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

NCT03516812 | Completed Phase 2 Results DMC FDA Drug

• 4 other identifiers: 9984NCI-2018-00542P30CA015704RG1718004
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Castration-Resistant Prostate Carcinoma; Prostate Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Percent of Patients With a Prostate-specific Antigen (PSA) Decline of at Least 50% Below Baseline PSA50 Response Rate

  PSA response will be defined as a decline in PSA ≥ 50% compared to baseline in patients who received at least 12 weeks of treatment. Will be calculated as the percentage with 95% confidence interval (CI) of the total number of subjects that achieved a PSA response.

  Median time to PSA50 response was 22 weeks.

Secondary Outcomes (7)

• Incidence of Adverse Events (AEs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03

  Up to 30 days after last dose, 19 month median

• Radiographic Response Rate

  Up to 2 years

• PSA Progression Free Survival (PFS)

  Up to 2 years following the last dose of study drug, median of 20 months

• Overall Survival (OS)

  Up to 2 years following the last dose of study drug, median 29 months

• Radiographic PFS

  Up to 2 years following the last dose of study drug, median 19 months

Study Arms (1)

Treatment (olaparib, testosterone enanthate or cypionate)

EXPERIMENTAL

Patients receive olaparib PO BID on days 1-28 and testosterone enanthate or cypionate IM on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Drug: Olaparib; Other: Quality-of-Life Assessment; Other: Survey Administration; Drug: Testosterone Enanthate; Drug: Testosterone Cypionate

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (olaparib, testosterone enanthate or cypionate)

Olaparib DRUG

Given PO

Also known as: AZD2281, KU-0059436, Lynparza, PARP Inhibitor AZD2281

Treatment (olaparib, testosterone enanthate or cypionate)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (olaparib, testosterone enanthate or cypionate)

Survey Administration OTHER

Ancillary studies

Treatment (olaparib, testosterone enanthate or cypionate)

Testosterone Enanthate DRUG

Given IM

Also known as: Andro LA, Androtardyl, Delatestryl, Everone, Primosteston, Testate, Testinon, Testo-Enant

Treatment (olaparib, testosterone enanthate or cypionate)

Testosterone Cypionate DRUG

Given IM

Also known as: Depo-Testosterone, TC, TCPP, Testosterone cyclopentylpropionate, Testosterone cyclopentanepropionate, Testosterone 17β-cyclopentylpropionate

Treatment (olaparib, testosterone enanthate or cypionate)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must be willing to provide informed consent prior to any study specific procedures
• Documented histologically confirmed adenocarcinoma of the prostate
• Patient must have evidence of castration resistant prostate cancer as evidenced by PSA progression (per Prostate Cancer Working Group 3 \[PCWG3\] criteria) and a castrate serum testosterone level (i.e., ≤ 50 mg/dL)
• PSA must be at least 1 ng/ml and rising on two successive measurements at least two weeks apart
• Patients must have progressed on abiraterone and/or enzalutamide; there must be at least a 3-week washout period after stopping the most recent approved therapy for mCRPC (i.e., abiraterone, enzalutamide, Ra-223, sipuleucel-t); if applicable, patients should be weaned off steroids at least 1 week prior to starting treatment
• No prior chemotherapy for the treatment of mCRPC; patients may have received docetaxel for the treatment of hormone-sensitive prostate cancer
• Prior treatment with non-chemotherapy investigational agents is permitted; there must be at least a 3-week washout period after stopping any investigational cancer agent
• Hemoglobin ≥ 10.0 g/dL with no blood transfusion in the past 28 days (within 28 days prior to administration of study treatment)
• Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L (within 28 days prior to administration of study treatment)
• Platelet count ≥ 100 x 10\^9/L (within 28 days prior to administration of study treatment)
• Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (within 28 days prior to administration of study treatment)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase \[SGPT\]) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present in which case they must be ≤ 5 x ULN (within 28 days prior to administration of study treatment)
• Patients must have creatinine clearance estimated using the Cockcroft-Gault equation or based on a 24 hour urine test of ≥ 51 mL/min (within 28 days prior to administration of study treatment)
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Patients must have a life expectancy ≥ 16 weeks

You may not qualify if:

• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
• Previous enrollment in this study
• Participation in another clinical study with an investigational product during the last 3 weeks
• Any previous treatment with poly-adenosine diphosphate ribose polymerase (PARP) inhibitor, including olaparib
• Other malignancy unless curatively treated with no evidence of disease for ≥ 5 years except: adequately treated non-melanoma skin cancer
• Resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (e.g. unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, Fridericia's corrected QT interval \[QTcF\] prolongation \> 500 ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome
• Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment
• Concomitant use of known strong CYP3A inhibitors (e.g. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil); the required washout period prior to starting olaparib is 2 weeks
• Concomitant use of known strong (e.g. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's wort) or moderate CYP3A inducers (e.g. bosentan, efavirenz, modafinil); the required washout period prior to starting olaparib is 3 weeks for enzalutamide, 5 weeks for phenobarbital and 3 weeks for other agents
• Persistent toxicities (\> Common Terminology Criteria for Adverse Event \[CTCAE\] grade 2) caused by previous cancer therapy, excluding alopecia
• Patients with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)
• Patients with symptomatic uncontrolled brain metastases; a scan to confirm the absence of brain metastases is not required; the patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment; patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days
• Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery
• Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection; examples include, but are not limited to, uncontrolled ventricular arrhythmia, history of prior myocardial infarction, uncontrolled major seizure disorder, uncontrolled hypertension (blood pressure \[BP\] ≥ 160/100), history of prior stroke, uncontrolled diabetes (glycosylated hemoglobin \[hgb A1C\] \> 7), unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on high resolution computed tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent
• Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication

Sponsors & Collaborators

• University of Washington: lead
• National Cancer Institute (NCI): collaborator
• AstraZeneca: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Interventions

olaparib; testosterone enanthate; Testosterone Propionate; testosterone 17 beta-cypionate; tetracarboxyphenylporphine

Intervention Hierarchy (Ancestors)

Testosterone; Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Michael Schweizer
• Organization: University of Washington

schweize@uw.edu

206-606-6252

Study Officials

• Michael T. Schweizer

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Division of Medical Oncology

Study Record Dates

• First Submitted: April 19, 2018
• First Posted: May 4, 2018
• Study Start: August 29, 2018
• Primary Completion: March 5, 2021
• Study Completion: April 12, 2024
• Last Updated: September 29, 2025
• Results First Posted: May 18, 2022

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)