Sonchamp, France

DOVIPA, a Study Evaluating Efficacy and Safety of DOstarlimab and VItamin D3 with MFOLFIRINOX in PAncreatic Cancer

Antimicrobial Therapy for Difficult-to-treat Pseudomonas Aeruginosa

Infections due to Pseudomonas aeruginosa isolates with acquired resistances to all first-line antipseudomonal beta-lactams and fluoroquinolones (difficult-to-treat isolates - DTR), pose serious therapeutical challenges, especially in critically ill and/or immunocompromised patients. Certain new beta-lactam/beta-lactamase inhibitor combinations (BL/BLI (beta lactamine/ beta lactamase inhibitor) - i.e., ceftolozane-tazobactam, ceftazidime-avibactam, imipenem-relebactam, others) and cefiderocol have shown promising results for the treatment of infections due to DTR P. aeruginosa. However, multicenter data on their real-life utilization in this indication are still scarce. The ADDICT study is a prospective, multicenter cohort study including unselected patients with DTR P. aeruginosa infection requiring definite intravenous antimicrobial therapy. The primary objective of the study is to investigate the clinical efficacy of available options (new BL/BLI, cefiderocol or older agents such as aminoglycosides and colistin) in this population. Secondary objectives are to compare the clinical and microbiological efficacy of available options in infections due to DTR P. aeruginosa with in vitro susceptibility to more than one last-resort drug, to compare the incidence of non-ecological adverse events observed with these drugs, to assess the incidence of resistance emergence under therapy and to elucidate the molecular mechanisms of resistance emergence, to assess the benefits and risks of combination therapy in this indication, to compare the acquisition rates of multidrug-resistant bacteria other than DTR P. aeruginosa, and Clostridioides difficile infection, to compare Day-28 and in-hospital all-cause mortality rates. Patients will be recruited in 60 hospital centers contributing to four French networks of research in infectious diseases and critical care (CRICS-TRIGGERSEP, ReaRezo, OutcomeRéa, RENARCI - PROMISE metanetwork). Clinical variables will be collected through an electronic case-report form. DTR P. aeruginosa isolates will be sent to the National Reference Center of Antimicrobial Resistance in P. aeruginosa for centralized analyses (extended antimicrobial susceptibility testing, MLST, whole-genome sequencing of successive isolates if resistance emergence under therapy).

Evaluating the Safety and Efficacy of the "HIFU" High-intensity Focused Ultrasound Treatment of Benign Prostatic Hyperplasia;

Impact of an Early and Extended Rehabilitation Program Combining Individually Tailored Nutrition and Physical Activities on Patient Outcomes After Invasive Mechanical Ventilation and Vasopressor Therapy in the ICU

Phase II Efficacy Study of Repotrectinib in Frail and/or Elderly Patients With ROS1-rearranged Advanced NSCLC

This is a national, multicenter, phase II, prospective, open label, non-randomized, interventional study. Frail (PS≥2) and/or elderly patients (≥70 years) with histologically/cytologically proven stage IV or stage III non-eligible to local treatment NSCLC harboring an ROS1 gene rearrangement treated by Repotrectinib (160 mg twice a day (BID), until progression or unacceptable toxicity) in first or any line.

A Phase III, Randomised Study of Adjuvant Dato-DXd in Combination With Rilvegostomig or Rilvegostomig Monotherapy Versus Standard of Care, Following Complete Tumour Resection, in Participants With Stage I Adenocarcinoma NSCLC Who Are ctDNA-positive or Have High-risk Pathological Features

The primary objective of the study is to assess the efficacy and safety of adjuvant Dato-DXd in combination with rilvegostomig relative to SoC, after complete surgical resection (R0) in participants with Stage I adenocarcinoma NSCLC who are ctDNA-positive, as determined by the Sponsor-designated ctDNA assay, or have at least one high-risk pathological feature.

Clinical and Economic Comparison of 2 Methods of Intubation Tube Fixation : AnchorFastTM Versus Current Cord Fixation

In 2022 at Hôpital FOCH, 41% of patients admitted to the intensive care unit required an orotracheal intubation tube (OIT), exposing them to the risk of developing orotracheal intubation tube (OIT), exposing them to the risk of developing ventilator-associated pneumonia (VAP). Preventing VAP involves oral hygiene and limiting tube movements, which depend on the device used to attach the OIT . The care protocol used routinely in the department uses adhesive tape and a rigid cotton haberdashery cord. This type of fixation impedes buccal access, prevents easy repositioning of the probe and is liable to cause eschar lesions. With the aim of improving the practices, the investigators took a closer look at the French recommendations. The Société de Réanimation de Langue Française (French Intensive Care Society) does not recommend a particular fixation method, but it does relay publications that shows the superiority of the AnchorfastTM device over adhesive tape fixation in terms of the incidence of pressure sores and accidental catheter mobilization. The aim of this study is to assess the benefits of using the Anchorfast device in reducing complications associated with intubation tube fixation, in terms of the rate of pressure ulcer development, the rate of intubation tube mobilization and the rate of VAP occurrence. If the hypothesis is confirmed, this project would enable the caregivers to optimize the current practice in the interests of both patients and caregivers. That's why the investigators have designed a real-life study, and will also be looking at the effect of care load on and caregiver satisfaction.

Utility of Adjusting Chemotherapy Dose & Dosing Schedule with the SALVage Weekly Dose-dense Regimen in Patients with Poor Prognostic OVARian Cancers Based on the Tumor Unfavorable Primary Chemosensitivity and Incomplete Debulking Surgery

SALVOVAR is a pragmatic open-label multicenter randomized phase III trial (ratio 1:1) comparing the efficacy of the salvage weekly dose-dense regimen with those of the continuation of the same standard regimen as given during neo-adjuvant period. The randomization will be stratified on the main clinical prognostic factors assumed to impact the efficacy of the assessed arms and the overall survival: 1. Bevacizumab: planned administration: Yes, vs No 2. BRCA mutation: planned administration: Yes, vs No/Unknown 3. KELIMTM strate within unfavorable KELIM subgroup: very unfavorable < 0.7, vs moderately unfavorable [0.7-1.0[ The trial will be pragmatic, as it aims at confirming the superiority of the adjusted chemotherapy compared to the continuation of the standard chemotherapy in routine clinical practice, in a population of ovarian cancer patients close to the real-life clinical activity with few selection criteria.

FIRST-NEC (GFPC 01-2022) - Combination of Durvalumab With Etoposide and Platinum

Large-cell neuroendocrine carcinomas (LCNECs) of the lung are lung tumors (2%) included with small-cell lung cancers (SCLCs) in the subgroup of pulmonary neuroendocrine tumors of high-grade malignancy. Histopathological diagnosis of LCNEC is difficult, with a confirmation rate of only 70-80% after centralized expert-pathologist review. The prognosis of advanced LCNECs is poor, with overall survival (OS) of 8-10 months. The platinum-based regimen is the current recommended first-line treatment for advanced LCNECs in analogy with that given for SCLCs. The previous pivotal GFPC 03-02 trial demonstrated the efficacy of first-line platinum-etoposide in advanced LCNECs with a median Progression-Free Survival (PFS), OS and 1-year PFS of 5 months, 7.7 months and 15% respectively. The GFPC 03-2017 trial has recently reported that 75% of the tumor samples of LCNEC express programmed cell death protein-ligand-1 (PD-L1) in immune infiltrating tumor cells (ICs), and PD-L1 expression on ICs has been previously correlated with clinical efficacy of Immune Checkpoint Inhibitors (ICI) in Non-small Cell Lung Cancer. Numerous retrospective studies have also suggested ICI efficacy against LCNECs with significantly prolonged OS observed in ICI-treated LCNEC patients. Recently, the prospective NIPINEC study results demonstrated second-line nivolumab-ipilimumab efficacy against LCNECs. Moreover, at ESMO 2022, the NICE-NEC prospective phase II study on LCNECs of digestive origin found an impressive efficacy of first-line triplet platinum-etoposide-ICI with a median OS of 13,9 months, and 44 % of long survivor patients (OS>18 months). Finally, the CASPIAN trial demonstrated the superiority of the combination of durvalumab with platinum-etoposide compared to chemotherapy alone in patients with SCLCs, with an acceptable toxicity profile. Therefore, within the network of GFPC centers, the investigators propose a prospective, multicenter, open-label, phase II study with an external control arm (ESME database), that aims at evaluating the efficacy and safety of the combination of durvalumab with platinum-etoposide chemotherapy as first-line treatment in patients with an advanced LCNECs.

Ursodeoxycholic Acid (UDCA) as a Neuroprotective Adjuvant Treatment to Rhegmatogenous Retinal Detachment Surgery