Nashville

Researchers are evaluating an imaging test called zirconium Zr89 panitumumab combined with PETCT scans to detect the spread of head and neck squamous cell carcinoma to other parts of the body. This phase I trial aims to assess how well 89Zr panitumumab identifies uncertain metastatic lesions compared to standard imaging methods like MRI, CT, and 18F-FDG PETCT. The study focuses on the sensitivity and specificity of this investigational imaging agent in diagnosing metastatic disease. Participants will receive intravenous infusions of panitumumab and 89Zr panitumumab, followed by a PETCT scan within 1 to 5 days after the infusion. They will also undergo standard care evaluations and treatments for their suspected metastatic lesions. The study compares 89Zr panitumumab PETCT results to those from usual imaging techniques to determine its diagnostic value. During the study, participants will have blood tests to check hemoglobin, white blood cell count, platelet count, and kidney function. Researchers will monitor the imaging results to measure sensitivity and specificity over up to seven years. The study also tracks how often invasive procedures like biopsies are chosen versus observation. Participants will be followed and evaluated for safety and diagnostic accuracy throughout the study period.

Researchers are evaluating the combination of CGT9486 and sunitinib compared to sunitinib alone in patients with locally advanced, unresectable, or metastatic Gastrointestinal Stromal Tumors GIST. This Phase 3, open-label international trial involves multiple parts, including dose confirmation, drug interaction assessments, and efficacy comparisons. The study also includes substudies focusing on drug-drug interaction potential and first-line treatment in patients with specific genetic mutations KIT exon 9. Approximately 482 patients will participate across these parts.

Researchers are evaluating the effects of scavenging isolevuglandins IsoLGs with 2-HOBA on blood pressure and immune activation in patients with systemic lupus erythematosus SLE, an autoimmune disease linked to high rates of hypertension and cardiovascular risks. This phase II randomized, placebo-controlled, double-blind, cross-over trial aims to understand the role of IsoLGs in SLE-related hypertension and immune responses. Participants will receive either placebo or 500mg of 2-HOBA acetate three times a day for 8 weeks, followed by a 4-week washout period, then switch to the other treatment for another 8 weeks. The study includes two treatment sequences placebo first then 2-HOBA, or 2-HOBA first then placebo. This design allows comparison of blood pressure and immune activity changes between treatments. During the study, 42 women with stable SLE will undergo evaluations including 24-hour blood pressure monitoring and measurement of NETosis at baseline and at weeks 8, 12, and 20. Researchers will monitor immune activation and blood pressure changes to assess the impact of 2-HOBA compared to placebo. The total participation includes treatment periods and washout spanning 20 weeks.

Researchers are evaluating the effects of 2-Hydroxybenzylamine 2-HOBA on people with heterozygous Familial Hypercholesterolemia FH. The study aims to test whether 2-HOBA can reduce harmful modification of HDL and LDL cholesterol and improve HDL function. This phase 2 trial is focused on prevention and involves a randomized, placebo-controlled design with quadruple masking to ensure objective results. Participants receive either 750 mg of 2-HOBA given as three 250 mg capsules three times daily or a placebo for six weeks. The study compares these two groups in parallel to assess the impact of 2-HOBA on cholesterol modification and function. The treatment period lasts six weeks, during which participants take the assigned capsules orally. Throughout the study, participants undergo assessments to measure HDL cholesterol efflux capacity and the extent of HDL modification by specific agents like Isolevuglandin and malondialdehyde. These measurements are taken from baseline through week 6. Researchers monitor participants health and safety, with the total involvement lasting at least the six-week treatment period. The trial is sponsored by Vanderbilt University Medical Center and continues through the end of 2027.

Researchers are evaluating the safety and effects of a gene therapy called 4D-150 in adults aged 50 years and older with neovascular wet age-related macular degeneration AMD who are currently receiving anti-VEGF treatments and have shown a positive response. This Phase 12 trial includes a dose-escalation stage, a randomized controlled expansion phase, and additional cohorts to optimize steroid use and extend the population studied. The study also includes substudies to assess dosing safety in the opposite eye and to examine vector shedding. Participants receive a single injection of 4D-150 into the eye on Day 1 at assigned dose levels. Some participants receive aflibercept injections as an active comparator. Following the injection, participants are monitored monthly for 24 months to track safety and treatment effects. Those who receive 4D-150 enter a long-term follow-up period lasting up to five years to evaluate extended safety and the duration of the gene therapys activity. The substudies include one-time dosing in the contralateral eye and assessments of vector shedding, with safety monitored for one year and continued follow-up through five years. Throughout the study, participants undergo regular eye function and structure tests, including visual acuity and retinal thickness measurements using imaging technologies. Researchers track adverse events and the need for additional aflibercept injections, as well as changes in vision and retinal health. Participants must comply with study procedures and agree to use barrier methods during and after treatment to prevent fluid transmission. The study ensures comprehensive safety monitoring, with evaluations continuing for up to five years after treatment administration.

Alpha-synucleinopathies are age-related neurodegenerative disorders characterized by the build-up of alpha-synuclein in nerve cells, leading to conditions like Parkinsons disease, Multiple System Atrophy, and Dementia with Lewy Bodies. Pure Autonomic Failure is a related condition affecting the peripheral autonomic nervous system and may signal risk for developing central nervous system synucleinopathies. Researchers aim to identify biomarkers, especially changes in dopamine production in key brain areas, to predict progression from peripheral to central disease. Participants receive a radiolabeled drug called 18FF-DOPA, which is used in PET scans to study dopamine activity in the brain. Before the PET scan, patients take oral doses of carbidopa and entacapone to enhance imaging quality by reducing peripheral metabolism of 18FF-DOPA. The PET scan involves a slow injection of 18FF-DOPA followed by about 95 minutes of serial brain imaging to observe dopamine-related changes. During the study, participants undergo clinical exams to confirm diagnosis and receive the PET imaging procedure. Researchers measure differences in 18FF-DOPA uptake across patient groups 95 minutes after imaging starts to assess dopamine function. The study includes patients with autonomic failure, possible synucleinopathies, and healthy adults aged 18 and older. The study is designed to monitor safety and gather detailed imaging data over the scan period.

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 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 studying metastatic castration-resistant prostate cancer mCRPC to find new treatment options. This trial evaluates if the study medicine ifinatamab deruxtecan I-DXd or MK-2400 helps people live longer overall and experience slower cancer growth or spread compared to chemotherapy. The study is a Phase 3 trial comparing I-DXd with standard chemotherapy for mCRPC patients. Participants are randomly assigned to receive either I-DXd at 12 mgkg every 3 weeks through intravenous infusion or docetaxel chemotherapy at 75 mgm2 every 3 weeks combined with daily prednisone pills. Treatment continues until the disease progresses, unacceptable side effects occur, or treatment is stopped for other reasons. Premedication is given before each dose of I-DXd to help prevent nausea and vomiting. During the study, participants will have regular visits for treatment and monitoring. Researchers will assess overall survival and radiographic progression-free survival for up to about 36 months. Additional measures include response rates, time to pain progression, PSA progression, and adverse events. The study tracks safety, treatment effects, and quality of life over a long follow-up period to better understand the potential benefits and risks of I-DXd compared to chemotherapy.

Researchers are evaluating MK-1045, an immunotherapy, in people with two types of non-Hodgkin lymphoma NHL follicular lymphoma FL, which grows slowly, and diffuse large B-cell lymphoma DLBCL, which grows more quickly. NHL is a cancer of the lymphatic system causing swollen lymph nodes. This study aims to assess the safety and tolerability of MK-1045 and to see if it can shrink or eliminate these lymphomas. Participants are randomly assigned to one of four groups receiving different doses or methods of MK-1045 administration. Dosages A, B, and D are given by intravenous IV infusion, while Dosage C is given by subcutaneous SC injection. Treatment lasts for up to approximately one year or until participants stop treatment for any reason. During the study, participants will be monitored for adverse events and treatment side effects, with measurements including tumor response using specific criteria. Blood levels of MK-1045 will also be tracked. The study involves regular visits for infusions and assessments. Participant safety and treatment effects will be followed for up to about 49 months in total.