Wilkesboro

Researchers are evaluating treatments for patients with BRAF-V600 mutant melanoma that has spread to the brain. This phase II trial compares two combinations encorafenib, binimetinib, and nivolumab versus ipilimumab and nivolumab. The study aims to determine which approach is more effective at shrinking and controlling brain metastases, and it also examines survival, response rates, and treatment safety. Patients are randomly assigned to one of two treatment groups. One group takes encorafenib daily by mouth, binimetinib twice daily by mouth, and receives nivolumab through an intravenous IV infusion every 28 days. The other group receives nivolumab IV every cycle and ipilimumab IV over 30 minutes during the first four cycles, with cycles repeating every 21 days initially, then every 28 days. Treatment continues unless disease worsens or side effects become unacceptable. Participants undergo brain MRI scans before enrollment and throughout the study to assess tumor response using specific criteria. After completing treatment, patients are followed every six months for two years, then yearly up to three years. The study collects tissue, blood, spinal fluid, and stool samples for future research. Researchers monitor progression-free survival as the main outcome, along with overall survival, response rates, and treatment side effects.

Researchers are comparing two chemotherapy combinations for treating advanced, unresectable, or metastatic HER2 negative adenocarcinomas of the esophagus, gastroesophageal junction, and stomach. This phase III trial evaluates modified FOLFIRINOX fluorouracil, leucovorin calcium, oxaliplatin, and irinotecan with or without nivolumab versus modified FOLFOX fluorouracil, leucovorin calcium, and oxaliplatin with or without nivolumab. Chemotherapy drugs act to stop tumor growth by killing cells or stopping division, and immunotherapy with nivolumab may affect the immune system to hinder tumor growth and spread. Participants are randomized into two groups one receives mFOLFIRINOX plus nivolumab as clinically indicated, and the other receives mFOLFOX plus nivolumab as clinically indicated. Treatments are administered intravenously. Throughout the study, participants undergo magnetic resonance imaging MRI, computed tomography CT scans, and may provide blood samples. Nivolumab is given as needed based on clinical assessment during the trial. Participants will be monitored up to 2 years from randomization for overall survival, with secondary measures including progression-free survival, response rates, duration of response, adverse events, and patient-reported outcomes collected at baseline and during treatment cycles. Safety and tolerability are evaluated, and exploratory analyses include biomarker assessments such as PD-L1 combined positive score and cell-free DNA. The trial includes regular imaging and clinical assessments to track disease status and treatment effects.

Researchers are studying the relationship between low muscle mass myopenia at diagnosis and chemotherapy side effects in older adults newly diagnosed with advanced colorectal cancer. This prospective cohort study also investigates how genetic differences may influence the link between myopenia and chemotherapy toxicity, focusing on overall survival in this population receiving specific chemotherapy treatments. Participants in this observational study are older adults with metastatic colorectal cancer who are starting or recently started 5-Fluouracil 5-FU based chemotherapy, alone or combined with other drugs like oxaliplatin, irinotecan, or immunotherapy. The study groups include adults aged 60-74 years and those 75 years or older. The study tracks chemotherapy toxicities over 6 months following treatment initiation. During the study, participants will be monitored for chemotherapy toxicities graded 3 to 5 and overall survival for up to one year. Researchers will collect information through questionnaires available in English or Spanish and assess the impact of muscle mass and genetics on treatment side effects and survival. The total participation time varies, with ongoing assessments during and after chemotherapy treatment.

Researchers are evaluating the safety, side effects, and best dose of a drug called M3814 peposertib when combined with hypofractionated radiation therapy in treating patients with locally advanced pancreatic cancer that has spread to nearby tissue or lymph nodes. This phase III trial aims to see if this combination is safe, tolerable, and possibly more effective than radiation therapy alone. M3814 works by blocking enzymes needed for tumor cell growth, while hypofractionated radiation delivers higher doses over a shorter time to kill more tumor cells with fewer side effects. The study includes two phases Phase I involves dose escalation where patients receive hypofractionated radiation therapy for 5 fractions every other day over 2 weeks along with daily oral M3814 for 14 days. Phase II randomly assigns patients to either receive the same combination of radiation and M3814 or radiation with a placebo, both given under the same schedule. Blood samples, tissue biopsies, CT scans, and MRI scans are collected during screening and treatment. Participants undergo follow-up visits at 30, 60, and 90 days after completing treatment, then every 3 months for up to 2 years. Researchers monitor progression-free survival, overall survival, tumor response by imaging, and disease control. They also study pharmacokinetics of M3814 and explore gene patterns in tumor tissue and blood to understand treatment effects. The total participation may last up to 2 years including treatment and monitoring.

Researchers are evaluating whether adding stereotactic body radiation therapy SBRT to the usual treatment improves outcomes for patients with locally advanced, inoperable non-small cell lung cancer NSCLC that has spread to nearby tissues or lymph nodes. This phase III trial compares the effect of SBRT combined with conventional image guided radiation therapy IGRT, chemotherapy, and immunotherapy or targeted therapy against the usual treatment alone. The study aims to assess overall survival, progression-free survival, tumor response, lung function, quality of life, and treatment-related side effects. Participants are randomly assigned to one of two groups. In the first group, patients receive conventional IGRT and chemotherapy with drugs such as paclitaxel, carboplatin, pemetrexed, cisplatin, or etoposide during radiation, followed by immunotherapy with durvalumab or targeted therapy with osimertinib. The second group receives SBRT combined with conventional IGRT and similar chemotherapy, followed by the same immunotherapy or targeted therapy options. Both groups undergo CT andor PETCT scans during follow-up. Chemotherapy schedules vary by drug, including weekly or every 21-day dosing during radiotherapy, with consolidation treatments lasting up to one year. Throughout the study, participants undergo assessments including lung function tests FEV1 and DLCO, quality of life questionnaires, imaging scans, and monitoring for side effects using standard criteria. Follow-up visits occur every three months for the first year, every six months during years two and three, and annually thereafter, continuing for the duration of the study. Biospecimens and advanced imaging data are collected for exploratory analyses, including development of machine learning tools for radiation planning. Overall survival and progression-free survival are the primary outcomes measured up to eight years after randomization.

Researchers are evaluating whether adding stereotactic ablative radiotherapy SABR to standard immunotherapy improves outcomes in patients with metastatic or unresectable renal cell carcinoma that cannot be surgically removed. This phase II trial compares SABR combined with immunotherapy against immunotherapy alone. The study focuses on nephrectomy and radiographic progression-free survival as primary measures and also assesses safety, response rates, overall survival, and other outcomes over up to 8 years. Participants are randomly assigned to one of two treatment groups. One group receives standard immunotherapy regimens, including combinations of drugs such as nivolumab, ipilimumab, pembrolizumab, avelumab, axitinib, cabozantinib, or lenvatinib administered intravenously or orally at specified intervals. The other group receives SABR on three days over 1 to 3 weeks plus the same immunotherapy options. Imaging scans such as CT or MRI, and sometimes bone scans and blood collections, are done throughout the trial. Participants undergo regular assessments including imaging and blood tests to monitor the cancers response and safety of treatments. After treatment completion, follow-up visits occur every 6 months for 5 years, then annually for 3 more years, totaling up to 8 years of monitoring. Researchers measure outcomes such as progression-free survival, response rates, nephrectomy rates, and adverse events during this time to evaluate the treatments.