Clinical trials

The goal of this clinical trial is to identify cellular and molecular determinants of response to neoadjuvant immunochemotherapy in women aged 18 or older with early-stage triple-negative breast cancer (TNBC). The main questions it aims to answer are: * Can detailed immune profiling of the tumor and its microenvironment predict pathological complete response (pCR, RCB-0) versus partial/non-response (RCB-I, II, III) to neoadjuvant immunochemotherapy? * Are there specific immune or molecular biomarkers (e.g., TILs, CD3/8/20, FoxP3, PDL1, transcriptomic signatures) associated with progression-free survival and overall survival in this population? Researchers will compare patients achieving pCR (RCB-0) to those with residual disease (RCB-I, II, III) to determine if immune and molecular profiles can discriminate responders from non-responders and guide personalized treatment strategies.

The goal of this clinical trial is to assess the feasibility of an adapted physical activity (APA) program in adult patients (≥18 years) with primary brain tumors, regardless of tumor type, grade, treatment stage, or the presence of motor, sensory, attention, concentration, or memory deficits. The main question it aims to answer is: What is the effective adherence rate to an APA program among eligible patients with primary brain tumors? Additional questions include: * What is the observance rate (number of sessions completed, intensity achieved, and duration) during the 3-month supervised APA program? * What is the retention rate (proportion of patients completing the program and continuing APA beyond the initial period)? * What is the impact of APA on quality of life, anxiety-depression, and cancer-related symptoms (measured via QLQ-BN20, HADS, and MFI-20 questionnaires at baseline, 3, and 4 months)? Participants will: * Undergo a 3-month supervised APA program (with possible continuation beyond this period). * Use connected watches to monitor physical activity (if they accept the general conditions of use). * Complete self-questionnaires (IPAQ, BREQ-2, QPP, QLQ-BN20, HADS, MFI-20) at inclusion, 3 months, and 4 months. * Be followed for a total of 4 months after inclusion.

The aim of this clinical trial is to evaluate the efficacy of adaptive prostate Stereotatic Body RadioTherapy (SBRT), which integrates both Whole Pelvic RadioTherapy (WPRT) and dose escalation on the Dominant Intraprostatic Lesion (DIL), compared with standard radiotherapy. This will be assessed using a 5-year cost-utility analysis based on data from the clinical trial and the National Health Data System (NHDS).

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, being the third leading cause of cancer-related death worldwide, with approximately 745 000 deaths reported annually. For advanced patients, including patients with tumoral portal vein thrombosis (PVT), most treatment guidelines recommend systemic therapy, either combination immunotherapy (IO) or combination of immunotherapy and anti-angiogenic treatment for first line option. Results for PVT patients are provided in one trial with a median overall survival of 14.2 months with IO underlying the necessity to improve treatment of PVT patients. Two recent other phase 3 trials also reported positive results for different IO regimen. Selective internal radiation therapy (SIRT) using yttrium-90 (90Y)-loaded glass microspheres (TheraSphereTM) can be used for patients with early stage to locally advanced HCC including PVT patients without extrahepatic spread (EHS). TheraSphereTM is recognized and is reimbursed in France for PVT patients without EHS, since 2019.Several retrospective studies have shown promising results for PVT patients. Nowadays use of SIRT in locally advanced HCC is regaining interest based on the results of the randomized DOSISPHERE-01 study including non-operable patients, about 70% with PVT. This randomized Phase II trial using 90Y-loaded microspheres sought was noted the effectiveness of 90Y-loaded microspheres using a personalized dosimetry approach versus a standard dosimetry approach. The use of a systemic treatment as IO after a locoregional treatment with the strong local debulking effect of SIRT is logical and of interest. Indeed, the most frequent pattern of progression after SIRT is recurrence in an untreated area, including untreated liver or EHS. Patients are then usually referred to IO. Such kind of therapeutic approach, using SIRT followed by IO has already been evaluated in a phase 2 study using nivolumab after 90Y loaded resin microspheres with promising efficacy without safety deterioration. The aim of this study is to evaluate SIRT followed by IO used according to their current indications in advanced HCC patient with PVT patients and without EHS.

Treatment of intrahepatic cholangiocarcinoma (ICC) remains difficult. Many patients have unresectable tumors, and survival after resection was only slightly improved with the use of adjuvant capecitabine. One of the major prognostic factors is the resection margin, patients with invaded (R1) or narrow (\<5mm) margins having a higher risk of recurrence. Selective Internal Radiation Therapy (SIRT) with Yttrium-90 microspheres (also known as SIRT) is an interesting treatment in unresectable ICC. In a phase 2 study, the investigators showed a response rate of 39% and a disease control rate of 98%. Interestingly, 9 of the 41 patients were able to see their tumors downstages to surgery. It was also recently suggested in a retrospective study that patients resected after SIRT had a better prognosis than patients that could be operated upfront, despite less favorable initial tumor characteristics. Given the absence of validated neoadjuvant treatment, the promising activity of SIRT and chemotherapy combination in the unresectable setting, and the prognostic significance of close surgical margins, the aim of this trial is therefore to study this combination treatment in the neoadjuvant setting of resectable ICC.

Hepatocellular carcinoma (HCC) is the most common liver primary cancer with a high rate of mortality. Since the results of IMbrave150, immunotherapy have emerged as a standard of care for HCC patients advanced and/or unresectable in first line of treatment. The objective response rate was about 30%, but half of patients would present only stable disease and about 20% progressive disease. Faecalibacterium prausnitzii is one of the most abundant bacterial in human gut microbiota, around 5% of total bacteria in feces. For patients with metastatic melanoma, treated with ipilimumab, an antibody targeting CTLA-4 (Cytotoxic T-lymphocyte-associated antigen 4), patients with a baseline gut microbiota enriched with Faecalibacterium had a significantly better clinical outcomes. In patients with metastatic melanoma, the level of Faecalibacterium prausnitzi at baseline was predictive of response to anti-PD-1 (programmed death-1) or anti-CTLA-4 therapy. EXL01 is a pharmacological preparation of Faecalibacterium prausnitzii strains. Preclinical murine study suggests that the administration of EXL01 could reverse the resistance to ICI induced by antibiotics (unpublished data). We thus plan to test the concept of microbiota modification in patients treated with standard-of-care approved first-line immunotherapy for advanced HCC. We would include patients refractory to first-line treatment, and test the addition of EXL01 to standard-of-care approved first-line immunotherapy in order to reverse resistance.

HER2 gene amplification, detected in 20% to 30% of breast cancers, was a poor prognostic factor before the advent of anti-HER2 therapies. In the early 2000s, trastuzumab revolutionised the management of patients with HER2-positive (HER2+) breast cancer in the metastatic and localised stages of the disease. At the time of diagnosis of metastatic disease, 7-11% of patients have brain metastases, with (70% of cases) or without symptoms (30% of cases). In the absence of brain metastases, 30% to 50% of patients will develop brain metastases within the first two years of treatment, depending on whether the disease is hormone receptor positive (HR+) or negative (HR-). The presence of brain metastases is the most important prognostic factor. The neurological symptoms caused by the presence of these lesions, but also by the local treatments offered, affect patients' quality of life, although improvements in surgical and radiotherapy techniques have significantly reduced the need for particularly toxic whole brain radiotherapy. International guidelines do not recommend systematic brain MRI in the absence of neurological symptoms, either in the adjuvant or metastatic stages of this disease. However, there may be a role for more systematic and earlier screening for cerebral recurrence, as single cerebral recurrences without extracranial involvement are common and the new anti-HER2 agents (i.e. tucatinib, an anti-HER2 tyrosine kinase inhibitor, and T-Dxd) have shown significant objective response rates in cerebral metastases. To date, no clinical or histological prognostic factor (proliferation index, HR expression, etc.) has been used to identify a population of patients at high risk of cerebral relapse, allowing monitoring and treatment to be personalised. New tools for these indications would significantly modify our clinical practice, allowing the identification of a subpopulation at high risk of cerebral recurrence, suitable for increased monitoring and therapeutic adjustment.

The TEMPOS-GEniToUrinary Group (GETUG) study is a multicenter, medico-economic study comparing brachytherapy to SBRT in low and intermediate risk prostate cancer, particularly focused on the issue of erectile dysfunction. A total of 240 potent patients are randomized in two arms. The experimental arm consists of SBRT delivering 7.25 Gy per fraction, in five fractions, corresponding to a total dose of 36.25 Gy to the prostate. The control arm consists of brachytherapy by Iodine 125 delivering 144 Gy to the prostate. The main objective of this health economics study is to perform a cost-utility analysis of SBRT compared to "standard" Iodine 125 brachytherapy in low-risk prostate cancer, 3 years after treatment. The endpoint is the Incremental Cost-Utility Ratio (ICUR) between SBRT and brachytherapy as primary criterion, expressed in cost per quality adjusted life year (QALY) gained. Cost-effectiveness analyses are performed as secondary objective with Incremental Cost-Effectiveness Ratios (ICERs) expressed as cost per erectile dysfunction avoided and cost per Life Year Gained. A long term evaluation is also performed, including a cost-utility, cost-effectiveness and budget impact analysis at 5 years, a comprehensive assessment of the erectile dysfunction up to 5 years after treatment, an evaluation of acute and late genito-urinary (GU) and Gastro-Intestinal (GI) toxicities, and of quality of life up to 5 years after treatment. Eight patients/year/center are expected to be recruited in 2 years in about twenty participating centers. In total, to our knowledge, this study will be the first health economic evaluation which compares SBRT versus Iodine 125 brachytherapy in low risk and intermediate risk prostate cancer. Both cost-utility and cost-effectiveness analyses will also provide useful and complementary information to decision makers in order (i) to recommend the best strategy to adopt; (ii) to estimate the budget impact on the French National Health Insurance of the generalization of the cost-effective strategy. Finally, this study will allow to assess and compare accurately the erectile dysfunction after both treatment modalities.