Types of Management of Rectal Endometriosis: Continuous Hormonal Treatment and Curative Surgery

acronym: MESURE

summary:
The purpose of this study is to determine whether, in women with deep endometriosis involving the rectum and not intending to get pregnant, continuous hormonal treatment would be followed by better digestive functional outcomes than curative rectal surgery. Are included women from 35 to 50 years presenting with deep endometriosis infiltrating at least the muscular layer of the rectum and not having pregnancy intention.

The main outcome concerns the quality of digestive function 24 after the onset of the treatment, assessed using a composite variable: patient considering that digestive function is normal AND the Knowles-Eccersley-Scott-Symptom Questionnaire (KESS score) <7 AND the Gastrointestinal Quality of Life Index (GIQLI) score >100.

Secondary outcomes are: presence of severe constipation, increased frequency of daily bowel movements, anal incontinence, postoperative dysuria, Biberoglou & Behrman score, quality of life SF36 score, KESS score, GIQLI, Wexner score of anal continence, Bristol stools score, the rate of postoperative complications, medical treatment adverse outcomes, the rate of additional endoscopic and surgical procedures.

The randomization is central, once the physician asses the diagnosis, explain the study's principle and rece In the arm A, the patients received triptoreline and add back therapy by estradiol during 6 months, followed by daily intake of cyproterone acetate and add back therapy during 18 months.

In the arm B, patients are managed by rectal surgery (depending on the surgeon choice: rectal shaving, rectal disc excision or colorectal resection) followed by the prevention of recurrences by daily intake of cyproterone acetate and add back therapy during 18 months.

The number of subjects required is 78 (39 on each arm). Inclusions period is estimated at 24 months. The length of the follow up is 24 months. The patients have 8 visits in the arm A, and 7 visits in the arm B.

Eleven French tertiary referral centres will enrol patients in the trial.

lead_sponsor: University Hospital, Rouen

location_facility: Service de Gynécologie, Obstétrique et Médecine de la Reproduction CHU de CLERMONT-FERRAND Hôpital ESTAING 1 place Lucie Aubrac

location_facility: Service de Gynécologie-Obstétrique CHU de NIMES

location_facility: Service de Gynécologie-Obstétrique AP-HP Hôpital du KREMLIN BICETRE


acronym: COMARIS

title: Effect of the Combination of Methotrexate and Adalimumab on Reduction of Immunization in Ankylosing Spondylitis (COMARIS)

location_facility: Médecine polyvalente, CH de SAINT NAZAIRE

summary: The purpose of this study is to determine if association of methotrexate with adalimumab leads to decrease immunogenicity beside adalimumab alone in Ankylosing Spondylitis.


title: Clinical Benefits and Tolerance to a New Ventilatory Mode in Patients With Obesity Hypoventilation Syndrome (OHS).

summary: In 2012, it has announced the availability of the new ventilator (BiPAP- A40), which could offer potential advantages over fixed level pressure support, in particular, in patients with obesity hypoventilation syndrome (OHS). One of the key benefits of the BiPAP A40 is an innovative ventilation mode called AVAPS-AE, which automatically maintains airway patency while delivering the correct level of ventilation each user requires, whatever their body position or sleep stage. AVAPS-AE mode is also aimed to help the clinicians during the initial titration of therapy, while providing long term comfort and assuring therapy compliance. However, studies on the physiologic and clinical effects have not yet been performed. The aim of our singled-blind randomised multicentre controlled trial is to prospectively investigate the effects of BiPAP with the spontaneous/timed (S/T) or the AVAPS-AE ventilation mode over 8 weeks on sleep quality, ventilation pattern, gas exchange, symptoms, body composition, level of physical activity and health-related quality of life in OHS patients.

lead_sponsor: Association Nationale pour les Traitements A Domicile, les Innovations et la Recherche

location_facility: Centre Hospitalier Universitaire d'Angers


title: Optimization of Health Expenditure in Major Surgery: Impact of a Mixed, Clinical and Ethnographic Approach in the Model of Liver Surgery

summary: The aim of this study is to reduce the length of stay after liver surgery by taking account of objective quantitative clinical variables, subjective qualitative clinical variables and non clinical variables.

ReferenceCitation: Cauchy F, Farges O, Vibert E, Boleslawski E, Pruvot FR, Regimbeau JM, Mabrut JY, Scatton O, Adham M, Laurent C, Grégoire E, Delpero JR, Bachellier P, Soubrane O. Sensitizing Surgeons to Their Outcome Has No Measurable Short-term Benefit. Ann Surg. 2017 Nov;266(5):884-889. doi: 10.1097/SLA.0000000000002403.

location_facility:
Paoli calmette institute
Marseille Hospital
Strasbourg hospital
Beaujon University Hospital
Lille Regional Hospital
Bordeaux Hospital
Gustave Roussy institute
Paul Brousse Hospital
Saint Antoine Hospital
Lyon Hospital
Amiens North Hospital


acronym: TRIOCAPI

title: Impact of Early Targeted Ibuprofene Treatment of Patent Ductus Arteriosus (PDA) on Long Term Neurodevelopmental Outcome in Very Premature Infants (TRIOCAPI)

lead_sponsor: Nantes University Hospital

ReferenceCitation: Rozé JC, Cambonie G, Le Thuaut A, Debillon T, Ligi I, Gascoin G, Patkai J, Beuchee A, Favrais G, Flamant C, Durrmeyer X, Clyman R. Effect of Early Targeted Treatment of Ductus Arteriosus with Ibuprofen on Survival Without Cerebral Palsy at 2 Years in Infants with Extreme Prematurity: A Randomized Clinical Trial. J Pediatr. 2021 Jun;233:33-42.e2. doi: 10.1016/j.jpeds.2020.12.008. Epub 2020 Dec 9.

ReferenceCitation: Mitra S, Scrivens A, von Kursell AM, Disher T. Early treatment versus expectant management of hemodynamically significant patent ductus arteriosus for preterm infants. Cochrane Database Syst Rev. 2020 Dec 10;12:CD013278. doi: 10.1002/14651858.CD013278.pub2.

location_facility: University Hospital (AP-HP Groupe hospitalier)

summary: Very premature infants with a large ductus, selected by an early echocardiogram, will receive either ibuprofen or placebo before 12 hours of life. Follow-up will include repeated echocardiograms and cranial ultrasound at 36 hours, 14 days and 36 weeks of postconceptional age. The primary outcome will be survival without cerebral palsy at years.


title: Efficacy of Sacral Nerve Modulation in Severe Refractory Constipation

acronym: CONSTIMOD

summary: Subjects with refractory chronic constipation are offered two conventional therapeutic strategies: either medical treatment, either surgery (in the case of medication failure). Nevertheless, a procedure less invasive than surgery could be an alternative strategy: the sacral nerve modulation. This procedure consists in stimulating the nerves which control the contractions of the colon and so the defecation phenomenon. Several open trials have suggested that sacral nerve modulation may be effective in reducing constipation and related symptoms. The aim of this randomized clinical trial is to assess the efficacy of the sacral nerve stimulation in patients with constipation.

ReferenceCitation: Zerbib F, Siproudhis L, Lehur PA, Germain C, Mion F, Leroi AM, Coffin B, Le Sidaner A, Vitton V, Bouyssou-Cellier C, Chene G; CONSTIMOD study investigators. Randomized clinical trial of sacral nerve stimulation for refractory constipation. Br J Surg. 2017 Feb;104(3):205-213. doi: 10.1002/bjs.10326. Epub 2016 Oct 25.

lead_sponsor: University Hospital, Bordeaux

location_facility: Service de Chirurgie générale - CHU de Grenoble

location_facility: Service d'hépato-gastroentérologie et explorations fonctionnelles digestives - CHU de Tours

location_facility: Service de gastroentérologie - hopital nord -AP-HM

location_facility: Service d'exploration fonctionnelle digestive -Hospices Civils de Lyon

location_facility: Service de physiologie digestive, urinaire, respiratoire et sportive - CHU de rouen

location_facility: Service d'hépato-gastroentérologie - CHU estaing

location_facility: Service d'hépato-gastroentérologie et oncologie digestive

location_facility: : Clinique de chirurgie digestive et endocrinienne. Institut des Maladies de l'Appareil Digestif (IMAD


title: A Phase III Randomized, Multicenter, Two Arms Double-blind Trial Versus Placebo, Evaluating the Interest of a Dietary Supplementation With Docosahexaenoic Acid (DHA) During Chemotherapy for Metastatic Breast Cancer

acronym: DHALYA

summary: The aim of this study is to increase, by DHA-induced chemosensitization, the activity of anticancer chemotherapy in patients with a metastatic advanced breast cancer, by a nutritional approach with marin-derived PolyUnsaturated Fatty Acids (PUFA).

location_facility: Institut de Cancérologie de l'Ouest (ICO)

location_facility: Centre Hospitalier Départemental Les Oudairies

intervention_type: Dietary Supplement


acronym: PREDICTOR

title: Multi-centric Randomized Phase II Study of Pre-operative Afatinib (BIBW2992) Aiming at Identifying Predictive and Pharmacodynamic Biomarkers of Biological Activity and Efficacy in Untreated Non-metastatic Head and Neck Squamous Cell Carcinoma Patients

lead_sponsor: UNICANCER

location_facility: Institut de cancérologie de l'Ouest - Site Paul Papin

location_facility: Institut de cancérologie de l'Ouest - Site René Gauducheau

summary: The purpose of this study is to identify predictive and pharmacodynamic biomarkers of activity and efficacy of pre-operative Afatinib (BIBW2992) in untreated non-metastatic head and neck squamous cell carcinoma patients