Wadsworth

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 evaluating how to best recommend chemotherapy for patients with colon cancer based on the presence or absence of circulating tumor DNA (ctDNA) after surgery. This Phase II/III trial focuses on patients with Stage IIB, IIC, or Stage III colon adenocarcinoma who have undergone tumor removal. The study aims to use ctDNA status to better predict the risk of cancer recurrence and guide decisions about adjuvant chemotherapy. Participants will be assigned to different treatment groups based on their ctDNA status after surgery. Patients without detectable ctDNA will undergo serial ctDNA monitoring without immediate treatment or receive standard chemotherapy regimens such as mFOLFOX6 or CAPOX for varying durations. Patients with detectable ctDNA will receive either standard chemotherapy or intensified regimens like mFOLFIRINOX. Treatments involve intravenous and oral chemotherapy drugs given over several cycles spanning weeks to months. Throughout the study, participants will have ctDNA testing using the Signatera test and be monitored for disease-free survival, overall survival, and recurrence up to five years after randomization. Safety and treatment adherence will also be tracked. Regular imaging and laboratory tests will assess disease status and organ function. The study may include re-randomization for patients who develop positive ctDNA during monitoring. Total involvement may last several years with follow-up for long-term outcomes.

Researchers are evaluating how well proton beam radiation therapy compares to intensity modulated photon radiotherapy in treating patients with stage I-IVA esophageal cancer. This phase III trial aims to determine whether proton beam therapy improves overall survival and reduces serious heart and lung side effects compared to photon radiotherapy. The study also examines symptom burden, quality of life, treatment costs, and disease control outcomes. Participants are randomly assigned to one of two treatment groups. One group receives proton beam therapy over 28 sessions in 5.5 weeks alongside chemotherapy with drugs like carboplatin, paclitaxel, or fluorouracil-based regimens. The other group receives intensity modulated photon radiotherapy on the same schedule with similar chemotherapy options. Both groups undergo blood sample collection and imaging scans such as PET/CT or CT during treatment. Surgery to remove the esophagus is considered within 4 to 8 weeks after therapy if feasible. Throughout the study, participants will have follow-up visits every 3 to 6 months for three years, then annually afterward. Researchers will monitor survival, heart and lung toxicities, immune cell counts, symptom changes, hospital stays, and cancer progression. Patient-reported outcomes and quality-of-life measures are collected, along with biospecimens for future biomarker analysis. This comprehensive monitoring will help assess the benefits and risks of each radiation approach over time.

Researchers are evaluating a master screening protocol called Lung-MAP for patients with previously treated non-small cell lung cancer. This phase II/III trial aims to develop a genomic screening method for large cancer populations and assign participants to appropriate sub-studies based on specific cancer biomarkers. The goal is to compare new targeted therapies designed to block cancer growth or spread with standard care, including sub-studies for patients not eligible for biomarker-driven treatments. The study involves screening patient specimens to determine eligibility for various biomarker-driven or non-matched sub-studies within the Lung-MAP umbrella protocol. This is a screening study without direct interventions; instead, patients are assigned to different treatment sub-studies, each operating independently. The protocol also includes an optional ancillary study evaluating attitudes about the return of somatic mutation findings suggestive of germline mutations. Participants provide tumor tissue for biomarker testing, including molecular profiling and PD-L1 analysis, and may submit fresh biopsies and blood samples for circulating tumor DNA testing. Researchers will monitor screening success rates up to three years and collect patient and physician feedback on genetic findings. Participation involves signing informed consent, providing smoking history, and possibly completing surveys. The study duration and assessments vary depending on sub-study assignment and patient progression.

Researchers are evaluating the combination of bevacizumab and osimertinib versus osimertinib alone as an initial treatment for patients with advanced non-small cell lung cancer (NSCLC) that has spread beyond the lungs and has specific mutations in the EGFR gene. This phase III trial aims to understand if adding bevacizumab, which inhibits blood vessel growth to tumors, can control cancer longer and improve survival compared to osimertinib alone, which blocks EGFR involved in tumor cell growth. Participants are randomly assigned to one of two groups. One group receives daily oral osimertinib every 21 days, while the other group receives the same osimertinib dose plus an intravenous bevacizumab infusion every 21 days. Treatment continues until disease progression or unacceptable side effects occur. During the study, patients undergo various imaging tests such as echocardiography, multigated acquisition scan, computed tomography, and possibly magnetic resonance imaging, along with blood and urine sample collections. After treatment ends, patients are followed every three months for up to 10 years to monitor their health and disease status. The main outcome measured is progression-free survival, tracking the time until the cancer worsens or death occurs. Secondary outcomes include overall survival, response rates, and effects on central nervous system progression. Safety is also assessed through adverse event monitoring. This long-term follow-up helps researchers understand the lasting effects of the treatments.

This research aims to compare the effects of regional radiotherapy versus no regional radiotherapy in women with low-risk breast cancer who are receiving usual care. The study focuses on women with node-positive or T3N0 breast cancer who have undergone breast-conserving surgery or mastectomy, to see if avoiding regional radiotherapy works as well at preventing the cancer from returning. Participants receive either whole breast irradiation with or without regional radiotherapy to lymph nodes after surgery, or no regional radiotherapy following mastectomy or breast-conserving surgery. The study involves random assignment to these treatment groups and evaluates the impact of adding or omitting regional radiotherapy as part of their care. During the study, researchers will monitor breast cancer recurrence-free interval over 9.5 years, along with other outcomes such as invasive disease-free survival, mortality, overall survival, and quality of life. Patient-reported outcomes, arm mobility, adverse events, and cost-effectiveness are also assessed. Treatment adherence, follow-up visits, and collection of tumor tissue and blood samples are part of the participant's involvement throughout the trial.

Researchers are evaluating patients with metastatic HER-2-positive breast cancer who are receiving trastuzumab-based therapy and are at risk of heart problems. The study includes two groups: one large observational group taking beta blockers, ACE inhibitors, or ARBs alongside trastuzumab, and a smaller randomized group comparing the effects of carvedilol versus no treatment. The aim is to understand the occurrence of heart issues and whether carvedilol might help prevent cardiac side effects from chemotherapy. Participants are assigned to one of three arms based on their current medications. Patients not on beta blockers, ARBs, or ACE inhibitors are randomized to either receive carvedilol orally twice daily or no study intervention. Those already taking these heart medications enter an observational arm without additional treatment. Treatment and observation continue for up to 108 weeks unless disease progression or unacceptable side effects occur. Throughout the study, participants undergo heart function monitoring with echocardiograms every 12 weeks and provide blood samples for biomarker analysis. Researchers track the time to the first sign of heart dysfunction and any cardiac events, as well as adherence to medication and side effects. The study also collects data to develop models predicting heart risk and banks samples for future research. Participant involvement may last over two years with regular assessments to monitor safety and heart health.

Researchers are evaluating treatments for adults with newly diagnosed multiple myeloma, a type of plasma cell cancer. This phase III trial compares a four-drug combination including daratumumab, bortezomib, lenalidomide, and dexamethasone to a three-drug combination without bortezomib. The study aims to find out if adding bortezomib improves overall and progression-free survival, response rates, and patient quality of life while monitoring side effects and disease markers like minimal residual disease (MRD). All participants first receive a standard induction therapy with daratumumab, lenalidomide, and dexamethasone over about 9 cycles of 28 days each. After this, patients are randomly assigned to one of two consolidation and maintenance treatments: one group receives bortezomib along with the other drugs for consolidation followed by maintenance with daratumumab and lenalidomide; the other group receives consolidation and maintenance without bortezomib. Treatments are given by subcutaneous injection or orally at specified days and cycles. Patients are followed long-term for up to 15 years after study entry. During the trial, patients undergo regular assessments including blood and urine tests, bone marrow biopsies, and imaging scans like PET/CT to measure disease status and treatment response. Patient-reported outcomes on symptoms like neuropathy and quality of life are also collected. Safety is closely monitored through adverse event reports. Follow-up visits occur every 3 months initially, then less frequently over time to track survival and health outcomes.