Grosse Point Woods, Michigan

PARa-aOrtic LymphAdenectomy in Locally Advanced Cervical Cancer

Dupilumab Step-down Strategy to Maintain Remission in Adult and Adolescents Patients With Atopic Dermatitis

For both groups: At inclusion visit : - Patient information and signature of consent form - Randomisation - Previous medical history - Clinical exam - Recording ADCT, EASI, IGA, NRS pruritus, DLQI or CDLQI, EQ-5D-5L Weekly during 12 months (by patients on https://hestia.chu-nantes.fr) : - Self-assessment of ADCT - Date of dupilumab injections - Batch number of dupilumab - Amount of topical corticosteroids Visits at M4, M8 and M12 will be performed for : - Clinical exam - Recording secondary end points (EASI, IGA, NRS pruritus, DLQI or CDLQI, EQ-5D-5L) and adverse events - Collect out-of-pocket expenses (M4 and M12).

Feasibility Study of Early Return-home After Colorectal Surgery Using a SENSIUM® Vital Parameter Monitoring Device

Optimisation Strategy for Emergency Tracheal Intubation

Several studies have reported positive impact of some interventions on the tracheal intubation-related complications incidence. Providing bag face-mask ventilation between medication administration and initiation of laryngoscopy significantly reduced the number of peri intubation hypoxemia episodes. The use of a non-depolarizing (rocuronium) paralytic agent instead of succinylcholine is associated with less post-intubation complications occurrence. Finally, use of a tracheal tube introducer (GEB) as an aid for intubation in emergency patients with at least one prognostic factor of difficult laryngoscopy has been shown to facilitate intubation. Assessment of a strategy combining these three interventions to reduce intubation related morbidity in emergency situations has never been assessed. It is expected that the combination of these interventions will drastically reduce the morbidity associated with emergency intubation. The strategy assessed will associate rocuronium use as paralyzing agent to facilitate intubation, bag mask ventilation before intubation and GEB use at first intubation attempt in all patients. The emergency physician in charge of the patients will record out-of hospital outcomes immediately after the out-of-hospital period. Intra-hospital data will be retrieved from the patient's medical record on the 28th day after inclusion.

Assessment of the Efficacy and Safety of Alpelisib (BYL719) in Pediatric and Adult Patients with Megalencephaly-CApillary Malformation Polymicrogyria Syndrome (MCAP)

This study consists of a screening period up to 90 days, a first double-blind, placebo-controlled period of 6 months, followed by an open label period of alpelisib treatment, to reach a 24-month duration of treatment for all patients. The study will enroll 18-40 years old adults and 2-18 years old paediatric patients. Eligible patients will be randomized in a 1:1 ratio for the first period (alpelisib or placebo). A first assessment will be performed at 6 months. Patients completing this first period will enter the open label period, and either start alpelisib if they were on placebo, continue at the same dose if responders, or increase dose if not responders (dose increase only possible for children of 5 years old and over), and if no unacceptable toxicity occurs. Patients will be followed monthly in local centres, and centrally assessed (clinical, biological, neuropsychological and functional evaluation) at baseline and every 6 months. Patients will be evaluated by volumetric MRI at baseline and at 24 months. Participant may be discontinued from treatment with alpelisib earlier due to unacceptable toxicity, confirmed disease progression, death, and/or any other reason at the discretion of the investigator or the participant.

Physical Activity Return After Popliteal Artery Entrapement Syndrome Surgery

French Observational Study of Patients with Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma in Real-World Settings

Chronic lymphocytic leukemia (CLL) is the most frequent form of leukemia in the Western World. The disease is characterized by the accumulation and proliferation of mature, monoclonal, CD5+ B-cells with specific immunophenotype in the peripheral blood (above 5x109/L), bone marrow and secondary lymphoid organs. Small lymphocytic leukemia (SLL) is characterized by similar tumor cells but without increased lymphocyte count. In Europe, CLL has been identified as the second most frequent hematological malignancies after multiple myeloma (Eurocare 5 study) and its standardized incidence in the world has been estimated to be 4/100000 person-years for men and 2.1/100000 person-years for women. In France, 4674 new cases have been observed in 2018 (FRANCIM). A proportion of patients can initially be monitored only while others with symptomatic disease at diagnosis or during follow-up require therapies. The management of these patients have considerably changed over the last decade. Indeed, beyond chemo-immunotherapy, multiple targeted therapies have been approved on the basis of phase 2 and randomized phase 3 clinical trials and have subsequently been used in daily practice. The management of patients with SLL is similar to that of those with CLL. In addition to therapeutic advances, the advent of new sequencing technologies has also identified CLL genetic features that are now being incorporated in patient routine evaluation. Conventional chemo-immunotherapy (CIT) has been the long-standing option for CLL patient without TP53 disruption and different regimens have emerged depending on patient comorbidities (fludarabine-cyclophosphamide-rituximab, FCR; bendamustin-rituximab, BR; GA101-chloraminophene, G-CLB). These regimens fail to be effective in patients with TP53 disruption and alternative strategies are proposed for them. The CLL therapeutic panel is now enriched by oral kinase inhibitors targeting the B-cell receptor signaling. The Bruton's tyrosine kinase inhibitors (BTKi) have been shown to provide prolonged response, even in cases where CIT usually failed, such as patients harboring TP53 disruption. In relapsed/refractory patients, median PFS with the BTKi ibrutinib is 44 months. In the frontline setting, ibrutinib has recently been shown to result in superior PFS and less infectious complications than standard CIT regimens. The advent of the BCL2 (B-cell lymphoma 2) inhibitor venetoclax has recently added another option for the treatment of CLL patients. BCL2 is an antiapoptotic molecule governing mitochondrial apoptosis and is strongly expressed in CLL cells. Inhibiting BCL2 with venetoclax as monotherapy led to 79% response rate in the relapse/refractory setting. Combining venetoclax to rituximab demonstrated better PFS than bendamustine-rituximab in relapsed/refractory patients. However, these treatment approaches also come with new challenges that are difficult to-address in phase 3 clinical trials and that deserve larger scale studies and longer follow-up. The emergence of drug resistance, the changes of safety profiles to deal with in routine practice and the observance of these orally administered drugs are emerging as new concerns. How these compounds change the incidence of typical CLL complication such as Richter transformation, immune cytopenias and infections remains to be determined. A growing body of concerns is also raising regarding the unlimited administration of some of this the compounds (costs, resistance, tolerance). Finally, the optimal order of use of these drugs is unknown. The advent of the BCL2 (B-cell lymphoma 2) inhibitor venetoclax has recently added another option for the treatment of CLL patients 11,12. BCL2 is an antiapoptotic molecule governing mitochondrial apoptosis and is strongly expressed in CLL cells. Inhibiting BCL2 with venetoclax as monotherapy led to 79% response rate in the relapse/refractory setting. Combining venetoclax to rituximab demonstrated better PFS than bendamustine-rituximab in relapsed/refractory patients12. However, these treatment approaches also come with new challenges that are difficult to-address in phase 3 clinical trials and that deserve larger scale studies and longer follow-up. The emergence of drug resistance, the changes of safety profiles to deal with in routine practice and the observance of these orally administered drugs are emerging as new concerns. How these compounds change the incidence of typical CLL complication such as Richter transformation, immune cytopenias and infections remains to be determined. A growing body of concerns is also raising regarding the unlimited administration of some of this the compounds (costs, resistance, tolerance). Finally, the optimal order of use of these drugs is unknown. Primary objective : Setting a prospective cohort of real-world CLL/SLL patients with symptomatic disease in order to evaluate medical practices and their change and representativity over time. Secondary objectives : Overall survival and long-term toxicity, Response and PFS at each line of therapy, Impact of therapeutic trajectories on patient outcome, Representativity of the studied population

Testing Immunotherapy for Patients With Liver Cancer and Moderately Altered Liver Functions

The primary objective is to assess efficacy of anti-PD1 (in terms of Objective Response Rate [ORR] based on Best Overall Response across all time-points as defined by RECIST v1.1) in the Child-Pugh B / ALBI grade 1/2 population. Secondary objectives are : - To assess safety of anti-PD-1 - To assess efficacy in terms of: - Objective Response Rate based on best overall response across all time-point according to mRECIST and iRECIST tumor response evaluation - Overall survival (OS) - Progression-free survival (PFS) - Time to progression (TTP) - To assess Quality of Life according to EORTC QLQ-C30 and HCC-18. In order to confirm the eligibility of patients, a clinical examination, biological blood tests, ECG, CT scan and a urine or blood pregnancy test for women of childbearing age will be performed. A quality of life questionnaire will be administered to patients. Patients will also be asked to agree to a full eye examination by an ophthalmologist prior to the start of treatment to determine that there is no risk of worsening the patient's visual acuity with treatment with tislelizumab. After enrolment in the study, the patient will be required to visit the hospital every 3 weeks to receive intravenous treatment for up to 2 years. Once the treatment is completed, the patient will be seen at follow-up visits for 2 years, initially every 3 months for the first year and then every 6 months for the second year. Assessment of tumour response by CT or MRI will be done after the start of treatment at weeks 9, 18, 27, 54 and every 12 weeks until disease progression and throughout the treatment period. Tumour assessment by CT or MRI will be performed 2 years after the start of treatment or upon disease progression. Patients will be asked to consent to the use of a collected tumour sample, as well as to the collection of blood samples, for future scientific research which includes, but is not limited to, the detection of DNA, RNA and protein biomarkers. An independent Study Monitoring Board (DSMB), with expertise and experience in the pathology, and without direct involvement in the conduct of the study, will be set up specifically to ensure optimal safety monitoring during the early phase of the study and the feasibility of at least 2 treatment injections (6 weeks from inclusion), an early stopping rule has been defined for the first 20 patients included. This method was chosen for the evaluation of serious adverse events (SAEs), which may occur relatively early in this trial. A high frequency of occurrence may necessitate early termination of the trial.

Durvalumab Maintenance After Thoracic Chemoradiotherapy in Frail Small Cell Lung Cancer Patients Whose Disease is Limited to the Thorax

Small Cell Lung Cancer (SCLC) is a rare tumor, accounting nowadays for 10-15% of all new lung cancer diagnosis. Approximately one third of patients present with limited disease (LD-SCLC) confined to the chest with a median survival from 18 to 24 months and a 5-year survival rate between 20% and 25%. A platinum-based chemotherapy combined with etoposide and a concurrent thoracic radiotherapy represents the standard of care for LD-SCLC treatment with a median PFS of 12 months. However, sequential radiotherapy may be preferable for patients with poor performance status or having comorbidity predisposing to a worst tolerability. Clinical evidence supports the immunogenicity of SCLC and the involvement of immune activity in SCLC development and prognosis. Several immune checkpoint inhibitors got the approbation in first and further lines for the advanced SCLC in the last decade. The most important results have been achieved in the first-line setting for patients receiving a combination of platinum - etoposide chemotherapy and an anti-PD1/PDL-1 inhibitor compared to chemotherapy alone. However, despite these were the first positive results after a while in this setting, the modest absolute benefit showed (3 months) have to be taking into account. The possibility to enhance the immunotherapy efficacy in SCLC field with the radiotherapy administered as part of the standard treatment for a LD-SCLC seems to be a great opportunity. In the PACIFIC trial, the sequential administration of durvalumab in patients with locally advanced, unresectable, stage III Non-Small-Cell Lung Cancer (NSCLC) whose disease had not progressed following platinum-based concurrent thoracic CRT showed a dramatic overall survival improvement compared to placebo, with manageable toxicities. The ADRIATIC phase III trial, is currently recruiting LD-SCLC patients not progressing after the concomitant CRT (NCT03703297). Patients are randomized to receive durvalumab, durvalumab plus tremelimumab or placebo as maintenance treatment. In this trial, only ECOG PS 0-1 patients able to receive a concomitant CRT are eligible. However, in our clinical practice, LD-SCLC patients may not respect these criteria due to the aggressiveness of cancer and comorbidities. Thus, DURVALUNG study aims to evaluate the efficacy of durvalumab maintenance treatment in frail LD-SCLC patients who have not progressed following platinum-based concomitant or sequential CRT.

FXR Effect on Severe Alcohol-Associated Hepatitis (FRESH) Study

This is a Phase 2a, randomized, double-blind, placebo-controlled, dose-escalation, proof-of-concept study to evaluate the safety, tolerability, efficacy, and PK of INT-787 in participants, initially admitted to the hospital, with severe alcohol-associated hepatitis (sAH). The study aims to demonstrate and provide rationale for the selection of optimal dose(s) of INT-787 in the target population of participants with sAH. INT-787 will be evaluated for safety and tolerability prior to dose escalation. Overall efficacy, compared to placebo, will be assessed for each dose cohort. Additionally, PK measurements at various study timepoints will allow the Sponsor to better understand the systemic exposure of INT-787 and the relationship between exposure and efficacy and safety. Such insights in participants with more advanced liver disease will provide valuable information for future clinical trials of INT-787. The placebo-treated participants will provide important natural history information on outcomes in this participant population with sAH treated with supportive care. The placebo-treated participants within cohorts are meant to blind the study drug administration while the data across dose cohorts will be used in the overall analysis.