Advanced Malignancy

Researchers are evaluating the efficacy and safety of Thymalfasin combined with targeted immunotherapy drugs Regorafenib and Tislelizumab compared to Regorafenib and Tislelizumab alone in patients with advanced mismatch repair-proficient (pMMR) or microsatellite stable (MSS) colorectal cancer who have not responded to standard treatments. This Phase II randomized controlled study aims to compare progression-free survival between these two treatment approaches. The study will enroll 52 subjects across multiple centers with specific statistical assumptions guiding enrollment and analysis. Participants will be randomly assigned to one of two groups: a triple therapy group receiving Thymalfasin subcutaneously twice weekly along with oral Regorafenib and intravenous Tislelizumab, or a double therapy group receiving only Regorafenib and Tislelizumab. Regorafenib will start at 80 mg orally daily for two weeks followed by a one-week break, with an increase to 120 mg daily if tolerated. Tislelizumab is given by intravenous infusion once every 21 days. Treatment continues until disease progression according to iRECIST criteria or unacceptable side effects occur. During the study, participants will be monitored for disease progression and adverse events with regular assessments including imaging to measure tumor response. The primary outcome is progression-free survival at 48 weeks. Secondary outcomes include 18-week progression-free survival rate, objective response rate, disease control rate, and overall survival up to three years. Safety and tolerability will also be assessed throughout the trial. The total study duration includes enrollment over 9 months and follow-up for up to 15 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.

This trial investigates treatment options for patients with microsatellite stable (MSS) or proficient mismatch repair (pMMR) metastatic colorectal cancer who do not have active liver metastases. It is a phase II, prospective, randomized, open-label study conducted across multiple centers. The study aims to evaluate the effectiveness of Fruquintinib combined with Tislelizumab compared to a control treatment in this specific patient group. Participants will be randomly assigned to one of two groups. One group will receive Fruquintinib orally once daily for 21 days in a 28-day cycle along with Tislelizumab given intravenously every 42 days. The other group will receive Trifluridine/tipiracil orally twice daily on specific days of a 28-day cycle plus Bevacizumab intravenously every 14 days. Treatment will continue until disease progression, unacceptable side effects, patient choice, or a maximum of 15 months. During the study, patients will undergo regular assessments including imaging scans to monitor disease status, evaluations of side effects, and quality of life measures. Follow-up will continue for up to 18 months after the last patient begins treatment or until death, withdrawal, or loss to follow-up. Researchers will primarily measure the efficacy of the Fruquintinib and Tislelizumab combination, along with overall survival, response rates, safety, and quality of life.

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-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 the safety and effects of combining a targeted radionuclide therapy called 177Lu-PSMA-617 with liver-directed treatments in men who have metastatic castration-resistant prostate cancer (mCRPC) with liver metastases. This phase 1b open-label study focuses on patients whose cancer has progressed despite prior androgen pathway inhibitor treatments. The study aims to understand how well this combined approach controls disease and its safety profile using standard response criteria. Participants receive up to six cycles of 177Lu-PSMA-617 intravenously every 6 weeks. Those with PSMA-negative liver lesions receive a single session of liver-directed therapy such as transarterial chemoembolization (TACE) or ablation before starting the radionuclide treatment. If liver disease remains stable or progresses after two cycles, additional liver-directed therapy may be given. Treatment continues until disease progression, unacceptable side effects, or study completion. During the study, participants undergo imaging tests like PET/CT scans, tumor biopsies, and complete questionnaires to assess responses. Researchers monitor safety through adverse event reports and measure outcomes such as objective response rates, progression-free survival, overall survival, and prostate-specific antigen (PSA) declines. Follow-up visits occur every 3 months for up to 5 years after the last treatment to track long-term effects.

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.