Hormone Therapy

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 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 a 5-strain probiotic formulation called WBF-038 in women with early-stage hormone receptor-positive breast cancer who are starting treatment with aromatase inhibitors. Aromatase inhibitors reduce estrogen production to help stop cancer cell growth but can negatively affect bone health, weight, and blood sugar. This phase II trial aims to see if WBF-038 can prevent bone loss and improve metabolic health during this treatment. Participants take WBF-038 orally once daily for one year, starting three months after beginning aromatase inhibitor therapy, unless disease progression or unacceptable side effects occur. The study includes blood sample collections and bone mineral density tests at screening and throughout the trial. After the treatment year, participants are followed for an additional 90 days. During the study, researchers measure changes in bone turnover markers like C-terminal telopeptide of type 1 collagen (CTx), lumbar spine and hip bone mineral density, blood sugar levels, weight, waist size, and musculoskeletal symptoms. Safety is closely monitored through adverse event tracking. Patient questionnaires and stool sample analyses are also used to explore metabolic and microbiome changes over time.

Researchers are evaluating the safety and effectiveness of two drugs, 64Cu-SAR-bisPSMA and 67Cu-SAR-bisPSMA, in men with prostate cancer that has spread and no longer responds to hormone-lowering treatments. This study focuses on cancers that express a protein called PSMA and aims to find safe and effective dosing while monitoring how the drugs behave in the body. Participants will go through different study phases. In the initial dosimetry phase, a single dose of 200 MBq of 64Cu-SAR-bisPSMA is given. Later phases involve receiving multiple doses of 64Cu-SAR-bisPSMA or 67Cu-SAR-bisPSMA, with doses and number of administrations varying by phase and participant group. The dose escalation phase tests increasing doses of 67Cu-SAR-bisPSMA, followed by a cohort expansion phase with up to six doses of the recommended 67Cu-SAR-bisPSMA dose. During the study, participants will undergo PET/CT scans to track drug distribution and dosimetry within 48 hours of dosing. Researchers will measure prostate-specific antigen (PSA) levels and radiographic responses over up to five years to evaluate treatment effects. Safety will be monitored through assessments of vital signs, ECGs, laboratory tests, and recording any adverse events. The total study duration can extend up to five years for long-term follow-up.

Researchers are evaluating the safety and effectiveness of ifinatamab deruxtecan (I-DXd), alone or combined with other treatments, for people with metastatic castration-resistant prostate cancer (mCRPC). This study aims to find a safe dose of I-DXd in combination with other therapies and to monitor prostate specific antigen (PSA) levels during treatment. It is a phase 1/2, open-label study under the MK-2400-U01 master protocol. Participants may receive one of several treatments: docetaxel given intravenously every three weeks for up to 10 cycles; I-DXd alone administered intravenously every three weeks until side effects, disease progression, death, or withdrawal; I-DXd combined with MK-5684 taken orally; or I-DXd combined with an androgen receptor pathway inhibitor (either abiraterone acetate or enzalutamide) taken orally. The study includes a dose escalation phase followed by longer treatment periods. During the study, participants will be monitored for treatment side effects, PSA response, and other outcomes such as disease progression and survival over several years. Researchers will track adverse events, dose-limiting toxicities, and reasons for stopping treatment. The total follow-up may last up to about 54 months, with regular assessments including safety, efficacy, and quality of life measures.

Researchers are studying a new treatment approach for patients with surgically removable head and neck squamous cell carcinoma (HNSCC), a common and serious type of cancer in the head and neck region. The study evaluates the safety and tolerability of combining immune-targeted therapy with a lysogenic herpes simplex virus (HSV) as a neoadjuvant treatment to reduce tumor size before surgery. This innovative combination aims to improve surgery outcomes and lower the chances of cancer returning or spreading. Participants receive a combination of treatments including Tislelizumab given on days 1 and 22, and continuous daily Afatinib from days 1 to 42. They also receive injections of the lysogenic HSV virus directly into lymph nodes, with dosing based on lymph node size, given twice two weeks apart. After these treatments, patients undergo standard surgical removal of the tumor. The HSV virus injection includes an initial dose-escalation phase followed by a dose-expansion phase to find the most effective dose. During the study, patients are closely monitored for side effects and treatment tolerance, including checking for dose-limiting toxicities during surgery. Researchers will assess how well the tumor responds to treatment by examining major and complete pathological responses and overall tumor shrinkage up to eight weeks after treatment. They will also monitor adverse events for up to 12 weeks and follow disease-free survival for one year. The study duration and procedures are planned to provide detailed information on the safety and effects of this combined therapy.

Researchers are evaluating the safety and effectiveness of a new neoadjuvant treatment combining Cadonilimab, a PD-1/CTLA-4 bispecific antibody, with platinum-based chemotherapy (Paclitaxel Polymeric Micelles for Injection and Cisplatin) for patients with locally advanced esophageal squamous cell carcinoma. This Phase 2 clinical trial aims to measure pathologic complete remission rates after 2 to 4 treatment cycles, alongside other measures like objective remission rate, major pathologic remission rate, surgical removal rate, and 2-year survival outcomes. Participants receive Cadonilimab intravenously at 10 mg/kg on day 3 every 3 weeks, combined with Paclitaxel Polymeric Micelles administered intravenously (230 mg/m2 for cycle 1; possibly increased to 260 mg/m2 for cycles 2-4 depending on blood counts and side effects) and Cisplatin intravenously at 25 mg/m2 daily for 3 days every 3 weeks. Treatment lasts approximately 12 weeks, covering 2 to 4 cycles before surgery. Throughout the study, participants undergo regular assessments including pathological evaluation after surgery to determine remission, as well as monitoring of overall and progression-free survival over 2 years. Safety and organ function are closely observed, with eligibility requiring adequate heart, liver, kidney, and blood function. Participants are followed from treatment initiation through surgery and beyond to evaluate clinical outcomes and side effects.

Researchers are evaluating the effects of Poly L-lactic Acid (PLLA) biostimulator treatment on women at various menopausal stages who have moderate-to-severe cheek wrinkles. This randomized, prospective study aims to assess changes in protein expression in the skin after treatment, using punch biopsies taken at several follow-up visits compared to baseline. The study is sponsored by Galderma R&D and involves about 40 participants across two sites. Participants will receive Sculptraae, a biostimulator device, applied to both cheeks in up to three treatments spaced four weeks apart. Initially, a punch biopsy is taken on one pre-auricular cheek side at baseline. After the first and second treatments, participants may receive a third optional treatment at week 8. At 12 weeks after the last Sculptra treatment, half of the subjects will have a second punch biopsy on the opposite cheek side, with the rest receiving this biopsy at 36 weeks post-treatment. Follow-up visits occur at 24 weeks after the final treatment. During the study, participants will be monitored through physical assessments, biopsy procedures, and self-assessment questionnaires measuring satisfaction at 12, 24, and 36 weeks after treatment. Researchers will analyze protein expression changes and track participant experiences. The study includes safety and adherence monitoring throughout the treatment and follow-up period, lasting up to 36 weeks after the last Sculptra treatment.

Researchers are evaluating a combination of immune-targeted therapy and lysogenic herpes simplex virus (HSV) virotherapy as a neoadjuvant treatment for patients with surgically resectable head and neck squamous cell carcinoma (HNSCC). This study aims to improve surgical success and reduce the risk of recurrence and metastasis by using these therapies before surgery. The trial is a prospective, single-arm study focused on the safety and tolerability of this innovative approach for patients with locally advanced HNSCC without distant metastasis. Participants will receive tislelizumab on days 1 and 22, afatinib daily from days 1 to 42, and injections of lysogenic HSV virus into lymph nodes in two doses spaced two weeks apart. The virus dose will be adjusted based on lymph node size, with a dose-escalation phase followed by a dose-expansion phase using the most effective dose. After these treatments, patients will undergo standard surgery to remove the tumor. During the study, researchers will monitor participants for dose-limiting toxicities during surgery and evaluate responses such as major pathologic response and complete pathologic response. Additional assessments include adverse events up to 12 weeks, objective response rate up to 8 weeks, and one-year disease-free survival. Participants will attend scheduled visits for treatment administration, surgery, and follow-up to assess safety and treatment effects throughout the trial period.