Aulnay-sous-bois, France

A Study Evaluating Platinum-Pemetrexed-Atezolizumab (+/-Bevacizumab) for Patients With Stage IIIB/IV Non-squamous Non-small Cell Lung Cancer With EGFR Mutations, ALK Rearrangement or ROS1 Fusion Progressing After Targeted Therapies

In patients with an EGFR mutation, several phase III studies comparing EGFR tyrosine kinase inhibitors (TKIs) with chemotherapy have shown a benefit of TKI over chemotherapy, with no demonstrated benefit on overall survival. After a first line of treatment with a TKI, most patients progress and are eligible according to the mechanism of progression to a TKI of 3rd generation in case of T790M resistance or chemotherapy. In patients with ALK translocation, crizotinib has been shown to be beneficial in first line compared to a platinum doublet.Despite these major advances, most patients are progressing after targeted treatments and chemotherapy and are facing the problem of anti-PD1 / PDL1 treatment.

Lung Cancer Screening in a Population Exposed to Occupational Lung Carcinogens

The good clinical practice guidelines for the surveillance of workers after occupational exposure to lung carcinogens were approved by the Haute Autorité de la Santé (French National Authority for Health) and the Institut National du Cancer (French National Cancer Institute) in December 2015 and the Recommendation R12 of these guidelines concerns the setting-up of a trial of low-dose chest computed tomography (CT) lung cancer screening in subjects occupationally exposed to lung carcinogens at high-risk of lung cancer (Expert consensus). In LUCSO study, the investigators propose to conduct, under strictly defined conditions, a feasibility study of lung cancer screening in a population defined as being at high risk of lung cancer according to these good clinical practice guidelines. This population consists of smokers, aged from 55 to 74 years, currently or previously exposed to International Agency for Research on Cancer lung group 1 lung carcinogens. The primary objective of this study is to evaluate the organization of lung cancer screening in the target population. This evaluation will focus on the following indicators: - Screening activity indicator: screening coverage rate over two years - Test quality indicator: validity of self-administered questionnaires to target the high-risk population - Examination quality indicator: lung cancer detection rate, lung cancer detection rates by stage, validity of low-dose chest CT scan - Follow-up indicator: smoking cessation rate, mortality rate The secondary objectives of the study are: - Describe the population recruited in each step of the protocol - Develop a tool to identify subjects exposed to pulmonary carcinogens and with high-risk of lung cancer - Evaluate the impact of the proposed screening programme on smoking cessation at one, two and three years. - Evaluate the social impact of the screening campaign - Conduct a cost-effectiveness analysis of the programme The proposed study will take place in multidisciplinary and specialized reference centers (SRC) in various French districts participating in the programme, to welcome patients participating. It is organized into six workpackages (WP): - WP1: Methodology - Epidemiology - WP2: Evaluation of occupational exposure - WP3: Imaging - WP4: Lung cancer follow-up strategy - WP5: Smoking cessation - WP6: Medico-economic analysis Six specialized reference centers are proposed in four different regions in order to test a potential region effect and to allow the recruitment by each SRC of about 200 to 600 new eligible subjects per year and per department according to the population and the age pyramid of each department - SRC1: Centre Intercommunal de Créteil for the Val-de-Marne (94), Seine-et-Marne (77), and Essonne (91) departments - SRC2: Bordeaux University Hospital for the Gironde (33) department - SRC3: Rennes University Hospital for the Ille-et-Vilaine (35) department - SRC4: Brest University Hospital for the Finistère (29) department - SRC5: Caen University Hospital for the Calvados (14) department - SRC6: Rouen University Hospital for the Seine-Maritime (76) department Each of these centers is voluntary and possesses the four essential prerequisites: an occupational health clinic - radiology team with specific skills in chest imaging - pulmonology team or network of pulmonologists specialized in lung cancer - smoking cessation team. In view of the complexity of this organization, it is proposed to initially test the feasibility and acceptability of the screening programme sequentially for the first two years (24 months) in two SRCs (SRC1 and SRC2): "Phase 1: 2021-2023". It is expected to extend the study to the other SRCs after two years: "Phase 2: 2023-2029". Ad hoc adjustments will be decided for the creation of SRCs in the third year on the basis of the data acquired in the two pilot departments, especially on the expected target population participation rate. Mortality will be monitored at least until 2031. The trial will be conducted in several steps: 1. Identification of subjects currently or previously occupationally exposed to lung carcinogens by a screening invitation letter sent by Departmental Cancer Screening Centers to subjects aged from 55 to 74 years. 2. Evaluation of occupational exposure to lung carcinogens 3. Evaluation of the lung cancer risk level and verification of eligibility 4. Screening procedure: Chest CT scans will be performed by centers specialized in chest imaging 5. Lung cancer follow-up when an abnormality suggestive of lung cancer is demonstrated.

Status Epilepticus in the Critically Ill Patients

Screening for Individual Susceptibility Factors to Immersion Pulmonary Edema

Evaluation of the Relevance of Pharmacogenetics in the Prescription Off Antidepressants in a Military Population

Study Comparing the Standard Administration of IO Versus the Same IO Administered Each 3 Months in Patients in Response After 6 Months of Standard IO

Immunotherapy (IO) is a rapidly expanding treatment for multiple metastatic cancers with improved survival for certain cancers. For currently approved immunotherapies such as PD-1 / PD-L1 inhibitors and anti-CTLA-4, the rhythm and duration of treatment are recommended until disease progression or unacceptable toxicity. However, the optimal duration of these treatments is currently unknown. No major dose-dependent effect of anti-PD-1 have been observed and whether the frequency of infusion of IO could improve response or maintain efficacy. Moreover, phase I studies have shown that saturation of the target (PD-1 or PD-L1) can persist far beyond the serum half-life of the IO and 3-monthly infusions of an anti-PD-1 antibody could potentially generate the same level of activity as infusions administered every 2 weeks. In silico modeling studies have suggested that alternate scheduling with IO couldn't compromise the efficacy of the treatment. Indeed, prolonged half-lives of IO drugs, time-varying clearance plus plasma concentrations far above the threshold associated with maximal target-engagement, suggest that the rhythm of administration of IO could be slowed down. Without substantial international data for responding patients, apart metastatic melanoma in complete response, patients and physicians are afraid of stopping treatment, by fear of relapse. Over-treatment with IO may be toxic and inefficient. The rising cost of cancer care in the era of immunotherapy is of great concern for public and private payers around the world. Chronic administration has important consequences for patients and health systems, with multiple medical visits and the risk of chronic, progressive and sometimes fatal toxicities induced by immunotherapy. This is a pragmatic and strategic study challenging the routine practice which compares for the first time in a randomized phase III study, the standard administration of IO versus the same agent administered each three months in patients with metastatic cancer in partial or complete response after 6 months of standard IO ( except melanoma in CR). If our hypothesis of non-inferiority of PFS with a reduced dose intensity of IO is verified, this could replace standard treatment and have a positive medico-economic impact, allowing, on the one hand, a reduction of the costs associated with the treatment and the toxicity, and on the other hand, an increase of the patients' quality of life.

Study of Diagnostic Biomarkers of Acute Acoustic Trauma

Impact of Hyperoxia and Involvement of the Immune System in Diving Accident

Rifabutin Versus Rifampicin for Treatment of Staphylococcal PJI Treated With DAIR

ADT +/- Darolutamide in de Novo Metastatic Prostate Cancer Patients With Vulnerable Functional Ability (PEACE6-Vulnerable)

This is a Phase III, international, multicentre, randomised, double-blinded placebo controlled trial, evaluating the efficacy and safety of ADT +/- darolutamide in castration-naïve de novo metastatic prostate cancer patients with vulnerable functional ability who have not elected for docetaxel or other androgen receptor pathway inhibitors. The study plans to enroll 300 patients who will be randomized (1:1) to receive either: (i) Experimental arm: ADT + darolutamide 600 mg po bid, or (ii) Control arm: ADT + placebo po bid. Response to treatment will be assessed according to the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria (Scher, 2016). Treatment will be continued until radiographic disease progression. Treatment may also be terminated at the initiative of either the patient or the investigator for any reason that would be beneficial to the patient, including: unacceptable toxicity, intercurrent conditions that preclude continuation of treatment, or patient request. Following treatment discontinuation patients will enter the follow-up period and will be monitored for up to 10 years with regards to survival status, subsequent antineoplastic treatments and the status of ongoing adverse events (AEs) and/or new investigational product related AEs.