Aggressive Malignancy

Researchers are investigating CGT9486 (bezuclastinib) in a Phase 2 open-label study for adults with Advanced Systemic Mastocytosis (AdvSM), including Aggressive Systemic Mastocytosis (ASM), Systemic Mastocytosis with an Associated Hematologic Neoplasm (SM-AHN), and Mast Cell Leukemia (MCL). This study aims to evaluate the drug's safety, efficacy, pharmacokinetics, and pharmacodynamics in these conditions. Participants receive bezuclastinib tablets taken orally in continuous 28-day cycles. The study has two parts conducted over 18 months each: Part I focuses on identifying active and tolerable doses, while Part II assesses treatment effectiveness by measuring the modified IWG Objective Response Rate (ORR) and confirms exposure-response relationships. During the study, participants will undergo evaluations including blood and bone marrow tests, imaging for spleen and liver size, and monitoring of mutation levels and serum tryptase. Researchers will track adverse events, duration and time to response, progression-free and overall survival. The total study duration includes these assessments over 18 months.

This research evaluates (Z)-endoxifen as a potential treatment for premenopausal women with estrogen receptor positive (ER+) and HER2-negative breast cancer. The study is open-label and includes two parts: a pharmacokinetic (PK) part to understand how the body processes the drug, and a treatment part to assess the drug's effect on tumor growth by measuring the biomarker Ki-67. The trial is sponsored by Atossa Therapeutics, Inc. and aims to determine if (Z)-endoxifen can slow or stop tumor growth in this patient group. Participants in the PK part receive daily (Z)-endoxifen capsules at doses of 20 mg, 40 mg, or 80 mg, with some also receiving a monthly injection of goserelin, which temporarily stops estrogen production by the ovaries. The treatment part uses a combination of (Z)-endoxifen at 40 mg daily plus monthly goserelin injections. After 4 weeks, tumor tissue is sampled via biopsy to measure Ki-67 levels. If Ki-67 is 10% or less, participants may continue treatment for up to 24 weeks; if greater than 10%, they proceed to surgery earlier. Participants attend regular visits for treatment and assessments, including blood tests and breast biopsies to monitor drug levels and tumor response. The main outcomes measured include (Z)-endoxifen blood concentrations and tumor Ki-67 reduction after 4 weeks, along with tumor response after 24 weeks. Study participation lasts up to 6 months, followed by surgery and a one-month follow-up to evaluate safety and treatment effects.

Researchers are evaluating the safety and appropriate dose of increasing levels of the radioactive drug 131I-TLX101, given by intravenous infusion, combined with the best standard care in adults newly diagnosed with glioblastoma, a type of brain cancer. This open-label, single-arm study is conducted across multiple centers and aims to understand how patients tolerate this treatment alongside standard therapies. Participants receive escalating doses of 131I-TLX101 through an intravenous infusion along with the standard chemoradiation therapy known as the Stupp regimen, beginning 3 to 6 weeks after surgical removal of the tumor. The study includes a dose-finding phase to establish the recommended dose, with safety monitored throughout. The radioactive drug is administered in ascending doses, and the study observes participants for up to 62 weeks. During the study, participants will undergo regular safety assessments including laboratory tests of liver and kidney function, monitoring for adverse events, and evaluations of treatment-related toxicities for up to 62 weeks. Researchers will track the incidence and severity of dose-limiting toxicities and treatment-emergent adverse events. Participants must comply with radiation safety guidelines and attend scheduled visits for monitoring. The total study duration from screening until the end is about 62 weeks.

Researchers are evaluating a combination treatment for men with prostate cancer that has spread to other parts of the body and continued to grow despite treatments that lower male hormones. This phase I trial compares the effects of a radioactive drug called lutetium Lu 177 (177^Lu)-PSMA-617 alone and combined with a vaccine therapy called Sipuleucel-T. The goal is to see if the combination can better stimulate the immune system and control the cancer. Participants are randomly assigned to one of two groups. One group receives 177^Lu-PSMA-617 intravenously every 6 weeks for up to 6 cycles, while the other group receives the same radioactive drug plus Sipuleucel-T starting at week 8, given every 2 weeks for up to 3 doses. Both groups undergo various imaging scans such as PET/CT, bone scans, MRI, and blood tests to monitor response and safety throughout the study. During the trial, patients have blood samples taken and may undergo leukapheresis (removal of certain blood cells for vaccine preparation). They are followed closely with scans and clinical visits during treatment and after completion. Follow-up visits occur at 30 days, then every 3 months for up to a year, and every 6 months until disease progression. Researchers measure immune response, safety, tumor response, progression-free survival, and overall survival over up to 3 years of observation.

Researchers are evaluating the safety and therapeutic response of a new drug called 177Lu-AB-3PRGD2 in patients with tumors that test positive for Integrin αVβ3. This drug is designed to target these specific tumors, which express this integrin highly, making it a promising option for diagnosis and treatment. The study is an early phase 1, open-label, non-controlled, and non-randomized trial focused on measuring the radiation absorbed dose and therapeutic effects in patients whose tumors show high uptake of the drug. Participants receive a single intravenous dose of 1.48 GBq (40 mCi) of 177Lu-AB-3PRGD2 within one week after a whole-body 68Ga-RGD PET/CT scan to confirm tumor suitability. After treatment, blood samples are collected at multiple time points to measure drug radioactivity. Patients undergo serial whole-body planar and SPECT/CT imaging at several intervals to monitor the radiation distribution and assess the treatment response. During the study, participants will be closely monitored with repeated imaging and blood tests at scheduled times up to 168 hours post-injection. Researchers will analyze the internal radiation dose absorbed by normal organs and tumors and collect data on any adverse events for up to two months. The primary outcome is the standardized uptake value of the drug in both tumors and normal tissues over a one-year period. The study involves adults aged 18 to 80 years with integrin-positive tumors that have not responded to standard treatments.

Researchers are evaluating 177Lu-RAD204, a radiolabeled antibody targeting PD-L1, in a Phase 0/1 study involving participants with advanced solid tumors that express PD-L1. The study aims to assess the safety, tolerability, biodistribution, radiation dosimetry, and preliminary anti-tumor effects of this treatment. The main goal is to find the maximum tolerated dose and recommended doses for future studies in participants with cancers such as NSCLC, SCLC, triple-negative breast cancer, melanoma, head and neck cancer, endometrial cancer, and others with specific genetic markers. The study includes a pre-screening period for PD-L1 testing if needed, followed by a screening period lasting up to four weeks. Participants undergo a Phase 0 Imaging Period where a low dose of 177Lu-RAD204 is given to assess imaging quality, safety, and dosimetry over two weeks. This may be followed by a Phase 1 Treatment Period with escalating doses of 177Lu-RAD204 administered in cycles lasting six weeks each. Participants may receive multiple treatment cycles based on clinical benefit and safety evaluations. Dose-limiting toxicity is monitored for six weeks after the first treatment dose, and dosing intervals may be adjusted as agreed by the study team. During the study, participants will have imaging scans, safety evaluations, and laboratory tests to track the distribution and effects of 177Lu-RAD204. Researchers will measure pharmacokinetics, radiation dosimetry, and tumor responses up to 30 weeks. Safety and tolerability are closely monitored throughout. Participants must meet specific health and tumor criteria to join and will be observed for any adverse reactions. The total duration of participation varies depending on treatment response and tolerability.

Researchers are evaluating 177Lu-BetaBart, a 177Lu-labeled anti-B7-H3 monoclonal antibody, in patients with various relapsed or refractory solid tumors that are locally advanced, inoperable, or metastatic. This Phase 1/2a study aims to understand the safety, tolerability, how the drug moves through and affects the body, and early signs of anti-tumor activity. Eligible participants include adults 18 and older with cancers such as castration-resistant prostate cancer, colorectal cancer, lung cancers, head and neck cancer, ovarian, cervical, endometrial, triple negative breast cancer, and esophageal squamous cell carcinoma who have shown disease progression after recent treatments. The study has two main parts: a Phase 1 dose escalation phase to find the maximum tolerated or recommended dose using a Bayesian design, and a Phase 2a dose expansion phase at that recommended dose to confirm safety and observe preliminary anti-tumor effects. Participants receive 177Lu-BetaBart through intravenous infusions every six weeks. Each phase includes a screening period, treatment and imaging period, and a safety and long-term follow-up period to closely monitor outcomes and side effects. During the study, participants undergo assessments including imaging for disease evaluation, laboratory tests for organ function and drug effects, and monitoring of side effects for up to 30 weeks. Key outcomes include determining the suitable dose for future studies, tracking adverse events, and measuring anti-tumor activity through objective response rates and biochemical responses in prostate cancer. Pharmacokinetics, radiation dosimetry, and biokinetics of the drug are also measured at specified time points. Safety and tolerability are evaluated continuously, with follow-up to monitor long-term effects and overall health.

Researchers are evaluating how well 177Lu-DOTATATE works to treat patients with stage IV or recurrent breast cancer that shows evidence of a protein called SSTR2. This phase II study explores whether this targeted therapy can shrink or destroy tumors and circulating cancer stem cells in the blood. 177Lu-DOTATATE combines a radioactive agent with DOTATATE, which attaches to tumor cells with SSTR2 to deliver targeted treatment. Participants receive 177Lu-DOTATATE intravenously over 30 to 40 minutes during weeks 1, 8, 16, and 24 if their disease does not progress and they do not experience unacceptable side effects. Before treatment, patients undergo imaging with gallium 68-DOTATATE PET/CT scans and biopsies as needed. Throughout the study, patients have CT or MRI scans and blood samples collected to monitor disease and treatment effects. After completing the treatment phase, participants are followed every 3 months for up to 5 years. The research team measures tumor response, disease control, duration of treatment effect, progression-free survival, and treatment safety. Blood tests, imaging, and biopsies help track how well the therapy works and any side effects, supporting long-term monitoring of patient health.

Researchers are evaluating a new dual targeting PET radiotracer called 18F-FAPI-Biotin in patients with various types of cancer. This tracer aims to improve tumor detection by targeting both fibroblast activation protein, which is highly expressed in many cancer stromas, and biotin, which is overexpressed in tumor cells but underexpressed in normal cells. The study focuses on assessing the safety, how the tracer distributes in the body, and the radiation dosimetry compared to existing tracers like 18F-FAPI and 18F-FDG. Participants receive an intravenous dose of 148-296 MBq of 18F-FAPI-Biotin. PET imaging is conducted dynamically at multiple time points: 3 minutes, 15 minutes, 30 minutes, 60 minutes, and 120 minutes after injection. This allows researchers to observe the tracer's pharmacokinetics and dosimetry across different organs and tumors. The study is classified as an early phase 1 trial. During the study, patients undergo PET/CT scans at the specified time points following tracer injection. Researchers monitor the dosimetry of normal organs and tumors from immediately after injection up to 120 minutes later. Safety assessments include tracking adverse events for up to one week using standard criteria. The total participation duration includes imaging sessions and safety monitoring to evaluate the tracer's distribution and potential side effects.

Researchers are evaluating a new PET imaging tracer called [18F]FAPI-74 to detect cancer by targeting the fibroblast-activation protein (FAP) found in cancer-associated fibroblasts. This study aims to compare [18F]FAPI-74 PET scans to the standard [18F]-FDG PET scans and other imaging methods like CT or MRI across several cancers including pancreatic ductal adenocarcinoma, cholangiocarcinoma, hepatocellular carcinoma, gastric, bladder, ovarian cancers, pheochromocytoma/paraganglioma, small cell lung cancer, neuroendocrine cancer, mesothelioma, and sarcoma. The study is a phase 2 interventional trial conducted by the National Cancer Institute (NCI). Participants will receive an intravenous dose of [18F]FAPI-74 before undergoing PET/CT imaging about one hour later. They will also have a baseline FDG PET scan within one week. If tumors are detected by [18F]FAPI-74, additional scans using this tracer and FDG may be repeated during routine treatment and if cancer progresses within two years. Those with negative baseline [18F]FAPI-74 scans will not have repeated scans but remain in follow-up. The study involves a single arm where participants undergo both types of PET imaging. During the study, participants will have scans at baseline and potentially at subsequent treatment or progression points. Safety monitoring includes observation for reactions to the tracer up to three days after injection. Researchers will measure the mean number of lesions, standardized uptake values at baseline, post-treatment, and recurrence. Follow-up calls will continue for two years to assess progression-free survival and overall survival. The total participation duration includes imaging visits and two years of follow-up monitoring.