Uterine Cancer

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 studying men with metastatic castration-resistant prostate cancer (mCRPC) to understand how different PET/CT scans can predict outcomes during radioligand therapy with 177Lu-PSMA-617. This is an exploratory, prospective study conducted at a single center, focusing on imaging tumor heterogeneity to help assess therapy effects and patient response. The study is designed specifically for Veterans undergoing this treatment. Participants will receive several types of PET/CT scans at different times: before starting LuPSMA radioligand therapy (RLT), and then after the 2nd, 4th, and 6th treatment cycles. These scans include 18F-Fluciclovine PET/CT (Axumin), 18F-DCFPyL PET/CT, and 18F-FDG PET/CT. The 18F-Fluciclovine scans will be performed within seven days of the PSMA PET scans to compare imaging results at each time point. During the study, detailed imaging measures such as lesion uptake and tumor volume will be collected and analyzed over time. Patients will be followed at the institution to correlate these imaging results with clinical outcomes. The main outcome measured is the impact of 18F-Fluciclovine PET/CT on predicting outcomes of the 177Lu-PSMA-617 therapy from enrollment through 34 weeks of treatment.

Researchers are evaluating the diagnostic value of a new protein-specific probe called 18F-T2 in PET/CT imaging for people with solid tumors that are likely to express high levels of CAIX protein. The study will also assess how safe and tolerable the 18F-T2 injection is, as well as measure its radiation dosage. This research is important to better understand how well 18F-T2 can detect these tumors compared to standard imaging techniques. Participants with tumors suspected to express high levels of CAIX will receive an intravenous injection of 18F-T2. About an hour after the injection, PET/CT imaging will be performed to capture detailed images of the tumors. Within one week, participants will also undergo a whole-body PET/CT scan using 18F-FDG, a commonly used imaging agent, to allow comparison between the two imaging methods. During the study, participants will be monitored for any adverse events within 24 hours after the 18F-T2 injection to evaluate safety and tolerability. Researchers will measure the diagnostic sensitivity and specificity of 18F-T2 PET/CT for detecting CAIX-positive tumors. They will also assess uptake values in tumors on both 18F-T2 and 18F-FDG scans, analyze the correlation between 18F-T2 uptake and CAIX expression in tissue samples, and evaluate radiation dosimetry. The study will continue until one month after completion for outcome assessments.

Researchers are evaluating the use of 3D-printed custom applicators for intracavitary high-dose-rate (HDR) brachytherapy in patients with gynaecological cancers, including endometrial, vaginal, vulva, and recurrent gynaecological cancers. This Phase IIa non-randomised pilot trial aims to assess the feasibility of treating patients using these patient-specific devices, which could offer a more precise and efficient alternative to traditional cylinder-type applicators or custom wax moulds. The study is sponsored by Royal North Shore Hospital and addresses current challenges in applicator design and construction. Participants will receive treatment using 3D-printed custom applicators designed to match optimal planning specifications for HDR brachytherapy. This innovative approach may reduce the time and labor involved in applicator preparation compared to standard wax moulds, while providing a robust and tailored device for therapy. The study focuses on intracavitary brachytherapy procedures for eligible female patients with certain stages of gynaecological cancer. During the study, patients will be closely monitored for treatment success, radiation therapy toxicities, and quality of treatment plans. Researchers will also evaluate the feasibility of MR-only and CT-only planning procedures, optimize applicator design, and assess resource use and costs. Patient experience and acceptability will be measured via questionnaires over a five-year follow-up. Safety and effectiveness outcomes will be carefully tracked to understand the potential benefits and challenges of this new technology.

Researchers are investigating the use of 3D ultrasound imaging during brachytherapy treatment for gynecological cancers, including primary or recurrent vaginal, endometrial, and cervical cancers. This study aims to improve needle placement accuracy in interstitial or intra-cavitary brachytherapy, which is important for delivering adequate radiation doses to tumors while protecting healthy pelvic organs. Currently, there is no standard real-time image guidance for needle insertion in these procedures, which this research seeks to address. The study involves patients receiving gynecological brachytherapy using a device-based approach, where needles and applicators are inserted under general anesthesia with guidance from clinical exams and pre-procedure MRI. An investigational 3D ultrasound device will be used during the procedure to provide real-time volumetric imaging of needle pathways, improving upon the limitations of standard 2D ultrasound. After the procedure, CT scans are performed for radiation planning. Participants will undergo imaging assessments including MRI before treatment and CT after treatment, with the main focus on measuring the accuracy of needle placement over a 16-month period. The study team will evaluate how effectively the 3D ultrasound helps avoid needle insertion into pelvic organs and optimizes tumor dose coverage. Patient safety and treatment monitoring will be conducted alongside these measurements within the study timeline.

Researchers are evaluating the use of a new imaging method called [18F]fluoroestradiol (FES) PET/CT to study estrogen receptor activity in women with recurrent, metastatic, or non-operated uterine cancer. This phase II study aims to understand how estrogen receptors are present in the cancer, which could help guide future research and treatments. The study involves women who are at least 18 years old and receiving care at the University of Pennsylvania. Participants will undergo up to two PET/CT scans using the investigational FES tracer. The first scan is required and happens before starting a new therapy. Some patients may have a second optional scan if their disease progresses, to compare changes in estrogen receptor activity. The choice of therapy will remain with the treating doctor and will not be influenced by the scan results. Optional biopsies and blood samples may also be collected to study tumor cells and hormone levels. During the study, participants will have scans from the skull base to mid-thigh about 60 minutes after receiving the FES injection. Researchers will review standard imaging and clinical exams to evaluate cancer sites. Optional blood draws will analyze circulating tumor cells and hormone levels. The main outcome measured is the rate of FES positivity in estrogen receptor-positive uterine cancer over one year. Safety, progression, and changes in imaging and pathology will also be monitored. Participation may last up to several years as outcomes and progression are followed.

Researchers are evaluating MDNA11, a long-acting "beta-only" recombinant interleukin-2 designed to activate immune cells that kill cancer while minimizing activation of immunosuppressive cells. This Phase 1/2 study aims to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and early anti-tumor activity of MDNA11 alone or combined with the checkpoint inhibitor pembrolizumab in patients with advanced solid tumors. The study is conducted at multiple sites with regulatory and ethical approvals and includes about 115 patients. The trial has several parts: dose escalation and expansion for MDNA11 monotherapy and for its combination with pembrolizumab. MDNA11 is given intravenously every two weeks with doses adjusted to find the recommended dose for expansion. Tumor assessments using CT or MRI scans happen every 8 weeks to monitor response until disease progression or other study-end criteria occur. Treatment may continue beyond progression under certain conditions. Participants undergo evaluations including tumor imaging, laboratory tests, and safety monitoring over up to 24 months. Researchers measure recommended dose levels, treatment-related adverse events, pharmacokinetics, immune response, and anti-tumor activity such as response rates and progression-free survival. Patients can withdraw anytime, and safety follow-up continues to understand MDNA11's effects alone and with pembrolizumab.

Researchers are evaluating the safety and effectiveness of CD70-targeted CAR-T cells in treating patients with CD70-positive advanced or metastatic gynecologic cancers. This Phase 1 study focuses on patients who have not responded to standard treatments and aims to find the best doses and infusion methods for these CAR-T cell therapies. The study has two groups based on how the CAR-T cells are given: one group receives the treatment through intravenous infusion, and the other through intraperitoneal injection. Each group undergoes two phases: a dose discovery phase that uses a dose-escalating design to find recommended doses, followed by a dose expansion phase to further evaluate safety and effectiveness at those doses. Participants receive doses ranging from 1 to 10 million cells per kilogram. Participants will be closely monitored for adverse events and treatment effects over time. Researchers will assess safety outcomes within the first 28 days after infusion and effectiveness outcomes such as disease control and response rates over three months, with longer-term follow-up up to two years. Various lab tests, imaging scans, and clinical evaluations will be done to track how the CAR-T cells behave and impact the cancer. The total study duration and detailed monitoring are designed to ensure participant safety and collect data on how well the CAR-T cells work.

Researchers are investigating the effects of BNT323 (also known as DB-1303) compared with chemotherapy in women with recurrent endometrial cancer that expresses the HER2 protein. The study is divided into two groups based on HER2 levels in tumor samples. The first group includes participants with lower HER2 expression who have previously received immune checkpoint inhibitors, while the second group includes participants with higher HER2 expression receiving BNT323 alone. The study also monitors safety, immune response, and quality of life. Participants in the first group will be randomly assigned to receive either BNT323 or chemotherapy drugs such as doxorubicin, paclitaxel, or docetaxel, depending on what is suitable. The second group will receive BNT323 alone. Treatments are given until the disease progresses, unacceptable side effects occur, or participants choose to stop. The study includes screening, treatment, safety follow-up, efficacy follow-up, and a long-term survival follow-up lasting up to 53 months. During the study, participants will undergo regular assessments to measure how well the treatments control cancer progression or shrink tumors. Safety is closely monitored by tracking side effects and how the body processes BNT323. Researchers will also evaluate overall survival and quality of life. The expected treatment period is about six months, with long-term follow-up to observe survival outcomes over several years.