Wilkesboro

Researchers are evaluating two treatment combinations for patients with melanoma that has spread to the brain and has a specific BRAF-V600 mutation. This phase II trial compares encorafenib, binimetinib, and nivolumab against ipilimumab and nivolumab to determine which approach better controls and shrinks brain metastases from melanoma. The study also aims to assess overall survival, response rates, treatment duration, and side effects of each regimen. Participants are randomly assigned to one of two groups. One group receives encorafenib orally once daily, binimetinib orally twice daily, and nivolumab intravenously every 28 days. The other group receives nivolumab intravenously and ipilimumab intravenously during the first four cycles, with cycles every 21 days initially, then every 28 days thereafter. Treatment continues unless the disease worsens or side effects become unacceptable. After treatment ends, participants have follow-up visits every six months for two years, then yearly until three years after starting the study. During the trial, participants undergo brain MRIs to monitor tumor response using standardized criteria. Imaging, tumor tissue, spinal fluid, stool, and blood samples are collected for research. Safety and effectiveness are carefully assessed through scans, physical exams, lab tests, and side effect monitoring. Progression-free survival up to three years after randomization is the main outcome. Participants remain in the study for about three years with periodic evaluations to track their health and disease status.

Researchers are evaluating two chemotherapy treatments, mFOLFIRINOX and mFOLFOX, with or without the immunotherapy drug nivolumab, for advanced, unresectable, or metastatic HER2 negative adenocarcinoma of the esophagus, gastroesophageal junction, and stomach. This phase III trial aims to determine whether adding irinotecan to the usual FOLFOX regimen improves overall survival and other outcomes such as progression-free survival, response rates, and treatment tolerability. The study also explores biomarkers like PD-L1 combined positive score and cell free DNA to understand treatment effects better. Participants are randomly assigned to one of two treatment groups. One group receives fluorouracil, leucovorin calcium, oxaliplatin, and irinotecan (mFOLFIRINOX) with nivolumab as needed, while the other group receives fluorouracil, leucovorin calcium, and oxaliplatin (mFOLFOX) with nivolumab as needed. All drugs are given intravenously. Throughout the trial, patients undergo MRI and CT scans and may provide blood samples for additional testing. During the study, participants are closely monitored for overall survival for up to two years after randomization. Researchers assess safety, side effects, and patient-reported outcomes to evaluate treatment tolerability. The trial also tracks progression of disease and response to therapy using imaging and other clinical evaluations. Participation includes regular imaging, blood collection, and completing questionnaires to help understand the impact of these treatments.

Researchers are studying how low muscle mass, known as myopenia, affects chemotherapy side effects and overall survival in older adults newly diagnosed with advanced colorectal cancer. The study also looks at how genetic differences might influence the link between myopenia and chemotherapy toxicity. This research focuses on patients receiving 5-Fluorouracil (5-FU) based chemotherapy, sometimes combined with other drugs or immunotherapy. The study includes older adults with metastatic colorectal cancer who are starting or have recently started first-line treatment with 5-FU chemotherapy, alone or combined with oxaliplatin, irinotecan, or immunotherapy. Capecitabine is also allowed. The study tracks patients over time to observe chemotherapy side effects and survival, but there are no specific investigational treatments or devices involved. Participants will be monitored for chemotherapy toxicities, especially those graded 3 to 5, for up to 6 months after starting treatment. The study collects data on muscle mass, genetic factors, and treatment outcomes to understand how these affect chemotherapy side effects and survival. Participants must be able to complete questionnaires in English or Spanish and provide consent to join the study.

Researchers are evaluating the safety, side effects, and best dosage of a new drug called M3814 (peposertib) combined with hypofractionated radiation therapy in treating patients who have locally advanced pancreatic cancer that has spread to nearby tissues or lymph nodes. This phase I/II trial aims to determine if adding M3814 to radiation therapy can improve progression-free survival compared to radiation therapy alone. The study also explores various secondary objectives, including tumor response, overall survival, disease control, and genetic markers that may predict treatment response. During the phase I portion, patients receive hypofractionated radiation therapy given in 5 doses every other day over two weeks, along with daily oral doses of M3814 for 14 days, provided there is no disease progression or unacceptable side effects. In phase II, patients are randomly assigned to two groups: one group receives the same radiation plus M3814, and the other group receives radiation plus a placebo, both over the same schedule. The study includes tissue biopsies, blood sample collections, and imaging scans such as CT and MRI to monitor the disease and treatment effects. Participants will be followed up regularly after treatment completion, with visits at 30, 60, and 90 days, then every three months for up to two years. Researchers measure outcomes such as the maximum tolerated dose of M3814, progression-free survival, and response rates using imaging. Safety and tolerability are closely monitored through clinical assessments and laboratory tests throughout the study. This trial helps to better understand the combination treatment's effects on locally advanced pancreatic cancer.

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 that has spread to nearby tissues or lymph nodes. This phase III trial compares SBRT combined with conventional image guided radiation therapy (IGRT), chemotherapy, and immunotherapy or targeted therapy versus the usual treatment alone. The usual chemotherapy involves drugs like cisplatin, carboplatin, paclitaxel, nab-paclitaxel, pemetrexed, and etoposide. Immunotherapy with durvalumab or targeted therapy with osimertinib is also given after chemotherapy, aiming to interfere with tumor growth and spread. Patients are randomly assigned to one of two treatment groups. In the control group, patients receive conventional IGRT with weekly or every-3-week chemotherapy followed by immunotherapy with durvalumab or targeted therapy with osimertinib. In the experimental group, patients receive SBRT to the primary tumor plus conventional IGRT to nodal metastases, combined with the same chemotherapy and consolidation therapies as the control group. Radiation therapies are delivered with precision to minimize damage to healthy tissue. Follow-up imaging with CT and/or PET/CT scans are performed during and after treatment. Participants undergo physical exams, imaging scans, pulmonary function tests, and quality of life assessments before, during, and after treatment. Researchers monitor overall survival and progression-free survival for up to eight years. They also track tumor response, local control, treatment side effects, lung function changes, and patient-reported outcomes. Follow-up visits occur every three months for one year, every six months for years two and three, and yearly thereafter to assess long-term effects and safety.

Researchers are evaluating whether adding stereotactic ablative radiation therapy (SABR) to standard immunotherapy improves outcomes for patients with metastatic renal cell cancer that cannot be removed by surgery. This phase II trial compares the combination of SABR and immunotherapy to immunotherapy alone. Immunotherapy drugs include monoclonal antibodies like nivolumab, ipilimumab, avelumab, pembrolizumab, and targeted therapies such as axitinib, cabozantinib, and lenvatinib. The study aims to assess kidney removal and radiographic progression-free survival as the main outcome. Participants are randomly assigned to one of two groups. One group receives immunotherapy alone, with different drug combinations given intravenously or orally as chosen by the doctor. The other group receives SABR treatment delivered in three sessions over 1 to 3 weeks alongside the same immunotherapy regimens. SABR uses high-precision radiation to target tumors with fewer doses and less damage to healthy tissue. Both groups undergo regular scans such as CT or MRI and may have bone scans and blood samples taken throughout the trial. After completing treatment, patients are followed up every six months for five years, then yearly for three more years. Researchers monitor outcomes including tumor response, disease progression, safety, side effects, survival, and biomarkers from tissue and blood samples. The study also evaluates effects on blood vessel tumors and the response of non-irradiated tumors. Total participation may last up to eight years with ongoing assessments to understand long-term benefits and risks.