This phase II trial tests how well eflornithine and testosterone cypionate followed by enzalutamide works in treating patients with prostate cancer that has spread from where it first started (primary site) to other places in the body (metastatic) and that grows and continues to spread despite treatment to lower testosterone in the blood (castration-resistant). Eflornithine inhibits an enzyme required for tumor cell formation and proliferation and it has been shown to cause death in some types of tumor cells. Testosterone cypionate is a synthetic form of testosterone. It can be used to increase testosterone levels in men who do not make enough testosterone on their own. Enzalutamide blocks testosterone in prostate tumor cells by inhibiting the activity of androgen receptors on the cells. This may lead to a reduction in prostate tumor cell proliferation and a reduction in the serum prostate specific antigen level. Research has shown that castration-resistant prostate cancer cells can be killed by high levels of testosterone followed by a rapid drop to low testosterone levels. This is called bipolar androgen therapy. After bipolar androgen therapy, many patients show improved response to treatment with enzalutamide. Giving eflornithine and testosterone cypionate together may be more effective in blocking prostate tumor growth than either drug alone and may make castration-resistant prostate tumor cells more sensitive to treatment with enzalutamide.
Additional locations may be listed on ClinicalTrials.gov for NCT06059118.
Locations matching your search criteria
United States
Maryland
Baltimore
Johns Hopkins University/Sidney Kimmel Cancer CenterStatus: Active
Contact: Laura Sena
Phone: 410-502-3825
PRIMARY OBJECTIVE:
I. To determine if treatment with the combination of eflornithine (DFMO) plus bipolar androgen therapy (BAT) improves prostate specific antigen (PSA) response in asymptomatic patients with evidence of progressive metastatic castration resistant prostate cancer (CRPC) post-treatment with a second-generation androgen receptor (AR)-axis inhibitor (abiraterone, enzalutamide, darolutamide, or apalutamide) compared to historical controls.
SECONDARY OBJECTIVES:
I. Progression–free survival (PFS): time to radiographic or clinical progression or death (Prostate Cancer Clinical Trials Working Group 3 [PCWG3] definition).
II. PSA response rate (> 50% PSA decline from baseline) at any point on trial.
III. Incidence and severity of adverse events and serious adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0.
IV. PSA progression–free survival (PSA–PFS) (PCWG3 criteria).
V. Objective response rate in those with measurable disease.
VI. Change in pain score on the modified Patient Reported Outcomes Measurement Information System (PROMIS) Short Form (SF) v.1.0 short forms 3a and 6b.
VII. Overall survival.
OUTLINE:
Patients receive DFMO orally (PO) twice daily (BID) on days 1-63 of each cycle, testosterone cypionate intramuscularly (IM) on days 8 and 36 of each cycle, and enzalutamide PO once daily (QD) on days 64-119 of each cycle. Cycles repeat every 119 days in the absence of disease progression or unacceptable toxicity. Patients also continue receiving anti-androgen therapy (ADT) with luteinizing hormone-releasing hormone (LHRH) agonist or LHRH antagonist for the duration of the study if not surgically castrated. Patients also undergo computed tomography (CT), bone scan and collection of blood samples throughout the trial. Patients may also undergo biopsy throughout the trial.
After completion of study treatment, patients are followed up within 1 week and then every 6 months for up to 3 years.
Lead OrganizationJohns Hopkins University/Sidney Kimmel Cancer Center
Principal InvestigatorLaura Sena