This phase II trial tests how well bipolar androgen therapy (BAT) with testosterone cypionate in combination with ZEN-3694 followed by the combination of enzalutamide and ZEN-3694 works in decreasing tumor size in patients with prostate cancer that has spread from where it first started to other places in the body (metastatic) and continues to grow and spread despite interventions to block hormone production (castration-resistant). Testosterone cypionate, a male hormone (an androgen), works by replacing the testosterone that is normally produced naturally in the body. BAT works by alternating between periods of high and low testosterone levels. This may keep the prostate tumor cells from adapting to low androgen levels and may improve sensitivity to treatment, as well as quality of life and sexual function. ZEN-3694 is an inhibitor of a family of proteins called the bromodomain and extra-terminal (BET). It may prevent the growth of tumor cells that over produce BET protein. Enzalutamide, a type of antiandrogen, binds to proteins called androgen receptors (AR), which are found in some prostate tumor cells. These proteins bind to androgens and may cause tumor cells to grow. Enzalutamide blocks these proteins and may keep tumor cells from growing. Giving BAT with testosterone cypionate in combination with ZEN-3694 followed by the combination of enzalutamide and ZEN-3694 may decrease tumor size and improve survival in patients with asymptomatic metastatic castration-resistant prostate cancer (CRPC).
Additional locations may be listed on ClinicalTrials.gov for NCT06922318.
Locations matching your search criteria
United States
Maryland
Baltimore
Johns Hopkins University/Sidney Kimmel Cancer CenterStatus: Active
Contact: Samuel Ray Denmeade
Phone: 410-502-8341
PRIMARY OBJECTIVES:
I. To determine if treatment with the combination of BAT plus BET bromodomain inhibitor ZEN-3694 (ZEN-3694) (BATZEN) improves clinical/radiographic progression free survival (PFS) in asymptomatic patients with evidence of progressive metastatic CRPC post-treatment with a second-generation AR-axis inhibitor (abiraterone, enzalutamide, darolutamide, or apalutamide) compared to historical controls.
II. To determine if treatment with ZEN-3694 and enzalutamide (i.e. ZENZA) after progression on BAT will improve prostate specific antigen (PSA) progression free survival (PFS) compared to historical controls.
SECONDARY OBJECTIVES:
I. PSA50 response to BATZEN (≥ 50% PSA reduction from baseline level at screening).
II. PSA50 response to ZENZA (≥ 50% PSA reduction from PSA level at time of progression on BATZEN).
III. Time to PSA progression while on BATZEN.
IV. Objective response to BATZEN and ZENZA, respectively per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
V. PFS2 (time from start of BATZEN to date of PSA progression on ZENZA).
VI. Overall survival.
VII. Quality of life (Functional Assessment of Chronic Illness Therapy [FACIT]-Fatigue, Short Form [SF]-36).
VIII. Safety and tolerability.
OUTLINE:
BATZEN: Patients receive testosterone cypionate intramuscularly (IM) on day 1 of each cycle and ZEN-3694 orally (PO) once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also continue receiving androgen deprivation therapy (ADT) with luteinising hormone-releasing hormone (LHRH) agonists (Zoladex, Trelstar, Eligard or Lupron) or LHRH antagonists (degarelix or relugolix) if not surgically castrated throughout the study.
ZENZA: Starting at time of disease progression, patients receive enzalutamide PO QD on days 1-28 and an increased dose of ZEN-3694 PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also continue receiving ADT therapy with LHRH agonists (Zoladex, Trelstar, Eligard or Lupron) or LHRH antagonists (degarelix or relugolix) if not surgically castrated throughout the study.
Patients also undergo bone scan, computed tomography (CT), and blood sample collection throughout the study. Additionally, patients with soft tissue lesions also undergo a biopsy throughout the study.
After completion of study treatment, patient are followed up at 30 days then every 6 months for up to 3 years.
Lead OrganizationJohns Hopkins University/Sidney Kimmel Cancer Center
Principal InvestigatorSamuel Ray Denmeade