Clinical trials

This phase I study is designed to establish the safety, maximally tolerated dose (MTD) and recommended phase II dose (RP2D) of the ERK inhibitor ulixertinib (BVD-523) when combined with the CDK4/6 inhibitor palbociclib.

The purpose of this study is to test the feasibility and acceptability of a multi-level, community-engaged intervention to increase access to cervical cancer screening using human papillomavirus (HPV) self-collection (HPVSC) outreach among women living in a high-risk rural county and to improve navigation for follow-up screening. A one-group intervention evaluation design will be used to pilot test feasibility and acceptability and to assess the proportion of women who return HPVSC kits and test HPV-positive. At the community level, local community-based organizations (CBOs) will serve as HPVSC kit distribution sites. At the individual level, trained community health workers will work with CBOs to support women throughout the HPVSC process, including specimen collection, kit return, result notification, and follow-up clinic-based screening for women who test HPV-positive.

This study compares changes in P16INK4A expression and plasma proteomic signatures of specific organ age pre- and post-chemotherapy in women treated with adjuvant chemotherapy for early-stage breast cancer. It aims to determine if biological and accelerated immune aging, assessed using T cells from peripheral blood, represents aging in different organs. Patients receiving chemotherapy, especially adjuvant regimens that include anthracyclines and taxanes, often experience late development of cardiac toxicity, functional loss, and cognitive decline. Comparing baseline characteristics with organ aging before therapy might identify patients at the highest risk for chemotherapy complications. For example, this is clinically significant for patients whose therapy includes taxanes or other drugs known to cause peripheral neuropathy. Identifying aging in the neurological or vascular systems before treatment might lead to changes in regimens. Determining accelerated aging in specific organs allows for investigating interventions to mitigate organ damage. For instance, identifying patients at the highest risk of cardiac aging after treatment could lead to testing the effects of exercise, senolytics, and other strategies to reduce the risk of long-term heart disease.

This study examines how virtual support can enhance well-being and survivorship in men with testicular cancer. Participants in North Carolina will be randomized into two groups: one with access to a virtual support platform and the other with access to patient educational materials only. After six months, the emotional well-being, self-efficacy, financial toxicity, and quality of life of both groups will be compared at 3 months and 6 months after baseline assessments.

The purpose of this study is to evaluate whether a novel decision support tool called PRIME (Preference Reporting to Improve Management and Experience), which combines values-elicitation with tailored feedback to patients and providers, improves patient-reported values-concordance of initial treatment decisions compared to usual care.

Brain metastases are a source of much morbidity and mortality in adults with primary solid malignant tumors. With improvements in systemic therapy that prolong survival but have limited central nervous system penetration, patients with brain metastases are at increasing risk of developing and experiencing long-term side effects from treatment of brain metastases. The overarching goal of this study is to better understand the determinants of RT-associated changes in white and gray matter function and associated neurocognitive decline.

The purpose of this study is to evaluate the persuasive effectiveness of narrative advertisements: with acted-out plots (where characters enact a vaping-related experience) versus narrative advertisements without acted-out plots and control. Using a 3-arm between-subjects randomized design, approximately 1,910 adolescents and young adults (aged 13-20) in the U.S. who vape or are susceptible to vaping will be recruited online. Participants will be randomly assigned to view video ads from one of three conditions (narrative with acted-out plots, narrative without acted-out plots, or control videos) and complete a post-exposure survey evaluating message engagement, emotional response, perceived effectiveness, and psychological reactance.

This study investigates the feasibility, acceptability, and preliminary efficacy of enCompass Humana, a social support intervention for caregivers of patients with cancer and diabetes. The enCompass program aims to improve support for these caregivers through a randomized feasibility study of a pilot-tested coaching and navigation program. Caregiver services and system-level support are essential, but successful interventions for cancer caregivers are rarely standardized or systematically disseminated. Consequently, many programs do not reach the most underserved caregivers. Challenges to implementation include substantial clinical staff involvement, lack of dissemination and implementation information, and failure to tailor interventions to rural contexts. Despite the lack of standardized supportive interventions, national reports and legislative efforts increasingly recognize the need to support caregivers. Caregivers reported unmet needs in all domains of social support, including instrumental help (e.g., in-home help, housekeeping), logistical and coordination support (e.g., food delivery, accompanying patients to appointments), information about illness and progression, emotional support, self-care guidance, and financial assistance (e.g., parking costs, lost wages). Caregivers show high interest in services but cited uncertainty and lack of strategies for accessing resources. Many are unaware of existing services. Interviews with oncology clinicians and healthcare administrators revealed similar findings: resources exist, but there is no system to match them with caregivers' needs. Preliminary data suggest the intervention improves caregiver coping self-efficacy and reduces anxiety and depression in patients. With input from stakeholders, including caregivers, patients, family caregiving experts, and clinical care experts, the study team adapted the CARING application into enCompass to mitigate structural barriers and normalize support-seeking. The long-term goal is to adapt this psychosocial support program to increase self-efficacy, support-seeking, and reduce loneliness among caregivers. It is hypothesized that enCompass will build self-efficacy and coping skills, serving caregivers throughout the patient's illness and complications.

This study evaluates the impact of neoadjuvant Programmed cell death Protein 1 (PD-1)-based treatment regimens in patients with resectable stage IIIB-M1a cutaneous or unknown primary melanoma at high risk of relapse without adjuvant therapy after definitive lymphadenectomy and irrespective of pathologic response outcome on the 2-year overall survival (OS). It was hypothesized that neoadjuvant PD1 inhibitor-based treatment without adjuvant treatment does not significantly (non-inferior) impact OS in this study patient population. Patients will be randomized to either two infusions of pembrolizumab or one infusion of ipilimumab plus nivolumab followed by a single infusion of nivolumab. Patients will undergo follow-up and restaging scans to assess event-free survival at 12 months and OS at 24 months after the first neoadjuvant treatment infusion.

This Phase II hybrid decentralized multicenter study examines the outcomes of stopping Bruton tyrosine kinase inhibitor (BTKi) therapy in patients with chronic lymphocytic leukemia (CLL) who have remained in remission for at least two years. The primary objective is to determine how long patients remain free from disease progression or death after discontinuing treatment, measured as event free survival. The study also evaluates whether stopping BTKi therapy leads to improvements in quality of life and reductions in treatment related side effects. Researchers will follow patients over time to assess if the cancer returns, whether resistance to therapy develops, and how patients feel during the treatment free period. In addition, the trial will investigate how discontinuing BTKi therapy affects immune function, including whether immune recovery occurs and infection risk decreases. Preliminary data indicate that patients may experience a treatment free interval exceeding two years after stopping therapy, with associated improvements in quality of life. By prospectively evaluating a time limited treatment strategy, this trial aims to determine whether durable disease control can be maintained off therapy while also assessing the resolution of BTKi related adverse events and changes in patient reported outcomes. Overall, the study seeks to determine whether patients can safely discontinue BTKi therapy and potentially restart treatment later if needed, thereby maintaining disease control while reducing the burden of continuous therapy.

Despite the progress in the therapy, Hodgkin's Lymphoma (HL) remains fatal for more than 15% of patients. Even in patients who are cured, the morbidity of therapy is substantial and long-lasting. New therapeutic agents are required therefore not only to further reduce mortality but also to alleviate morbidity. The majority of HL express the CD30 antigens. CD30 expression is routinely used for the diagnosis of HL. Preclinical observations support CD30 as a viable target of CAR-T therapy. This phase Ib/II study was conducted based on these observations. The purpose of this study is to determine the tolerability of ATLCAR.CD30.CCR4 cells in subjects with Hodgkin's Lymphoma and identify a recommended dose for further. This is a single-center, open-label phase Ib/II trial that uses a 3+3 design to identify a recommended phase 2 dose (RP2D) of ATLCAR.CD30.CCR4 cells in Hodgkin's Lymphoma. The phase II portion is designed to determine the PFS of ATLCAR.CD30.CCR4 in Hodgkin's Lymphoma. Subjects will be enrolled on 1 of 3 dose levels as determined by a 3+3 design. Up to 25 evaluable subjects may then be enrolled in the phase II portion of the study. Subjects may have cells procured to manufacture the ATLCAR.CD30.CCR4 cells if they meet eligibility for procurement. During the time period necessary to manufacture the ATLCAR.CD30.CCR4 cells, Subjects will be allowed to receive standard-of-care bridging therapy at the discretion of their local oncologist. Prior to cell infusion, subjects will undergo additional eligibility evaluations, and then if eligible, will undergo lymphodepletion followed by cell infusion 2-14 days later. Subjects will then be followed for 15 years as is required for studies involving gene transfer experiments.

Acute lymphoblastic leukemia (ALL) is the most common cancer in children and, along with lymphoblastic lymphoma, represents the most common group of childhood lymphoid malignancies. Survival rates have improved over the years, but many children still experience long-term side effects from treatment. These can include tiredness, weak muscles, pain, nerve problems, difficulty moving, and other physical challenges. Many children with ALL are also overweight at diagnosis, and weight gain often continues during treatment. As a result, about half of childhood leukemia survivors have a BMI at or above the 85th percentile. Treatment decisions are usually based on a child's symptoms and genetic risk factors. However, some risk factors such as physical activity can be modified. Exercise during treatment may help children feel better and may even improve survival. However, research on early symptom tracking and structured exercise during the first phase of chemotherapy is limited, uses different methods, and often does not include reliable patient-reported symptoms. Effective exercise programs for children with ALL and lymphoblastic lymphoma need to consider the child's age, treatment side effects, motivation, family support, and ways to encourage long-term behavior change. Because children spend little time in the hospital during the induction phase, a mix of in-person and virtual sessions supported by real-time Zoom instruction can make it possible to offer safe and supervised exercise at home. This study will use a guided exercise plan that includes tools to track sets, repetitions, intensity, warm-up time, and perceived exertion. These tools help with consistent monitoring and support both patients and caregivers throughout the program. Twenty children newly diagnosed with ALL or lymphoblastic lymphoma who receive standard 3-4 drug induction chemotherapy will be invited to participate. Our goal is to determine whether a 9-week hybrid exercise program, combined with weekly symptom check-ins, is practical and achievable in both hospital and home settings.

This is a multicenter, multi-arm, biomarker-stratified trial designed to evaluate biomarker-directed therapies in patients with estrogen receptor-positive/hormone receptor-negative (ER+/HR-) and triple-negative (TN) metastatic breast cancer (MBC). The trial integrates both retrospective and prospective data collection, including archival tumor tissue, medical record abstraction, and prospective tumor and blood sampling prior to initiation of protocol directed treatment. Based on biomarker subtype, participants will receive standard of care therapy. Liquid biopsy will be collected on Cycle 2 Day 1, and then liquid biopsy, imaging and clinical data will be collected at each re-staging. Treatment will continue until discontinuation for progression, toxicity or at the discretion of the treating physician.

This phase 1, single-center, open-label study explores the safety of escalating doses of chimeric antigen receptor T cells (CAR-T) cells in subjects with relapsed/refractory triple-negative breast cancer (TNBC).

This study evaluates whether the time of day when immunotherapy is given affects clinical outcomes. It includes patients eligible for PD-1 (programmed cell death protein 1) or PD-L1 (programmed death-ligand 1) inhibitor treatment who have either advanced or metastatic non-small cell lung cancer (NSCLC) or locally advanced, resectable head and neck squamous cell carcinoma (HNSCC).The study tests the hypothesis that outcomes differ based on infusion timing (morning versus afternoon). Patients are divided into two cohorts by disease type: Cohort 1 includes NSCLC and Cohort 2 includes HNSCC. Within each cohort, patients are randomly assigned to receive infusions in the morning or afternoon, using a 2:1 ratio for NSCLC and a 1:1 ratio for HNSCC. All treatment and disease assessments follow standard medical care, and outcomes such as survival and treatment response are collected from medical records. Patients will be followed for up to 2 years.

The study is a pilot test of effectiveness of communication campaign ads on interest in quitting combustible cigarettes and e-cigarettes. Over the course of 5 weeks, participants are sent ads that are designed to encourage quitting and then answer surveys.

Patients with extremity soft tissue sarcoma (STS) are at high risk of recurrence. Pre-operative radiotherapy is used to increase the safe removal of tumors and improve local control in these patients. Increasing the preoperative radiotherapy dose with standard techniques might lead to normal tissue toxicity and postoperative wound complications. GRID radiation therapy is a technique that may increases radiation dose with minimal added toxicity. It is hypothesized that GRID radiation dose will improve tumor response without increasing post-operative wound complications. While GRID has been used in many patients, there have been few formal studies to evaluate the safety and efficacy of the technique. In this study, a single priming dose of GRID will be administered to subjects with high-risk extremity soft tissue sarcoma prior to standard radiotherapy and tumor resection to determine the safety and clinical efficacy of the GRID dose. This single-arm pilot study will assess the safety of spatially fractionated grid radiation therapy (GRID) on 20 subjects with resectable extremity soft tissue sarcoma, followed by standard-of-care conventional radiotherapy (XRT) and tumor resection.

This is a single-site, non-randomized study on the outcomes of remote real-time "ePRO monitoring" in thoracic surgery patients. ePRO monitoring is a health information technology intervention comprised of delivering longitudinal electronic patient-reported outcome (ePRO) surveys (e.g., on symptoms, and physical functioning) coupled with automated provider alerts for concerning survey responses.

This is a hybrid decentralized, single-arm, interventional study designed to evaluate the impact of precision medicine navigation and reflexive expert review of next-generation sequencing (NGS) for patients with stage IV solid tumor malignancies (breast, lung, colorectal, and bladder cancers). The purpose of this study is to investigate whether intervention from a centralized precision oncology navigator and expert review of NGS results by the precision oncology pharmacist will increase ordering of Level 1/2 genome informed therapy (GIT) compared to an estimated historical rate of 15%. Secondary endpoints will assess the impact of a centralized precision oncology navigator and expert review of NGS results on enrollment in biomarker-directed clinical trials and overall survival at 2 years after return of NGS results. The study will take approximately 12 months for enrolment and 2 years of follow-up after the date of NGS results.

The goal of this study is to evaluate the effectiveness and usability of a newly developed oral anticancer agent adherence program implemented across 6 cancer clinics (two academic, two urban, and two rural). The study will include 160 adult participants with either solid tumors or hematologic malignancies who have been taking oral anticancer agents for at least six months. This study will have two groups of participants, a pre- and post-implementation group. In the pre-implementation of the program group, investigators will administer a survey to the 80 participants and gather information about their medication prior to their enrollment of the program. Similarly, 80 participants who have been enrolled into this program for at least 6 months will serve as the post-implementation group. These patients will be administered the same survey. The results from both groups will be analyzed to see how effective the medication adherence program is.

The purpose of this study is to test the safety and tolerability of using a new treatment called autologous T lymphocyte chimeric antigen receptor cells against the CSPG4 antigen (iC9.CAR-CSPG4 T cells) in patients with head and neck cancer that came back after receiving standard therapy for this cancer. The iC9.CAR-CSPG4 treatment is experimental and has not been approved by the Food and Drug Administration. How many (dose) of the iC9.CAR. CSPG4 T cells are safe to use in patients without causing too many side effects, and what is the maximum dose that could be tolerated will be investigated. The information collected from the study would help cancer patients in the future. There are two parts to this study. In part 1, blood will be collected to prepare the iC9.CAR-CSPG4 T cells. Disease fighting T cells will be isolated and modified to prepare the iC9.CAR-CSPG4 T cells. In part 2, the iC9.CAR-CSPG4 T cells are given by infusion after completion of lymphodepletion chemotherapy. The data from the dose escalation will be used to determine a recommended phase 2 dose (RP2D), which will be decided based on the maximum tolerated dose (MTD). Additionally, recommended phase 2 dose will be tested. Eligible subjects will receive lymphodepletion chemotherapy standard followed by infusion of iC9-CAR.CSPG4 T cells. After treatment completion or discontinuation, subjects will be followed since involving gene transfer experiments.

This study will assess the feasibility of incorporating biometric data via wearable health technology (WHT) into the radiation oncology (RO) clinic workflow for patients receiving concurrent radiation therapy and systemic therapy (CRT) for cancer. The investigators hypothesize that a practical workflow could be created within a busy community RO practice that will allow providers and patients to readily appreciate physiologic declines during concurrent CRT. Subjects will be asked to wear a device as part of this study that will collect their biometric data (heart rate, number of steps taken per day, etc) called a WHT device throughout their treatment and for 4 weeks afterward. Subjects will be asked to upload the data from their devices onto the computers in the clinic for the assessment.

This clinical trial evaluates the combination of olomorasib and pembrolizumab as a first-line treatment for patients with advanced or metastatic non-small cell lung cancer (NSCLC) that has a Kirsten Rat Sarcoma Virus (KRAS) G12C mutation and a programmed death-ligand (PD-L1) score between 1% and 49%. The main goal of the study is to determine how long patients live without their cancer worsening after starting treatment, also known as progression-free survival (PFS). Additional goals include evaluating how many patients experience tumor shrinkage or disappearance, how long responses to treatment last, overall survival, and the safety and side effects of the treatment combination. Furthermore, how well the treatment works in patients whose cancer has spread to the brain, outcomes in patients with a lower Eastern Cooperative Oncology Group performance status (ECOG), and whether certain tumor or blood-based biomarkers are associated with treatment response or side effects, if enough patient data is available for analysis.

Radiation therapy is an essential treatment for tumors in the chest area, including breast, lung, esophageal, mediastinal cancers, and spine metastases. Although technical advances have reduced treatment-related illness and death, radiation exposure to the heart can still cause substantial rates of radiation-induced heart disease (RIHD) among survivors. For example, about 21% of non-small cell lung cancer patients receiving a mean heart dose of 20 Gy or higher experience major adverse cardiac events (MACE) within 2 years. In breast cancer patients, the risk of MACE increases by about 7% for each additional Gy of mean heart dose. There is currently no established medication strategy to prevent or reduce RIHD. Preclinical and clinical studies show that statins and angiotensin-converting enzyme (ACE) inhibitors may help reduce radiation-induced heart disease (RIHD). Statins and ACE inhibitors are generally well tolerated, available as generic drugs, and commonly used to help prevent cardiovascular disease. They may protect the heart by reducing damage to blood vessel lining (endothelial damage), microvascular dysfunction, atherosclerosis, reduced blood flow (ischemia), and fibrosis (scarring). This study is a prospective, randomized, placebo-controlled phase II hybrid decentralized trial. Patients receiving standard radiation therapy and expected to receive an equivalent dose of at least 25 Gy (EQD2) to at least 10% of the heart will be randomly assigned to receive either: * placebo, or * Atorvastatin 20 mg plus Lisinopril 5 mg daily. The medications will be taken during radiation therapy and continued for 6 months after treatment. The study aims to determine whether the intervention can reduce radiation-related decreases in blood flow to the heart, measured using myocardial perfusion imaging, such as positron emission tomography (PET), which is commonly used to evaluate the risk of coronary heart disease.

This health services study will assess a multidisciplinary intervention program directed at fatigue mitigation among patients diagnosed with indolent lymphomas. Specifically, 30 subjects with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and 10 subjects with Follicular Lymphoma (FL), marginal zone lymphoma (MZL), lymphoplasmacytic lymphoma (LPL), Waldenström's Macroglobulinemia, or Cutaneous T Cell Lymphoma (CTCL) will be included.