Cahors

Researchers are studying patients with metastatic colorectal cancer (mCRC) who have a specific BRAFV600E mutation. This rare subtype of mCRC has poor prognosis and resistance to current treatments, especially in tumors with microsatellite stability or proficient mismatch repair. The study aims to collect detailed clinical data and biological samples to better understand treatment outcomes, resistance, and survival in real-world settings. Participants will provide blood samples and tumor tissue samples to support various research goals. The study will evaluate circulating tumor DNA during different lines of metastatic treatment to predict treatment response and resistance. It will also analyze the immune environment of BRAFV600E mCRC tumors and study specific subgroups with mismatch repair deficiencies. Clinical management data will be collected to inform future therapeutic approaches. During the study, patients will be monitored regularly with blood sample collections of 30 mL at each time point. Researchers will gather information about treatments, survival, and biological markers over time. The main outcome measured is overall survival from diagnosis up to five years. Patients must be able to comply with study procedures and provide informed consent. The study aims to improve knowledge of this aggressive cancer subtype and support development of new treatments.

Psoriatic arthritis (PsA) is a type of arthritis that causes joint swelling and stiffness and is often seen in people with the skin condition psoriasis. It results from an overactive immune system attacking healthy tissue. This research aims to describe the long-term use and effectiveness of risankizumab (RZB) compared to other advanced treatments for managing PsA in everyday clinical care. The study is not conducted in the United States but will take place in about 15 countries and include between 900 and 1200 adult participants. Participants will be assigned in a 2 to 1 ratio to receive either risankizumab or other advanced therapeutic agents. The treatments will be given following usual medical guidelines, including approved dosing and indications, as determined by local regulations and professional standards. All study visits will occur during routine clinical care with no extra burden on participants. Participants will be followed and monitored for 24 months to observe treatment persistence. During the study, participants will continue their regular clinical visits without additional procedures or tests required by the study. Researchers will measure how many participants continue their prescribed treatment over the 24-month period. The study focuses on real-world treatment patterns and outcomes in patients with active PsA who have previously shown an inadequate response or intolerance to certain medications. Safety monitoring will align with routine clinical practice throughout the study duration.

Researchers are investigating a new treatment strategy for rheumatoid arthritis (RA), focusing on patients who are positive for specific auto-antibodies (ACPA) and have not responded sufficiently to first-line treatments like methotrexate or leflunomide. The study compares a sequential approach using two types of biologic drugs: first a tumor necrosis factor inhibitor (TNFi) to quickly control inflammation, followed by abatacept, a cell-targeted therapy. This Phase 3 trial aims to see if this combined method improves remission rates compared to continuing TNF inhibitors alone. All participants start with 12 weeks of treatment using a TNF inhibitor. Those showing at least a moderate improvement will then be randomly assigned to either switch to abatacept for 36 weeks or continue with TNF inhibitors for that period. If the first TNF inhibitor is not effective by weeks 24 or 36, a second TNF inhibitor may be tried. Throughout the study, participants may continue stable doses of other medications like methotrexate, leflunomide, steroids, or anti-inflammatory drugs. Participants will have regular clinical evaluations using various disease activity scores and safety assessments. Researchers will measure remission rates at 36 weeks after randomization to compare the two treatment strategies. The study involves monitoring disease control, treatment tolerance, and any medication changes over a total duration of about 48 weeks, providing insights into long-term outcomes and safety.

Researchers are investigating treatments for locally advanced anal squamous cell carcinoma, a rare but increasing cancer often linked to human papillomavirus (HPV). The study compares standard chemoradiotherapy, which combines radiation and chemotherapy with 5FU and mitomycin-C, to a new approach adding induction chemotherapy (modified DCF protocol) before the standard chemoradiotherapy. This randomized phase 3 trial aims to improve disease-related event-free survival and other outcomes such as overall survival, colostomy-free survival, treatment tolerability, response rate, and quality of life in patients with T3-T4 or N1 stage anal cancer without metastasis. Participants in the experimental group receive four cycles of induction chemotherapy (docetaxel, cisplatin, and 5-FU given every two weeks), followed by standard chemoradiotherapy consisting of 33 sessions of radiation over 6.5 weeks combined with mitomycin during weeks 1 and 5 and capecitabine taken on radiation days. The control group receives only the standard chemoradiotherapy. Radiation is delivered using intensity-modulated external irradiation (IMRT-SIB) targeting the pelvis and tumor area with specified doses. During the study, patients undergo follow-up visits starting 8 weeks after treatment, then every 4 months for two years, and every 6 months for a final year. Follow-up includes clinical exams and imaging tests such as CT and MRI. The study measures disease-related event-free survival at 2 years after treatment completion as the primary outcome. Participants must be adults aged 18 or older with measurable tumors on MRI and able to receive chemotherapy and radiotherapy, with additional health criteria assessed before enrollment.

Colorectal cancer mainly affects elderly patients, with over half of new cases in France occurring in those aged 70 or older. Adjuvant chemotherapy has shown benefits in disease-free and overall survival after stage III colon cancer surgery, but its use in elderly patients remains limited. This phase III randomized study explores whether adjuvant chemotherapy improves disease-free survival in elderly patients and which chemotherapy regimen is most effective, addressing concerns about benefits for both unfit and fit elderly patients. Participants will be divided into two groups based on a multidisciplinary evaluation including a geriatrician. One group will receive fluoropyrimidine-based chemotherapy (LV5FU2 or capecitabine), and the other will receive oxaliplatin-based chemotherapy (FOLFOX4 or XELOX). Some patients may be assigned to observation only. Treatments will begin within 12 weeks after surgery. The study also evaluates specific biological markers common in elderly tumors, such as mismatch repair deficiency. During the study, participants will undergo assessments including geriatric questionnaires and medical monitoring. Researchers will track disease-free survival over three years following the last patient's enrollment. Safety and treatment effects will be monitored, with exclusion of patients expected to live less than four years or those unable to comply with follow-up. The study aims to better understand chemotherapy benefits in an elderly population after colon cancer surgery.

Researchers are evaluating strategies to manage the withdrawal of denosumab treatment in women with postmenopausal osteoporosis. Denosumab withdrawal may cause a rebound effect, leading to increased bone turnover, loss of bone density, and a higher risk of vertebral fractures. This Phase 4 study aims to compare two approaches using zoledronate (ZOL) infusions to reduce this rebound effect and protect bone health after stopping denosumab. Participants receive an initial infusion of ZOL 5 mg six months after stopping denosumab. One group receives a second ZOL infusion only if a bone turnover marker called crosslaps reaches a certain level, indicating insufficient bone resorption control. The other group receives a standard treatment with a possible rescue second infusion at month 12 if there are signs of fractures or high risk. This open-label, randomized trial compares the effectiveness of these two zoledronate strategies over one year. During the study, participants have their lumbar bone mineral density measured after one year to assess bone health. Researchers monitor bone turnover markers like crosslaps to guide treatment in the biomarker-driven group. Safety and treatment outcomes, including fracture occurrence, are tracked throughout. Participants are involved in regular assessments to understand how well the strategies maintain bone density and reduce fracture risk after denosumab discontinuation.

Researchers are conducting a phase III, randomized, open-label, international trial to compare the effectiveness and safety of mosunetuzumab combined with lenalidomide versus an anti-CD20 monoclonal antibody plus chemotherapy. The study focuses on patients with previously untreated Follicular Lymphoma International Prognostic Index (FLIPI) 2-5 follicular lymphoma. This trial includes patients needing treatment based on disease characteristics and symptoms. It aims to assess progression-free survival and overall survival over a long-term period. Participants are divided into two groups. The experimental group receives mosunetuzumab in a step-up dosing schedule with cycles lasting from 3 to 8 weeks, combined with lenalidomide taken daily during specific cycles. The control group receives anti-CD20 monoclonal antibody with either CHOP chemotherapy or bendamustine chemotherapy over several cycles, followed by maintenance therapy lasting up to 30 months. The study disallows switching between groups. The total study duration is about 10 years, including screening, treatment, safety follow-up, and survival follow-up. During the study, patients undergo screening lasting up to 6 weeks before starting treatment. Assessments include evaluations at specific months during treatment to check response and safety. After treatment, patients are followed every 3 months for 2 years, then every 6 months for 3 years, and yearly thereafter until the study ends. Researchers monitor progression-free survival events assessed by an independent review committee. Participants are also evaluated for laboratory and heart function, and must adhere to visit schedules and protocol requirements throughout the study.

Researchers are investigating treatments for advanced metastatic adenocarcinoma of the stomach and gastro-esophageal junction, a serious cancer with low survival rates. Current treatments include chemotherapy combinations and immunotherapy, which have improved outcomes for some patients. However, when cancer progresses after these therapies, options are limited, and new approaches are needed to extend survival and maintain quality of life. This international Phase III trial (FRUQUITAS) tests whether adding fruquintinib, an anti-angiogenic drug, to the oral chemotherapy drug trifluridine/tipiracil can improve survival for patients whose cancer has continued to grow despite prior treatments. The study compares two groups: one receiving trifluridine/tipiracil alone and the other receiving trifluridine/tipiracil combined with fruquintinib. Trifluridine/tipiracil is given orally twice daily on days 1 to 5 and days 8 to 12 of a 28-day cycle, repeated until disease progression or unacceptable side effects. Fruquintinib is taken orally once daily for 21 days of a 28-day cycle, also continued until progression or toxicity. This combination aims to block the tumor's blood supply while providing chemotherapy. The trial evaluates if this approach extends overall survival compared to chemotherapy alone. Participants will be adults with metastatic adenocarcinoma who have received two or three previous treatment lines. They will undergo regular assessments including tumor evaluations per RECIST criteria, blood tests to monitor organ function, and safety checks. Researchers will measure overall survival up to 18 months after starting treatment. The study involves ongoing monitoring for side effects and treatment tolerance, with participation lasting until disease progression, unacceptable toxicity, or withdrawal. Biological samples may also be collected for further research, and informed consent is required before enrollment.