NCT03516812

Testosterone and Olaparib in Treating Patients With Castration-Resistant Prostate Cancer

Bipolar Androgen Therapy Plus Olaparib in Patient With Castration-Resistant Prostate Cancer

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 36 (actual)
• Sponsor: University of Washington · Academic / Other
• Sex: Male
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial studies how well testosterone (enanthate or cypionate) and olaparib work in treating patients with prostate cancer that has progressed despite hormonal therapy. Hormonal therapy, such as leuprolide, may lessen the amount of male sex hormones made by the body. In patients that have developed progressive cancer in spite of standard hormonal treatment (i.e. castration-resistant prostate cancer), administering testosterone may result in regression of tumors by causing DNA damage in cancer cells that have adapted to low testosterone conditions. Olaparib may stop the growth of tumor cells by blocking some of the enzymes involved in repairing DNA damage. Therefore, giving testosterone and olaparib together may work better in treating castration-resistant prostate cancer by generating DNA damage that the cancer cell is unable to repair.

Detailed description

PRIMARY OBJECTIVE: I. Determine the prostate-specific antigen (PSA)50 response rate (i.e., percent of patients with a PSA decline of at least 50% below baseline) following 12-weeks of treatment with bipolar androgen therapy (BAT) plus olaparib in men with asymptomatic metastatic castration-resistant prostate cancer (mCRPC) who have progressed on abiraterone and/or enzalutamide. SECONDARY OBJECTIVES: I. Determine the percent of mCRPC patients achieving a radiographic response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria following treatment with BAT plus olaparib. II. Determine the radiographic progression free survival (PFS) in mCRPC patients treated with BAT plus olaparib using RECIST 1.1 criteria for soft tissue metastases and Prostate Cancer Working Group 3 (PCWG3) criteria for bone metastases. III. Determine the PSA PFS rate according to PCWG3 criteria in mCRPC patients treated with BAT plus olaparib. IV. Determine the PFS (i.e. whichever occurs first: clinical, radiographic or PSA progression) in mCRPC patients treated with BAT plus olaparib. V. Determine the overall survival in mCRPC patients treated with BAT plus olaparib. VI. Track changes in quality of life (QoL) as determined using the Functional Assessment of Cancer Therapy -Prostate (FACT-P) and International Index of Erectile Function (IIEF) surveys. VII. Assess the incidence and severity of adverse events according to the National Cancer Institute - Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. EXPLORATORY OBJECTIVES: I. Evaluate for differences in response and PFS in patients with/without mutations in genes involved in homologous recombination. II. Determine intratumoral androgen levels using liquid chromatography-mass spectrometry (LC/MS). III. Assess for evidence of double stranded deoxyribonucleic acid (dsDNA) breaks using gamma-H2AX immunostaining on circulating tumor cells (CTCs) and metastatic tissue. IV. Assess androgen receptor (AR) and AR splice variant (AR-V) transcript expression levels using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) on CTCs. V. Assess androgen receptor (AR) and AR splice variant (AR-V) protein expression levels using immunostaining on circulating tumor cells (CTCs) and metastatic tissue. VI. Sequence tumor DNA (cell-free circulating tumor DNA \[ctDNA\] and/or metastatic tissue). VII. Conduct transcript profiling studies on CTCs (multiplexed qRT-PCR) and metastatic tissue (ribonucleic acid sequencing \[RNA-seq\]). OUTLINE: Patients receive olaparib orally (PO) twice daily (BID) on days 1-28 and testosterone enanthate or cypionate intramuscularly (IM) on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of the study treatment, patients are followed up at 30 days and every 6 months for up to 2 years.

Conditions

• Castration-Resistant Prostate Carcinoma
• Prostate Adenocarcinoma

Interventions

Type	Name	Description
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Olaparib	Given PO
OTHER	Quality-of-Life Assessment	Ancillary studies
OTHER	Survey Administration	Ancillary studies
DRUG	Testosterone Enanthate	Given IM
DRUG	Testosterone Cypionate	Given IM

Timeline

• Start date: 2018-08-29
• Primary completion: 2021-03-05
• Completion: 2024-04-12
• First posted: 2018-05-04
• Last updated: 2025-09-29
• Results posted: 2022-05-18

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study