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

• Sponsor: University of Washington (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03516812
• Collaborator: National Cancer Institute (NCI) (NIH), AstraZeneca (Industry)
• Enrollment: 36
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 54.3
• Patients Per Site Per Month: 0.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Castration-Resistant Prostate Carcinoma; Prostate Adenocarcinoma	Other: Laboratory Biomarker Analysis; Drug: Olaparib; Other: Quality-of-Life Assessment; Other: Survey Administration; Drug: Testosterone Enanthate; Drug: Testosterone Cypionate	Phase 2

Detailed Description

PRIMARY OBJECTIVE:

1. 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:

1. 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.

2. 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.

3. Determine the PSA PFS rate according to PCWG3 criteria in mCRPC patients treated with BAT plus olaparib.

4. Determine the PFS (i.e. whichever occurs first: clinical, radiographic or PSA progression) in mCRPC patients treated with BAT plus olaparib.

5. Determine the overall survival in mCRPC patients treated with BAT plus olaparib.

6. 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.

7. 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:

1. Evaluate for differences in response and PFS in patients with/without mutations in genes involved in homologous recombination.

2. Determine intratumoral androgen levels using liquid chromatography-mass spectrometry (LC/MS).

3. Assess for evidence of double stranded deoxyribonucleic acid (dsDNA) breaks using gamma-H2AX immunostaining on circulating tumor cells (CTCs) and metastatic tissue.

4. Assess androgen receptor (AR) and AR splice variant (AR-V) transcript expression levels using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) on CTCs.

5. Assess androgen receptor (AR) and AR splice variant (AR-V) protein expression levels using immunostaining on circulating tumor cells (CTCs) and metastatic tissue.

6. Sequence tumor DNA (cell-free circulating tumor DNA [ctDNA] and/or metastatic tissue).

7. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Bipolar Androgen Therapy Plus Olaparib in Patient With Castration-Resistant Prostate Cancer
• Actual Study Start Date: Aug 29, 2018
• Actual Primary Completion Date: Mar 5, 2021
• Anticipated Study Completion Date: Mar 8, 2023

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (olaparib, testosterone enanthate or cypionate) 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; Correlative studies; Drug: Olaparib; Given PO; Other Names: AZD2281 KU-0059436 Lynparza PARP Inhibitor AZD2281 ; Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment ; Other: Survey Administration; Ancillary studies; Drug: Testosterone Enanthate; Given IM; Other Names: Andro LA Androtardyl Delatestryl Everone Primosteston Testate Testinon Testo-Enant ; Drug: Testosterone Cypionate; Given IM; Other Names: Depo-Testosterone TC TCPP Testosterone cyclopentylpropionate Testosterone cyclopentanepropionate Testosterone 17β-cyclopentylpropionate

Outcome Measures

Primary Outcome Measures

1. Percent of Patients With a Prostate-specific Antigen (PSA) Decline of at Least 50% Below Baseline PSA50 Response Rate [Median time to PSA50 response was 22 weeks.]

   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.

Secondary Outcome Measures

1. 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]

   Safety will be summarized as the severity and frequency of a given AE.

2. Radiographic Response Rate [Up to 2 years]

   Per the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines, a radiographic response (as determined on CT or MRI) will be defined as: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

3. PSA Progression Free Survival (PFS) [From the start of treatment until PSA progression, assessed up to 2 years]

   This will be defined by Prostate Cancer Working Group 3 criteria. Survival endpoints will be presented with Kaplan-Meier curves, and the median survival with 95% CI will be calculated. Rates will be reported as percentages with 95% CI. Best on study PSA for each patient will be presented in a waterfall plot.

4. Overall Survival (OS) [Up to 2 years]

   Survival endpoints will be presented with Kaplan-Meier curves, and the median survival with 95% CI will be calculated. Rates will be reported as percentages with 95% CI.

5. Radiographic PFS [Up to 2 years]

   Will be presented in a waterfall plot.

6. Average Change in Quality of Life (QOL) Assessed by the Functional Assessment of Cancer Therapy-Prostate (FACT-P) Survey [Up to 2 years after initiating therapy]

   Average change in QOL scores (total and for each domain) for each survey will be calculated at each timepoint. A paired t-test will be used to assess for statistically significant changes in QOL from baseline to the 12-week timepoint, and linear mixed effects models will be used to evaluate trends over all timepoints.

7. Average Change in Quality of Life (QOL) Assessed by the International Index of Erectile Function (IIEF) Survey [Up to 2 years after initiating therapy]

   Average change in QOL scores (total and for each domain) for each survey will be calculated at each timepoint. A paired t-test will be used to assess for statistically significant changes in QOL from baseline to the 12-week timepoint, and linear mixed effects models will be used to evaluate trends over all timepoints.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 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

• Male patients and their partners, who are sexually active and of childbearing potential, must agree to the use of two highly effective forms of contraception in combination throughout the period of taking study treatment and for 3 months after last dose of study drug(s) to prevent pregnancy in a partner

• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations

• At least one lesion (measurable and/or non-measurable) that can be accurately assessed at baseline by computed tomography (CT), positron-emission tomography (PET), magnetic resonance imaging (MRI) and/or bone scan and is suitable for repeated assessment

• Must have archival tissue available, be willing to undergo metastatic biopsy or have a sufficient plasma circulating tumor DNA (ctDNA) concentration in order to perform next-generation DNA sequencing

• The study will require that 50% of enrolled subjects have homozygous deletions, deleterious mutations, or both in one or more of the DNA damage response (DDR) genes; the other 50% of patients must have an intact DDR pathway

Exclusion Criteria:

• 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

1. 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

• Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV)

• Patients with a known hypersensitivity to olaparib or any of the excipients of the product

• Patients with a known hypersensitivity to the testosterone cypionate or any of the excipients of the product

• Patients with known active hepatitis (i.e., hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids

• Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)

• Whole blood transfusions in the last 120 days prior to entry to the study (packed red blood cells and platelet transfusions are acceptable)

• Evidence of serious and/or unstable pre-existing medical, psychiatric or other condition (including laboratory abnormalities) that could interfere with patient safety or provision of informed consent to participate in this study

• Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule

• Evidence of disease that, in the opinion of the investigator, would put the patient at risk from testosterone therapy (e.g. femoral metastases with concern over fracture risk, spinal metastases with concern over spinal cord compression, lymph node disease with concern for ureteral obstruction)

• Patients with pain attributable to their prostate cancer

• Tumor causing urinary outlet obstruction that requires catheterization for voiding; patients that require catheterization to void secondary to benign strictures or other non-cancer causes will be permitted to enroll

• Prior history of deep venous thrombosis or pulmonary embolism within 5 years prior to enrollment in the study and not currently on systemic anticoagulation

• Patients with NYHA (New York Heart Association) class III or IV heart failure or history of a prior myocardial infarction (MI) prior to enrollment in the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington	United States	98109

Sponsors and Collaborators

• University of Washington
• National Cancer Institute (NCI)
• AstraZeneca

Investigators

• Principal Investigator: Michael T. Schweizer, Fred Hutch/University of Washington Cancer Consortium

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 25, 2021

More Information

Publications

None provided.

• Responsible Party: Michael Schweizer, Associate Professor, Division of Medical Oncology, University of Washington
• ClinicalTrials.gov Identifier: NCT03516812
• Other Study ID Numbers: 9984; NCI-2018-00542; 9984; P30CA015704; RG1718004
• First Posted: May 4, 2018
• Last Update Posted: May 18, 2022
• Last Verified: Apr 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Prostatic Neoplasms; Adenocarcinoma; Methyltestosterone; Olaparib; Poly(ADP-ribose) Polymerase Inhibitors; Testosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate

Study Results

Participant Flow

Arm/Group Title	Treatment (Olaparib, Testosterone Enanthate or Cypionate)
Arm/Group Description	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. Laboratory Biomarker Analysis: Correlative studies Olaparib: Given PO Quality-of-Life Assessment: Ancillary studies Survey Administration: Ancillary studies Testosterone Enanthate: Given IM Testosterone Cypionate: Given IM
Period Title: Overall Study
STARTED	36
COMPLETED	30
NOT COMPLETED	6

Baseline Characteristics

Arm/Group Title	Treatment (Olaparib, Testosterone Enanthate or Cypionate)
Arm/Group Description	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. Laboratory Biomarker Analysis: Correlative studies Olaparib: Given PO Quality-of-Life Assessment: Ancillary studies Survey Administration: Ancillary studies Testosterone Enanthate: Given IM Testosterone Cypionate: Given IM
Overall Participants	36
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	70.1
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	36 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	1 2.8%
Black or African American	1 2.8%
White	25 69.4%
More than one race	0 0%
Unknown or Not Reported	9 25%
PSA (ng/ml) [Median (Full Range) ]
Median (Full Range) [ng/ml]	25.6
Prior abiraterone treatment (Count of Participants)
Count of Participants [Participants]	25 69.4%
Prior enzalutamide treatment (Count of Participants)
Count of Participants [Participants]	18 50%
Prior docetaxel treatment (Count of Participants)
Count of Participants [Participants]	9 25%

Outcome Measures

1. Primary Outcome

Title	Percent of Patients With a Prostate-specific Antigen (PSA) Decline of at Least 50% Below Baseline PSA50 Response Rate
Description	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.
Time Frame	Median time to PSA50 response was 22 weeks.

Outcome Measure Data

Analysis Population Description

Includes patient that received at least 12 weeks of treatment.

Arm/Group Title	Treatment (Olaparib, Testosterone Enanthate or Cypionate)
Arm/Group Description	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. Laboratory Biomarker Analysis: Correlative studies Olaparib: Given PO Quality-of-Life Assessment: Ancillary studies Survey Administration: Ancillary studies Testosterone Enanthate: Given IM Testosterone Cypionate: Given IM
Measure Participants	30
Count of Participants [Participants]	14 38.9%

2. Secondary Outcome

Title	Incidence of Adverse Events (AEs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03
Description	Safety will be summarized as the severity and frequency of a given AE.
Time Frame	Up to 30 days after last dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Radiographic Response Rate
Description	Per the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines, a radiographic response (as determined on CT or MRI) will be defined as: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Olaparib, Testosterone Enanthate or Cypionate)
Arm/Group Description	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. Laboratory Biomarker Analysis: Correlative studies Olaparib: Given PO Quality-of-Life Assessment: Ancillary studies Survey Administration: Ancillary studies Testosterone Enanthate: Given IM Testosterone Cypionate: Given IM
Measure Participants	13
Count of Participants [Participants]	8 22.2%

4. Secondary Outcome

Title	PSA Progression Free Survival (PFS)
Description	This will be defined by Prostate Cancer Working Group 3 criteria. Survival endpoints will be presented with Kaplan-Meier curves, and the median survival with 95% CI will be calculated. Rates will be reported as percentages with 95% CI. Best on study PSA for each patient will be presented in a waterfall plot.
Time Frame	From the start of treatment until PSA progression, assessed up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Overall Survival (OS)
Description	Survival endpoints will be presented with Kaplan-Meier curves, and the median survival with 95% CI will be calculated. Rates will be reported as percentages with 95% CI.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Radiographic PFS
Description	Will be presented in a waterfall plot.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Average Change in Quality of Life (QOL) Assessed by the Functional Assessment of Cancer Therapy-Prostate (FACT-P) Survey
Description	Average change in QOL scores (total and for each domain) for each survey will be calculated at each timepoint. A paired t-test will be used to assess for statistically significant changes in QOL from baseline to the 12-week timepoint, and linear mixed effects models will be used to evaluate trends over all timepoints.
Time Frame	Up to 2 years after initiating therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	Average Change in Quality of Life (QOL) Assessed by the International Index of Erectile Function (IIEF) Survey
Description	Average change in QOL scores (total and for each domain) for each survey will be calculated at each timepoint. A paired t-test will be used to assess for statistically significant changes in QOL from baseline to the 12-week timepoint, and linear mixed effects models will be used to evaluate trends over all timepoints.
Time Frame	Up to 2 years after initiating therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Up to 2 years
Arm/Group Title	Treatment (Olaparib, Testosterone Enanthate or Cypionate)
Arm/Group Description	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. Laboratory Biomarker Analysis: Correlative studies Olaparib: Given PO Quality-of-Life Assessment: Ancillary studies Survey Administration: Ancillary studies Testosterone Enanthate: Given IM Testosterone Cypionate: Given IM
All Cause Mortality
	Treatment (Olaparib, Testosterone Enanthate or Cypionate)
	Affected / at Risk (%)	# Events
Total	2/36 (5.6%)
Serious Adverse Events
	Treatment (Olaparib, Testosterone Enanthate or Cypionate)
	Affected / at Risk (%)	# Events
Total	5/36 (13.9%)
Cardiac disorders
Myocardial infarction	1/36 (2.8%)
Musculoskeletal and connective tissue disorders
Rib fracture	1/36 (2.8%)
Nervous system disorders
Subdural hematoma	1/36 (2.8%)
Stroke	1/36 (2.8%)
Cord compression	1/36 (2.8%)
Other (Not Including Serious) Adverse Events
	Treatment (Olaparib, Testosterone Enanthate or Cypionate)
	Affected / at Risk (%)	# Events
Total	33/36 (91.7%)
Blood and lymphatic system disorders
Anemia	7/36 (19.4%)
Edema	2/36 (5.6%)
Gastrointestinal disorders
Nausea	18/36 (50%)
Constipation	8/36 (22.2%)
Vomiting	6/36 (16.7%)
Diarrhea	4/36 (11.1%)
Abdominal pain	2/36 (5.6%)
General disorders
Fatigue	21/36 (58.3%)
Pain	13/36 (36.1%)
Metabolism and nutrition disorders
Anorexia	7/36 (19.4%)
Weight loss	3/36 (8.3%)
Hypercalcemia	2/36 (5.6%)
Nervous system disorders
Dysgeusia	5/36 (13.9%)
Dizziness or Lightheadedness	3/36 (8.3%)
Insomnia	2/36 (5.6%)
Memory impairment	2/36 (5.6%)
Renal and urinary disorders
Creatinine increase	4/36 (11.1%)
Nocturia	3/36 (8.3%)
Urinary retention	2/36 (5.6%)
Respiratory, thoracic and mediastinal disorders
Cough	3/36 (8.3%)
Vascular disorders
Thromboembolic event	2/36 (5.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.