Montbeliard

This research aims to evaluate the feasibility of combining radiotherapy, chemotherapy docetaxel, cisplatin, and 5-fluorouracil, and spartalizumab an anti-PD-1 therapy in patients with metastatic squamous cell carcinoma of the anus SCCA. Patients with metastatic or recurrent SCCA often receive systemic chemotherapy, and recent studies have shown that taxane-based regimens like modified DCF mDCF can be effective. This study explores adding immunotherapy and radiotherapy to improve treatment outcomes and understand resistance mechanisms. The treatment involves multiple phases. Phase 1 includes delivering 8 Gy radiotherapy to target lesions. Phase 2 consists of combined mDCF chemotherapy every two weeks for 8 cycles alongside spartalizumab given intravenously every 4 weeks. Phase 3 addresses residual disease through multimodal treatments such as surgery, hypofractionated radiotherapy, or radiofrequency ablation, plus chemo-radiotherapy for local disease if there is no progression. Phase 4 provides maintenance treatment with spartalizumab every 4 weeks for up to 12 months from enrollment. Participants will undergo various assessments including CT and PET scans, blood sample collection for immune monitoring and circulating tumor DNA analysis at multiple time points, and regular clinical evaluations. Researchers will measure progression-free survival at 1 year as the primary outcome, along with response rates and overall survival over about 3 years. Safety monitoring and biomarker studies will help understand the potential combined effects of chemotherapy, immunotherapy, and radiotherapy in this patient group.

Researchers are studying how to adjust the dose of fluoropyrimidine chemotherapy based on uracilemia levels in patients with DPD deficiency who have gastrointestinal cancers. This phase II multicenter trial aims to find the best dose reduction strategy to reduce side effects while treating digestive cancers. The main question is which dose reduction is needed for patients with this enzyme deficiency. Participants will receive chemotherapy with doses adjusted according to their uracilemia level. Patients with low uracilemia <16 ngmL will get the full dose, while those with higher levels will receive varying dose reductions or random assignments between 25% and 50% reductions depending on their uracilemia range. Treatments include the FOLFOX or CAPOX chemotherapy regimens, given in cycles every 2 to 3 weeks. During the study, participants will visit the clinic every 2 to 3 weeks for checkups and tests to monitor side effects and treatment response. Researchers will measure the occurrence of serious blood and gastrointestinal toxicities after two treatment cycles and track dose adjustments, toxicity, and survival outcomes over several months and years. The study involves close monitoring of health and treatment effects for up to three years, depending on cancer stage.

Researchers are evaluating the combination of a CD4 helper T-inducer cancer vaccine called UCPVax with anti-PD-L1 therapy atezolizumab and bevacizumab in patients with unresectable hepatocellular carcinoma HCC. This randomized Phase II trial aims to determine the clinical interest and immune response effectiveness by measuring the objective response rate at 6 months. The study involves 105 patients across 10 centers and is sponsored by the Centre Hospitalier Universitaire de Besancon. Participants are assigned to one of two groups one receiving atezolizumab plus bevacizumab combined with the UCPVax vaccine, and the other receiving only atezolizumab plus bevacizumab. Atezolizumab is given intravenously at 1200 mg every 3 weeks, bevacizumab at 15 mgkg every 3 weeks, and UCPVax vaccine is administered subcutaneously at 0.5 mg with an adjuvant. Treatment continues until disease progression or unacceptable side effects occur. During the study, patients will undergo regular assessments to evaluate tumor response using mRECIST guidelines at 6 months. Researchers will also monitor overall survival, progression-free survival, and disease control rate over approximately 2 years. Safety is closely followed through monitoring for adverse events and treatment tolerance. Participants overall health, performance status, and liver function will be evaluated throughout the study period.

Colorectal cancer is one of the most common cancers in both men and women, with increasing cases each year. Early detection is vital, often starting with a stool blood test followed by a colonoscopy if positive. Due to delays in colonoscopies during the COVID-19 pandemic, researchers are exploring a blood test to quickly identify patients who need urgent care for colorectal cancer, aiming to improve treatment timing especially during times of healthcare disruption. The study involves two groups Cohort A includes 200 patients suspected of having colorectal cancer after a positive stool blood test or visible bleeding, and Cohort B includes 200 patients already diagnosed with colorectal cancer confirmed by pathology before surgery. Participants will provide blood samples before and one month after surgery, with additional stool samples collected in Cohort B. Tumor tissue from surgery will also be collected for analysis. Participants undergo blood and stool sample collections along with tumor tissue analysis to evaluate the blood tests ability to detect colorectal cancer and its correlation with disease stage. The main outcomes include measuring the blood tests sensitivity and specificity one month after surgery and around six months after inclusion. The study is sponsored by Centre Hospitalier Universitaire de Besancon and aims to enhance colorectal cancer screening and management over a long follow-up period ending in 2032.

Researchers are investigating plasma biomarkers that could help distinguish malignant pancreatic lesions from benign ones. Currently, there is no validated blood test to aid in diagnosing pancreatic cancer PDAC, and identifying biomarkers related to the tumor stroma and immune response is a key challenge. The study aims to find biomarkers associated with malignant pancreatic lesions compared to benign pancreatic conditions, ultimately developing a clinical and biological signature to improve diagnosis and treatment decisions. Participants will have a blood sample collected at the start of the study to analyze candidate biomarkers identified from previous work and potentially others. The study compares these biomarkers between patients with malignant pancreatic lesions and those with benign pancreatic lesions, including chronic or acute pancreatitis with suspected precancerous or cystic pancreatic lesions. This is an interventional study involving biological sample collection. During the study, participants will have one visit at baseline when the blood sample is taken. Researchers will evaluate the nature of the pancreatic lesionmalignant or benignbased on imaging tests like radiology and echo-endoscopy, as well as pathological analysis if available. The primary outcome is to assess the lesion status using these methods. Participants involvement is limited to this initial assessment, and the study is sponsored by Centre Hospitalier Universitaire de Besancon, with follow-up care continuing as usual.

Squamous cell carcinoma of the anus is a rare but increasingly common cancer, often linked to human papillomavirus HPV. For early-stage tumors, combined radiotherapy and chemotherapy with 5FU and mitomycin-C provide good outcomes, but advanced tumors have a poor prognosis with a high relapse rate. Researchers are studying a new approach combining induction chemotherapy with docetaxel, cisplatin, and 5FU mDCF followed by standard chemoradiotherapy to improve treatment results for locally advanced anal cancer T3-4 or N1. This is a randomized phase 3 trial comparing this new strategy to the current standard treatment. The study includes two groups one receives the usual chemoradiotherapy, which involves 33 radiotherapy sessions over 6.5 weeks combined with mitomycin-C and capecitabine chemotherapy taken on radiotherapy days. The other group starts with 4 cycles of mDCF chemotherapy given every two weeks before receiving the same chemoradiotherapy as the control group. Radiotherapy uses intensity-modulated external irradiation with a targeted boost to the tumor and involved lymph nodes. Participants will be followed after treatment with check-ups at 8 weeks, then every 4 months for two years, and every 6 months in the third year. Follow-up includes clinical exams and imaging scans CT and MRI. The main measure of success is disease-related event-free survival two years after treatment. Other outcomes include overall survival, colostomy-free survival, treatment side effects, tumor response, and quality of life. The total study duration for each participant may extend over several years including this follow-up period.

Researchers are studying patients with metastatic colorectal cancer to identify clinical and biological factors that predict how well fruquintinib works in real-world settings. The study aims to confirm survival and safety results seen in previous trials and to better understand treatment outcomes, especially in older patients aged 70 and above, who have been underrepresented in earlier research. This cohort is designed to optimize treatment pathways by pinpointing patients who may benefit most from fruquintinib. Participants will receive fruquintinib, an oral drug that targets specific blood vessel growth receptors, given as 5 mg daily for 21 days followed by a 7-day break. This cycle repeats until the cancer progresses, unacceptable side effects occur, the patient dies, or the patient chooses to stop treatment. The study includes patients treated under compassionate use or after marketing authorization in France, integrating routine clinical practice data. During the study, participants will be monitored for overall survival up to one year after starting treatment, which is the main outcome measured. Additional monitoring includes progression-free survival within the same timeframe. The study involves collecting biological samples like circulating tumor DNA and tumor tissue blocks. Safety, survival, and treatment response data will be gathered to support understanding of fruquintinibs effects in everyday clinical use. The study is expected to continue until the end of 2031.

Researchers are evaluating the effect of combining Regorafenib with metronomic chemotherapy capecitabine and cyclophosphamide and low-dose aspirin compared to standard Regorafenib treatment in patients with metastatic colorectal cancer who are resistant to chemotherapy. This phase 2 randomized trial aims to assess progression-free survival as the main outcome to better understand treatment impact in this patient group. Participants are assigned to one of two groups one receives Regorafenib alone, and the other receives Regorafenib plus metronomic chemotherapy and low-dose aspirin. Regorafenib is given 3 weeks out of every 4-week cycle, starting with a stepwise dosing schedule in the first cycle and then continuing at adjusted doses based on tolerance. The combination group receives cyclophosphamide daily for 6 months, capecitabine twice daily for 6 months, and aspirin daily until disease progression. During the study, participants undergo blood sampling for plasma and circulating tumor DNA analysis, fresh tumor biopsies at baseline and week 8, and complete quality of life questionnaires at multiple times including baseline and follow-up visits. Researchers monitor safety, treatment effects, and progression-free survival over time. The total participation duration varies depending on individual disease progression and tolerance to treatments.

Researchers are evaluating the use of regorafenib combined with metronomic chemotherapies and low-dose aspirin as a two-month induction treatment before starting standard second-line chemotherapy in patients with metastatic colorectal cancer. This open-label, randomized Phase II-III study aims to assess this combinations impact on tumor response and overall survival compared to standard chemotherapy alone. Participants in the experimental group will receive regorafenib administered three weeks out of four for two months using a dose-escalation schedule, along with continuous oral capecitabine and cyclophosphamide and daily low-dose aspirin. After this induction phase, they will proceed to standard second-line chemotherapy with bevacizumab plus either FOLFOX or FOLFIRI regimens. The control group will receive only the second-line chemotherapy. Treatments are given according to investigator practice until disease progression or unacceptable toxicity. During the study, participants will undergo regular assessments including blood samples for plasma and circulating tumor DNA, imaging scans to measure tumor response by RECIST criteria, and quality of life questionnaires EORTC QLQ-C30, CR29, EQ-5D3L. Researchers will monitor the best objective tumor response over about 14 months and overall survival up to 64 months. Safety and treatment tolerability will also be evaluated throughout the trial.

This research investigates the treatment options for patients newly diagnosed with metastatic head and neck squamous cell carcinoma. It compares the effects of adding loco-regional radiotherapy and pembrolizumab alone or combined with chemotherapy against systemic treatment alone as the first-line therapy. The study is a phase 3, randomized, open-label trial conducted across multiple centers to evaluate these treatment strategies in this patient population. Participants are randomly assigned to receive either pembrolizumab with or without chemotherapy plus radiotherapy or systemic treatment alone. Pembrolizumab is given as a 200 mg dose every three weeks until disease progression or unacceptable toxicity. Radiotherapy timing varies, starting either before the third pembrolizumab cycle or after, with specific dose schedules targeting involved tumor regions. Chemotherapy, if added, includes carboplatin or cisplatin combined with 5-fluorouracil and is administered for up to six cycles depending on radiotherapy timing and investigator decisions. Throughout the study, participants undergo regular assessments to monitor disease progression and response to treatment. Key measurements include progression-free survival, overall survival, and quality of life questionnaires collected at multiple time points up to five years. Researchers also track treatment side effects, tumor responses, and compliance. The study period extends up to eight years, with primary outcome evaluation after three years and continued follow-up for survival and safety up to five years after randomization.