Wadsworth

This research aims to evaluate the safety and effectiveness of increasing doses of NNC0662-0419 for adults living with obesity. The study is a phase 2 randomized trial comparing different dosing approaches of NNC0662-0419 and semaglutide, both administered by subcutaneous injection. Participants include adults with obesity who are committed to losing at least 25% of their body weight. Participants are randomly assigned to one of four groups receiving either NNC0662-0419 or semaglutide, or their matching placebos. All treatments are given by subcutaneous injection in a dose-escalation manner, meaning doses increase over time. This allows researchers to compare the safety and response to these drugs and their placebos. Throughout the study, participants are monitored for gastrointestinal side effects from week 0 to week 39. Body weight and body mass index BMI changes are also measured from week 0 to week 32. Participants will attend regular visits for dosing, safety assessments, and evaluations of weight and related health measures. The trial is expected to last until July 2027.

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 Stage IIB, IIC, or Stage III colon cancer based on the presence or absence of circulating tumor DNA ctDNA after surgery. This Phase IIIII trial explores whether ctDNA status can help guide decisions about the need for adjuvant chemotherapy and identify the optimal chemotherapy regimen for those at high risk of recurrence. Circulating tumor DNA is a promising biomarker that may detect microscopic residual cancer cells that traditional methods might miss. Participants are assigned to groups based on their ctDNA results after surgery. Those without detectable ctDNA ctDNA- may undergo serial monitoring without treatment or receive different chemotherapy regimens such as mFOLFOX6 or CAPOX for 3 to 6 months. Patients with detectable ctDNA ctDNA who have a higher risk of recurrence are randomized to receive either standard chemotherapy regimens like mFOLFOX6 or CAPOX for 6 months or a more intensive regimen called mFOLFIRINOX for 6 months. Central ctDNA testing is performed using the Signatera test to guide these assignments. During the study, participants have blood samples collected for ctDNA testing and undergo imaging scans to check for cancer recurrence. Researchers assess disease-free survival, overall survival, and chemotherapy compliance over several years. The study includes monitoring for safety and treatment effects, with follow-up planned for up to 5 years after randomization. Participants health status, laboratory tests, and tumor markers are regularly evaluated throughout the treatment and follow-up periods.

Researchers are comparing two types of radiation therapy, proton beam radiation therapy PBT and intensity modulated photon radiotherapy IMRT, to treat patients with stage I to IVA esophageal cancer. The study aims to find out whether PBT improves overall survival and causes fewer serious heart and lung side effects compared to IMRT. Additional goals include examining symptom burden, quality of life, tumor response, cost-effectiveness, hospitalization length, lymphocyte levels, and rates of treatment failures and complications. Participants are randomly assigned to one of two groups. One group receives PBT over 28 treatment sessions, five days a week for 5.5 weeks, combined with chemotherapy chosen by the patient and their doctor. The other group receives IMRT on the same schedule with similar chemotherapy options. After chemoradiation, patients may have surgery to remove the esophagus tumor if they are eligible. Throughout the study, blood samples and imaging scans PETCT or CT are collected. Participants are closely monitored during treatment and followed for up to eight years. Follow-up visits occur every 3 to 6 months for the first three years and annually thereafter. The study measures overall survival, heart and lung side effects, symptom changes, tumor response, hospitalization time, immune cell counts, and quality-adjusted life years. The study also collects biospecimens for future research on treatment complications and assesses economic factors related to each radiation therapy.

Researchers are evaluating a master screening protocol called Lung-MAP for patients with previously treated non-small cell lung cancer. This phase IIIII 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.

This trial studies adults with advanced non-small cell lung cancer NSCLC that has spread outside the lungs and has specific mutations in the EGFR gene. Researchers are comparing two treatment approaches osimertinib alone versus osimertinib combined with bevacizumab. The study aims to evaluate how these treatments affect the time patients live without disease progression and overall survival, as well as their effects on brain metastases and treatment safety. Participants are randomly assigned to one of two groups. One group receives osimertinib pills daily every 21 days, while the other group receives osimertinib daily plus an intravenous infusion of bevacizumab every 21 days. Treatment continues until disease progression or unacceptable side effects occur. During the study, participants undergo tests including echocardiography, MUGA scans, CT scans, and possibly MRI, along with blood and urine sample collection. After treatment ends, participants are followed every three months for up to 10 years to monitor disease status and survival. Researchers will assess progression-free survival, overall survival, response rates, time to brain progression, and side effects. The study includes long-term follow-up to understand the lasting effects of these treatments and to explore resistance mechanisms through tumor DNA analysis.

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 a combination therapy approach for adults with newly diagnosed multiple myeloma who are not intended for early autologous transplantation. This phase III trial compares a four-drug combination including daratumumab, bortezomib, lenalidomide, and dexamethasone to a three-drug combination of daratumumab, lenalidomide, and dexamethasone. The study aims to determine whether adding bortezomib improves overall survival and progression-free survival, examining minimal residual disease status and patient-reported outcomes related to neuropathy and quality of life. All participants first receive standard induction therapy with daratumumab administered subcutaneously on scheduled days, oral lenalidomide daily for 21 days per cycle, and oral dexamethasone on specific days, repeated every 28 days for 9 cycles. After induction, patients are randomized to either receive consolidation with bortezomib plus daratumumab, lenalidomide, and dexamethasone followed by maintenance with daratumumab and lenalidomide, or consolidation with daratumumab, lenalidomide, and dexamethasone followed by the same maintenance regimen. Consolidation cycles repeat every 28 days for 9 cycles, and maintenance cycles repeat every 28 days until disease progression or unacceptable toxicity. Participants undergo regular monitoring including imaging with PETCT scans, bone marrow biopsies for minimal residual disease assessment, and laboratory tests throughout induction, consolidation, and maintenance phases. Patient-reported outcomes on neuropathy and quality of life are collected, alongside safety monitoring for adverse events. After completing study treatment, participants are followed every 3 months for up to 2 years, then every 6 months up to 5 years, and annually up to 15 years to evaluate long-term outcomes and survival.