Charlottesville

Researchers are developing advanced four-dimensional magnetic resonance imaging 4D-MRI techniques to create detailed, moving images of the lungs and liver in adults. This imaging method produces three-dimensional movies that capture organ motion during breathing, which is important for improving radiation therapy planning for lung and liver cancer patients. The study aims to overcome challenges in current imaging methods to better target tumors that move with respiration. The study includes two main parts technical development of ultra-quality 4D-MRI in healthy volunteers and evaluation of the technique in cancer patients. This involves creating a new MRI pulse sequence and image reconstruction process to achieve high spatial and temporal resolution with minimal motion artifacts. Researchers will compare the new 4D-MRI method to existing imaging and registration techniques in both healthy volunteers and patients with lung or liver tumors undergoing radiation therapy. Participants will undergo a single imaging session lasting up to two hours involving 4D-MRI scans. Healthy volunteers and cancer patients will be assessed to measure image quality and accuracy of motion modeling. The study will monitor how well the 4D-MRI technique captures tumor movement compared to current methods. The total participation time is limited to the imaging session, with no long-term follow-up mentioned.

Researchers are evaluating the safety and effectiveness of tenapanor in adults with Chronic Idiopathic Constipation CIC. This study is a 26-week, multi-center, randomized, double-blind, placebo-controlled trial followed by a 4-week treatment-free safety follow-up period. It aims to compare three different doses of tenapanor with a placebo taken twice daily to assess their impact on constipation symptoms. The study includes a 2-week screening period to confirm eligibility, followed by a 26-week randomized treatment period where patients receive either 5 mg, 25 mg, or 50 mg of tenapanor twice daily, or a matching placebo. Patients record their constipation symptoms daily in an electronic diary. After the treatment period, there is a 4-week safety follow-up without treatment to monitor any adverse effects. Participants will have regular visits every 2 to 6 weeks for safety checks including medical assessments, vital signs, ECG, and lab tests. Their symptom diaries will be reviewed throughout the study. The main outcome measured is the durable complete spontaneous bowel movements response at 12 weeks. Secondary outcomes include changes in bowel movement frequency, stool consistency, and straining. The total study duration is approximately 32 weeks including all phases.

Researchers are studying treatments for locally advanced or metastatic colorectal cancer mCRC that cannot be removed by surgery and has a specific KRAS G12C gene mutation. This trial aims to evaluate if adding the targeted therapies calderasib and cetuximab to the standard chemotherapy regimen mFOLFOX6 can provide better outcomes compared to mFOLFOX6 with or without bevacizumab. The study focuses on the safety and tolerability of these combinations and whether they can help people live longer without their cancer growing or spreading. Participants will be assigned to one of two groups. One group will receive calderasib orally, cetuximab every two weeks, and mFOLFOX6 chemotherapy including oxaliplatin, leucovorin or levofolinate calcium, and 5-fluorouracil every two weeks. The other group will receive mFOLFOX6 chemotherapy with or without bevacizumab every two weeks, based on the investigators decision. Treatments will continue until certain stopping criteria are met. During the study, participants will be monitored for side effects and treatment tolerance, with regular assessments of cancer progression. Researchers will measure outcomes such as dose-limiting toxicities, adverse events, progression-free survival, and overall survival. Quality of life will also be evaluated through questionnaires. The study may last up to several years, with monitoring continuing for safety and effectiveness throughout the treatment period and follow-up.

Researchers are investigating new treatments for extensive-stage small cell lung cancer ES-SCLC, a type of lung cancer that has spread widely within the lungs or to other parts of the body. This study evaluates the combination of two study medicines, gocatamig and I-DXd ifinatamab deruxtecan, with or without standard chemotherapy and immunotherapy. The research aims to understand the safety and tolerance of these combinations and whether they can shrink or eliminate tumors in people with ES-SCLC. Participants are assigned to one of several treatment groups. Some receive gocatamig and I-DXd during maintenance after completing standard chemotherapy and immunotherapy, while others receive these study medicines during both induction and maintenance phases. Additional groups receive gocatamig and I-DXd followed by gocatamig and atezolizumab, or standard treatment with carboplatin, etoposide, and atezolizumab followed by atezolizumab maintenance. Treatments are given intravenously and continue until disease progression or other study-specified criteria. During the study, participants will have regular assessments to monitor safety, side effects, and treatment response, including scans to measure tumor size and laboratory tests to evaluate drug levels and immune response. The study will track adverse events, treatment tolerability, and cancer control over up to approximately 58 months. Participants health status and responses to the treatments will be closely observed throughout this period, with periodic evaluations to understand long-term effects and outcomes.

Researchers are evaluating a new vaccine called V118C designed to help prevent pneumococcal disease, an infection caused by Streptococcus pneumoniae bacteria. This clinical trial focuses on infants and toddlers to assess how safe and well-tolerated V118C is in young children. The study is a Phase 1, randomized, double-blind trial comparing V118C with an existing vaccine called PCV20. The study is divided into two stages. Stage 1 involves toddlers aged 12 to 15 months who have already received a primary series of three doses of PCV vaccine they will receive a single dose of either V118C or PCV20. Stage 2 includes infants starting at approximately 2 months old who will receive four doses three infant doses plus one toddler dose of either V118C or PCV20. All doses are given as 0.5 mL intramuscular injections. Participants will be monitored closely for adverse events immediately after vaccination, as well as for up to 12 months postvaccination. Researchers will collect blood samples to measure immune responses to the vaccines. They will track both injection site and systemic reactions, serious adverse events, and medically attended events. The study aims to understand both safety and immune response profiles of V118C compared to PCV20 over the course of the dosing schedules and follow-up periods.

Researchers are exploring new treatments for women with relapsed high-grade serous ovarian cancer, which is a fast-growing cancer starting in ovarian cells, the lining of the belly, or fallopian tubes. The study evaluates raludotatug deruxtecan R-DXd, a type of antibody drug conjugate, combined with other therapies, to understand safety, tolerability, and cancer response. This includes women with platinum-sensitive and platinum-resistant recurrent ovarian cancer who have had prior treatments. The study has two parts Part 1 involves gradually increasing doses of R-DXd combined with chemotherapy drugs like carboplatin, paclitaxel, bevacizumab, or pembrolizumab to find a recommended dose. Part 2 uses this recommended dose to further assess treatment effects. Participants receive intravenous infusions every three weeks, with chemotherapy cycles lasting up to about four months and pembrolizumab up to two years. The combinations vary depending on cancer sensitivity and treatment history. Participants undergo regular treatment visits where cancer response and side effects are monitored. Tumor tissue samples are collected before treatment. Researchers track adverse events, dose-limiting toxicities, and how long the cancer responds to treatment. The study lasts up to approximately three years, allowing for long-term safety and effectiveness assessments, with ongoing evaluation of participants health throughout the trial.

Researchers are investigating new treatments for metastatic cervical cancer, which is cancer that has spread beyond the cervix, the lower part of the uterus. This study evaluates the safety and effectiveness of the antibody drug conjugate sacituzumab tirumotecan sac-TMT combined with pembrolizumab and bevacizumab. The goal is to find out if these treatments, given together or with some variations, help patients live longer or delay cancer progression compared to standard care. The study has two parts. In Part 1, participants receive sac-TMT, pembrolizumab, and bevacizumab together to assess safety. In Part 2, all participants first get standard induction treatment with pembrolizumab, paclitaxel, and cisplatin or carboplatin, possibly with bevacizumab. Those whose cancer does not worsen then enter maintenance treatment, where they are randomly assigned to receive either pembrolizumab alone or sac-TMT plus pembrolizumab, with optional bevacizumab. Participants are involved for up to about 20 months during maintenance treatment after up to 4 months of induction. The study monitors safety by tracking side effects and treatment discontinuations. Effectiveness is measured by progression-free survival and overall survival up to several years. Quality of life and physical functioning are also assessed through questionnaires. Treatments and evaluations occur through regular intravenous infusions and periodic monitoring visits.

Researchers are evaluating the experimental antibody COM701 to see if it can delay the progression of relapsed platinum sensitive ovarian cancer, fallopian tube cancer, or primary peritoneal cancer. The trial aims to find out if COM701, given as maintenance treatment, can slow disease progression, delay the need for new anti-cancer treatments, and to understand its safety profile in participants who have had prior platinum-containing therapies. This trial is a randomized, double-blind, placebo-controlled study where participants have a 67% chance to receive COM701 and a 33% chance to receive a placebo. The treatment is given through intravenous infusion once every three weeks. The study includes multiple sub-studies, with initial focus on COM701 alone and later evaluation of COM701 combined with other anti-cancer drugs as maintenance therapy. Participants will visit the clinic every three weeks for treatment infusion and undergo various health checks including physical exams, vital signs, ECG, blood and urine tests, and pregnancy tests if applicable. Disease response is monitored through tumor imaging by CT or MRI scans and analysis of tumor tissue samples. The main outcome is progression-free survival over up to two years, with safety monitored during and up to 90 days after treatment. The study duration and follow-up depend on individual participant progress.

Researchers are evaluating zorevunersen, an investigational antisense oligonucleotide drug, in children with Dravet syndrome, a rare and severe form of epilepsy. This Phase 3, global, multicenter, randomized, double-blind, sham-controlled study aims to assess the efficacy, safety, and tolerability of zorevunersen by measuring changes in major motor seizure frequency and other important aspects such as behavior, cognition, clinical status, and quality of life. Participants will be randomly assigned to receive either zorevunersen or a sham procedure during Treatment Period 1, which lasts about 52 weeks. Zorevunersen is given by intrathecal injection at specific doses and intervals throughout this period. After Treatment Period 1, all eligible patients enter Treatment Period 2, where everyone receives zorevunersen for additional dosing over several months. Patients who complete the study may have the chance to join an open-label extension to continue receiving the drug. During the study, participants will undergo regular assessments including seizure monitoring, behavioral and cognitive evaluations, and health-related quality of life measurements. The primary outcome is the change in major motor seizure frequency at Week 28, with secondary outcomes assessed at Week 52. Safety and tolerability are also closely monitored. Overall participation lasts through both treatment periods and possible extension, with detailed follow-up to evaluate the drugs potential for disease modification.

This research aims to evaluate if men with prostate cancer who experience hot flashes from their androgen deprivation therapy ADT will consistently wear a smartwatch to track their health data and log hot flashes. The study focuses on comparing smartwatch data with daily surveys about hot flash experiences to better understand these symptoms. The study is conducted with patients receiving ADT who report daily hot flashes and are willing to use wearable technology for monitoring. Participants will be given an EmbracePlus smartwatch and a charging device after consent and eligibility confirmation. They will be trained to use the device, including how to log hot flashes by pressing a button on the watch. The smartwatch pairs with a smartphone app to transmit biometric data and hot flash events to a cloud server for research access. Participants will wear the watch continuously for 28 days, except for charging, and receive up to four daily surveys through text message links to report their hot flash experiences. Throughout the study, participants will be monitored by the research team who will verify data collection and device use. They will receive a check-in call and complete an end-of-study survey. Researchers will measure the duration of watch wear per day, the percentage of days with self-reported hot flash events, and how well smartwatch logs match the surveys. The total participation lasts 28 days, during which biometric data and subjective hot flash reports are collected and analyzed.