Cervical Cancer

Researchers are studying 177Lu-BetaBart, a 177Lu-labeled anti-B7-H3 monoclonal antibody, to understand its safety, how it moves and distributes in the body, and its preliminary effectiveness against certain solid tumors. This study focuses on patients aged 18 and older with relapsed or refractory locally advanced, inoperable, or metastatic solid tumors including castration-resistant prostate cancer, colorectal cancer, various lung cancers, head and neck squamous cell carcinoma, ovarian, cervical, endometrial, triple negative breast, and esophageal squamous cell carcinoma. The trial has two phases to evaluate safety and early anti-tumor activity, using advanced study designs to identify appropriate dosing and response rates. The study involves two main phases: Phase 1 is a dose escalation phase where participants receive intravenous infusions of 177Lu-BetaBart every 6 weeks to determine the maximum tolerated dose and recommended dose for Phase 2. Phase 2a is a dose expansion phase conducted at the recommended dose to further assess safety and early anti-tumor effects. Each phase includes a screening period, treatment and imaging period, and a safety and long-term follow-up period. Participants will undergo various assessments including imaging scans and laboratory tests to monitor disease progression, treatment safety, and biological responses over periods up to 6 weeks for Phase 1 and up to 30 weeks for Phase 2a. Researchers will track adverse events, dose recommendations, and measure tumor activity using biochemical markers and imaging. Long-term safety and treatment effects will be followed after the treatment periods to gather comprehensive clinical data.

The imaging analysis will consist in obtaining quantitative measurements of lesion uptake on the pre- and post-LuPSMA RLT (lesion and whole-body SUVmax, SUVmean and tumor volume) at each time point on all PET/CT scans. PET metrics at the lesion- and whole-body level will be compared among different PET radiopharmaceuticals at the same time point, and changes over time will be assessed. All patients will be followed-up at our institution and clinical outcome will be correlated to the imaging analysis assessment.

Researchers are evaluating the diagnostic usefulness of a new protein-specific imaging probe called 18F-T2 in PET/CT scans for participants with solid tumors that may express high levels of the CAIX protein. This trial also aims to assess the safety, tolerability, and radiation exposure from using 18F-T2. The study includes various types of cancers such as renal cell, urothelial, colorectal, cervical, ovarian, head and neck, liver, bile duct, lung, breast, pancreatic, endometrial cancers, and Von Hippel Lindau Disease. Participants will receive an intravenous injection of 18F-T2 at a dose of 0.05-0.10 mCi/kg. About 60 minutes after the injection, they will undergo combined CT and PET imaging sessions to evaluate tumor detection using this new probe. The study focuses on measuring the diagnostic sensitivity and specificity of 18F-T2 PET/CT and monitoring adverse events shortly after injection. During the study, participants will be closely monitored for side effects within 24 hours of receiving the injection. Researchers will collect imaging data from the PET/CT scans and assess diagnostic accuracy up to one month after study completion. Participants must provide informed consent and comply with all study requirements throughout their involvement. The total duration and follow-up involve safety and diagnostic performance evaluation after the imaging procedure.

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, and vulva cancers, as well as recurrent gynaecological cancers. This Phase IIa non-randomised interventional pilot trial aims to determine if these 3D-printed devices can be successfully used for treatment, offering a more efficient and precise alternative to traditional cylinder-type applicators or custom wax moulds. The study focuses on improving the design, manufacturing, and delivery of brachytherapy applicators to better conform to the treatment area while potentially reducing complexity and production time. Participants will receive treatment using 3D-printed custom applicators specifically designed for their anatomy. These devices are created through a streamlined workflow that allows for patient-specific customization matching the optimal design specifications dictated by the treatment planning system. This approach is expected to result in a more robust and reliable applicator for delivering radiation therapy in comparison to current methods, which can be time consuming and sometimes fail to meet design requirements. The study does not include a comparator group but focuses on the feasibility of this novel treatment process. During the study, patients indicated for intracavitary brachytherapy will be closely monitored to assess the successful delivery of treatment with these 3D-printed applicators over a period of 5 years. Researchers will evaluate treatment outcomes, safety, and the ability to conform radiation doses effectively to the target areas. Patient assessments will include clinical evaluations and treatment planning reviews to ensure the applicators meet the required specifications. The study also involves careful follow-up to monitor for any complications or treatment failures related to the applicators used.

Brachytherapy is an important treatment for gynecological cancers, helping deliver radiation directly to tumors while minimizing exposure to healthy tissue. This research focuses on advanced or recurrent gynecological cancers where interstitial or intra-cavitary brachytherapy is required because standard intrauterine brachytherapy may not be optimal. The study aims to improve needle placement during brachytherapy by using 3D ultrasound imaging to guide needle insertion in real time, potentially avoiding injury to pelvic organs and improving radiation coverage of the tumor. Participants will undergo gynecological brachytherapy, which involves placing radioactive sources near or inside the tumor using a defined template-and-needle system. The study will compare standard needle placement techniques with the use of 3D ultrasound imaging during the procedure. This device-based approach seeks to enhance the accuracy and safety of needle insertion during brachytherapy. Throughout the study, researchers will monitor needle localization accuracy over 16 months. Participants will receive assessments to evaluate the positioning of needles during treatment and ensure optimal radiation delivery. This study involves female patients aged 18 or older with specific gynecological cancers who are offered interstitial or ring and tandem brachytherapy treatment. Safety and treatment effectiveness will be carefully observed during and after therapy.

Researchers are evaluating the safety and tolerability of increasing doses of [177Lu]Lu-AKIR001 in adults with irresectable or metastatic solid tumors that express CD44v6, for which no reasonable systemic treatment options exist. This early phase 1 trial aims to understand the toxicity profile of the study drug by monitoring dose limiting toxicities and severe adverse events. The study focuses on patients with certain advanced cancers, including thyroid gland anaplastic carcinoma, poorly differentiated thyroid carcinoma, head and neck cancer, cervical carcinoma, vulvar cancer stage IV, and stage IV non-small cell lung cancer. Participants will receive an infusion of [177Lu]Lu-AKIR001, with doses increasing across up to five groups to evaluate safety at different protein mass doses and activity levels. After the initial infusion, there will be a safety follow-up period of at least six weeks, which can be extended up to twelve weeks. Depending on clinical benefit and acceptable toxicity, participants may receive up to a total of four infusions during the trial. During the study, participants will undergo assessments to monitor safety and treatment effects, including evaluations of dose limiting toxicities from the first dose through at least six weeks post-dose. Organ and bone marrow functions will be tested before infusion, and participants' overall health status will be closely observed. The main outcome measured is the rate of dose limiting toxicities during the minimum six-week post-infusion period. The study ensures continuous monitoring to assess the drug's safety and tolerability in this patient population.

Researchers are evaluating MDNA11, a long-acting "beta-only" recombinant interleukin-2 designed to activate immune cells that attack cancer while minimizing stimulation of cells that suppress immunity. This Phase 1/2 open-label study aims to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and early anti-tumor activity of MDNA11 alone or combined with pembrolizumab in patients with advanced or metastatic solid tumors. The study includes dose-escalation and dose-expansion parts for both monotherapy and combination therapy with pembrolizumab. MDNA11 is given intravenously every two weeks with doses ranging from 0.003 to 0.6 mg/kg for monotherapy, while dose ranges for combination therapy are also evaluated. Treatment continues until progression, withdrawal, or loss to follow-up, with tumor assessments by CT or MRI every 8 weeks. Participants will undergo regular imaging scans every 8 weeks to monitor tumor response and safety assessments throughout the 24-month study. Researchers will track recommended doses for expansion, treatment-related adverse events, and overall safety. The study involves up to 115 patients across multiple sites and includes long-term monitoring for up to 24 months.

Researchers are evaluating the safety and effectiveness of CD70-targeted CAR-T cells in treating patients with CD70-positive advanced or metastatic gynecologic cancers, including ovarian and cervical cancers. This Phase I, single-center, open-label study aims to find the recommended doses and infusion methods for these CAR-T cells. The study includes participants who have not responded to or cannot tolerate standard treatments and have measurable tumors. The study has two treatment groups: one receives CAR-T cells through intravenous infusion, and the other receives them via intraperitoneal injection. Each group undergoes two phases: a dose discovery phase using a dose-escalation design to find the suitable doses, followed by a dose expansion phase to confirm safety and effectiveness of the selected doses. Lymphodepletion with Fludarabine and Cyclophosphamide is given before CAR-T cell administration. Participants will be closely monitored for safety and adverse events for 28 days after infusion. Researchers will assess the maximum tolerated dose of CAR-T cells and observe treatment effects. The study involves various evaluations including physical exams, laboratory tests, and imaging to measure tumor response and overall health. Participants must agree to contraception use and provide informed consent to join the trial.

Researchers are evaluating the safety and effectiveness of CD70-targeted CAR-T cell therapy in treating advanced or metastatic solid tumors that express the CD70 protein. This phase 1, single-center, open-label study aims to find the best doses and infusion methods for these CAR-T cells in patients whose tumors have not responded to other treatments. The study focuses on patients with CD70-positive cancers such as renal cell carcinoma, ovarian cancer, cervix cancer, and other advanced or metastatic cancers. The trial includes two groups receiving the CAR-T cell therapy by different methods: intravenous infusion and intraperitoneal injection. Each group undergoes two phases: a dose discovery phase and a dose expansion phase. In the dose discovery phase, four dose levels will be tested using a 3+3 design, enrolling about 12 patients per group. In the dose expansion phase, one or two dose levels from the discovery phase will be evaluated further for safety and effectiveness, with about six patients per dose level. All patients receive lymphodepletion treatment with Fludarabine and Cyclophosphamide before the CAR-T cell therapy. Participants will be closely monitored for safety and side effects for 28 days after receiving the CAR-T cells, including tracking adverse events and determining the maximum tolerated dose. The study will assess measurable tumor lesions to evaluate treatment response. Patients must meet specific health criteria and agree to follow study requirements, including contraceptive use and consent. The overall participation includes dose escalation, dose expansion, safety assessments, and ongoing monitoring to understand treatment tolerability and potential benefits.

Researchers are evaluating the safety and tolerability of CD70-targeted CAR-T cell therapy in patients with CD70-positive advanced or metastatic solid tumors, including renal cell carcinoma, ovarian cancer, and cervix cancer. This phase I clinical trial aims to determine the maximum tolerated dose and the recommended dose for phase II treatment. The study addresses patients who have not responded to or cannot tolerate standard treatments and have measurable tumors with positive CD70 expression confirmed by pathology. The trial includes two treatment groups receiving CD70 CAR-T cells either through intravenous infusion or intraperitoneal injection. Each group follows a dose-escalation 3+3 design with three dose levels planned. Before receiving the CAR-T cell infusion, participants are treated with Fludarabine and Cyclophosphamide. Approximately nine subjects will be recruited in each group. Participants will undergo evaluations of safety and adverse events for 28 days after CAR-T cell infusion to assess tolerability and identify the maximum tolerated dose. Eligibility requires adequate organ function, measurable disease, and an expected survival time of over 12 weeks. Continuous monitoring includes physical exams, laboratory tests, and imaging to observe treatment response and safety throughout the study.