Testosterone Revival Abolishes Negative Symptoms, Fosters... | NCT02286921

NCT02286921

ID	Type	Description	Link
IRB00046414	Other Identifier	JHU IRB
W81XWH-14-2-0189	Other Grant/Funding Number	Department of Defense

Status Module

Sponsor/Collaborators Module

Name	Class
United States Department of Defense	FED

Oversight Module

Description Module

Detailed Description

Eligible patients will have metastatic CRPC with no disease related symptoms and progression on Androgen deprivation therapy and will have progressed post-treatment with abiraterone. Patients will continue on Androgen deprivation therapy with Luteinising Hormone Releasing Hormone agonist (i.e. Zoladex, Trelstar, Eligard or Lupron) or Luteinising Hormone Releasing Hormone antagonist (Degarelix) if not surgically castrated throughout the duration of the study to inhibit endogenous testosterone production. Patients will be randomized 1:1 and stratified based on duration of prior abiraterone acetate therapy (6 months or less or greater than 6 months). Patients randomized to BAT (Arm A) will receive intramuscular injections with either testosterone cypionate or testosterone enanthate at a dose of 400 mg every 28 days. This dose was selected based on data demonstrating that it produces an initial supraphysiologic serum level of T (i.e. > 1500 ng/dL or 3-10 times normal level) with eugonadal levels achieved at the end of two weeks and near castrate levels after 28 days. Patients randomized to enzalutamide (Arm B) will receive daily oral dose of 160 mg. Each cycle is defined as 28 days.

Patients will have Prostate-specific antigen level and symptoms assessment checked every cycle. Every 3 cycles patients will have repeat bone/CT scans to evaluate treatment response status. On CT scan, radiographic progression will be defined by RECIST criteria (i.e. >20% increase in the sum of target lesions). On bone scan, radiographic progression will be defined by PCWG2 criteria as ≥ 2 new bone lesions. However, for the first reassessment scan only, patients should remain on study and have a confirmatory scan performed 12 weeks (3 cycles) later. If this confirmatory scan shows 2 or more additional new lesions, this defines progression. The date of progression is the date of the first reassessment bone scan. If the confirmatory scan does not show any additional new lesions, patient remains on study. If progression is observed on subsequent bone scans, a confirmatory scan is not required; the date of this bone scan is the date of progression.

Patients with Prostate-specific antigen progression but with disease response or stable disease on imaging studies will remain on study until radiographic or other clinical progression criteria are met. Patients with radiographic disease progression will not receive continued BAT (arm A) or enzalutamide (arm B) and will be eligible for crossover to the opposite therapy. Patients on the BAT arm A can cross over to receive enzalutamide at time of progression or can choose to go off study and be treated with other standard of care treatments. Patients on the enzalutamide arm B will be allowed to cross-over to receive BAT or can choose to go off study and be treated with other standard of care treatments.

Patients with clinical progression due to prostate cancer must meet study exclusion criteria to be permitted to cross-over to the opposite treatment. Patients with clinical progression due to pain from prostate cancer are not permitted to cross-over.

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Arm A: Testosterone cypionate or testosterone enanthate	Experimental	Patients on BAT will receive testosterone cypionate or testosterone enanthate administered as an intramuscular injection. A dose of 400 mg of either agent will be injected intramuscularly (IM) every 28 days.	Drug: Testosterone cypionate Drug: Testosterone Enanthate
Arm B: Enzalutamide	Experimental	Patients randomized to enzalutamide will be prescribed enzalutamide 40 mg tablets and instructed to take 4 tablets per day orally for 28 days/cycle.	Drug: Enzalutamide

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Testosterone cypionate	Drug	Depo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble of the androgenic hormone testosterone. Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. Depo-Testosterone Injection is available in two strengths, 100 mg/mL and 200 mg/mL testosterone cypionate.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Progression Free Survival as Measured by Number of Months Until Clinical or Radiographic Progression	Time to clinical progression will be defined as months from randomization to any of the following (whichever occurs earlier): Cancer pain requiring initiation of chronic administration of opiate analgesia (oral opiate use for ≥3 weeks; parenteral opiate use for ≥7 days. Patients with cancer pain requiring opiate analgesia for relief should also be assessed by the investigator for the need for initiating systemic chemotherapy or palliative radiation. Development of a skeletal-related event (SRE): pathologic fracture, spinal cord compression, or need for surgical intervention or radiation therapy to the bone. Development of clinically significant symptoms due to loco-regional tumor progression (e.g. urinary obstruction) requiring surgical intervention or radiation therapy.	up to 2 years

Secondary Outcomes

Measure	Description	Time Frame
Radiographic Progression	Number of months until 20% increase in the sum of target lesions on CT scans.	up to 2 years
Prostate-Specific Antigen Response Rate	Number of participants achieving a Prostate-Specific Antigen decline ≥ 50% according to Prostate Cancer Working Group (PCWG2) criteria.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Eastern Cooperative Oncology Group Performance status ≤2
Age ≥18 years
Histologically-confirmed adenocarcinoma of the prostate
Treated with continuous androgen ablative therapy (either surgical castration or luteinizing hormone-releasing hormone agonist/antagonist)
Documented castrate level of serum testosterone (<50 ng/dl)
Metastatic disease radiographically documented by CT/MRI or bone scan.
Must have had disease progression while on abiraterone acetate alone or abiraterone acetate in combination with other investigational agents based on:
- Prostate-specific antigen progression defined as an increase in Prostate-specific antigen, as determined by 2 separate measurements taken at least 1 week apart

And/Or

Radiographic disease progression, based on RECIST 1.1 in patients with measurable soft tissue lesions, or PCWG2 for patients with bone disease
- Screening Prostate-specific antigen must be ≥ 1.0 ng/mL.
- Prior treatment with additional second line hormone therapies is allowed.
- No prior treatment with enzalutamide, Apalutamide (ARN-509), Darolutamide (ODM-201), galeterone or other investigational androgen receptor targeted treatment is allowed.
- Prior docetaxel for hormone-sensitive prostate cancer is permitted if ≤ 6 doses were given in conjunction with first-line androgen deprivation therapy and >12 months since last dose of docetaxel.
- Prior treatment with Provenge vaccine and 223Radium (Xofigo) is allowed if >4 weeks from last dose.
- Patients must be withdrawn from abiraterone for ≥ 2 weeks.
- Patients must be weaned off prednisone and be off therapy for ≥ 1 week prior to starting therapy.
- Acceptable liver function:
Bilirubin < 2.5 times institutional upper limit of normal (ULN)
aspartate aminotransferase (SGOT) and alanine aminotransferase (SGPT) < 2.5 times ULN

- Acceptable renal function:
Serum creatinine < 2.5 times ULN

- Acceptable hematologic status:
Absolute neutrophil count (ANC) ≥ 1500 cells/mm3 (1.5 ×109/L)
Platelet count ≥ 100,000 platelet/mm3 (100 ×109/L)
Hemoglobin ≥ 9 g/dL.
- At least 4 wks since prior radiation.
- Ability to understand and willingness to sign a written informed consent document.
- Patients on either treatment arm will be considered for crossover if they demonstrate evidence of radiographic disease progression.

Exclusion Criteria:

Pain due to metastatic prostate cancer requiring treatment intervention.
Eastern Cooperative Oncology Group Performance status ≥3
Prior treatment with enzalutamide is prohibited
Prior treatment with docetaxel or cabazitaxel for metastatic castration-resistant prostate cancer is prohibited.
Requires urinary catheterization for voiding due to obstruction secondary to prostatic enlargement well documented to be due to prostate cancer or benign prostatic hyperplasia (BPH).
Evidence of disease in sites or extent that, in the opinion of the investigator, would put the patient at risk from therapy with testosterone (e.g. femoral metastases with concern over fracture risk, severe and extensive spinal metastases with concern over spinal cord compression, extensive liver metastases)
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
Active uncontrolled infection, including known history of HIV/AIDS or hepatitis B or C.
Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule.
Patients receiving anticoagulation therapy with Coumadin are not eligible for study. [Patients on non-coumadin anticoagulants (Lovenox, Xarelto, etc.) are eligible for study. Patients on Coumadin who can be transitioned to lovenox prior to starting study treatments will be eligible].
Patients with prior history of a thromboembolic event within the last 12 months that is not being treated with systemic anticoagulation are excluded.
Patients allergic to sesame seed oil or cottonseed oil are excluded.
Major surgery (eg, requiring general anesthesia) within 3 weeks before screening, or has not fully recovered from prior surgery (ie, unhealed wound). Note: subjects with planned surgical procedures to be conducted under local anesthesia may participate.

Contacts/Locations Module

Name	Affiliation	Role
Samuel Denmeade, MD	Johns Hopkins School of Medicine - Sidney Kimmel Comprehensive Cancer Center	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Unversity of Alabama		Birmingham	Alabama	35294	United States
City of Hope

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
33617303	Derived	Denmeade SR, Wang H, Agarwal N, Smith DC, Schweizer MT, Stein MN, Assikis V, Twardowski PW, Flaig TW, Szmulewitz RZ, Holzbeierlein JM, Hauke RJ, Sonpavde G, Garcia JA, Hussain A, Sartor O, Mao S, Cao H, Fu W, Wang T, Abdallah R, Lim SJ, Bolejack V, Paller CJ, Carducci MA, Markowski MC, Eisenberger MA, Antonarakis ES. TRANSFORMER: A Randomized Phase II Study Comparing Bipolar Androgen Therapy Versus Enzalutamide in Asymptomatic Men With Castration-Resistant Metastatic Prostate Cancer. J Clin Oncol. 2021 Apr 20;39(12):1371-1382. doi: 10.1200/JCO.20.02759. Epub 2021 Feb 22.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Arm A: Testosterone Cypionate or Testosterone Enanthate	Patients on BAT will receive testosterone cypionate or testosterone enanthate administered as an intramuscular injection. A dose of 400 mg of either agent will be injected intramuscularly (IM) every 28 days. Testosterone cypionate: Depo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble of the androgenic hormone testosterone. Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. Depo-Testosterone Injection is available in two strengths, 100 mg/mL and 200 mg/mL testosterone cypionate. Testosterone Enanthate: Testosterone Enanthate Injection, for intramuscular injection, contains testosterone enanthate which is the oil-soluble ester of the androgenic hormone testosterone. Enanthate Injection is available as a colorless to pale yellow solution. Each mL contains 200 mg testosterone enanthate in sesame oil with 5 mg chlorobutanol as a preservative.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
SAP	No	Yes	No	Statistical Analysis Plan	Mar 27, 2017	Jan 9, 2019

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

No data available

No data is available for this block.

Intervention Browse Module

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Arm A: Testosterone Cypionate or Testosterone Enanthate	Patients on BAT will receive testosterone cypionate or testosterone enanthate administered as an intramuscular injection. A dose of 400 mg of either agent will be injected intramuscularly (IM) every 28 days. Testosterone cypionate: Depo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble of the androgenic hormone testosterone. Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. Depo-Testosterone Injection is available in two strengths, 100 mg/mL and 200 mg/mL testosterone cypionate. Testosterone Enanthate: Testosterone Enanthate Injection, for intramuscular injection, contains testosterone enanthate which is the oil-soluble ester of the androgenic hormone testosterone. Enanthate Injection is available as a colorless to pale yellow solution. Each mL contains 200 mg testosterone enanthate in sesame oil with 5 mg chlorobutanol as a preservative.
BG001	Arm B: Enzalutamide	Patients randomized to enzalutamide will be prescribed enzalutamide 40 mg tablets and instructed to take 4 tablets per day orally for 28 days/cycle. Enzalutamide: Enzalutamide is a white crystalline non-hygroscopic solid. It is practically insoluble in water. Enzalutamide is provided as liquid-filled soft gelatin capsules for oral administration. Each capsule contains 40 mg of enzalutamide as a solution in caprylocaproyl polyoxylglycerides. The inactive ingredients are caprylocaproyl polyoxylglycerides, butylated hydroxyanisole, butylated hydroxytoluene, gelatin, sorbitol sorbitan solution, glycerin, purified water, titanium dioxide, and black iron oxide.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG0005.62(4.76 to 5.91) OG0015.72(3.78 to 8.34)

Secondary

Radiographic Progression

Number of months until 20% increase in the sum of target lesions on CT scans.

Posted

Median

Full Range

months

up to 2 years

ID	Title	Description
OG000	Arm A: Testosterone Cypionate or Testosterone Enanthate	Patients on BAT will receive testosterone cypionate or testosterone enanthate administered as an intramuscular injection. A dose of 400 mg of either agent will be injected intramuscularly (IM) every 28 days. Testosterone cypionate: Depo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble of the androgenic hormone testosterone. Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. Depo-Testosterone Injection is available in two strengths, 100 mg/mL and 200 mg/mL testosterone cypionate. Testosterone Enanthate: Testosterone Enanthate Injection, for intramuscular injection, contains testosterone enanthate which is the oil-soluble ester of the androgenic hormone testosterone. Enanthate Injection is available as a colorless to pale yellow solution. Each mL contains 200 mg testosterone enanthate in sesame oil with 5 mg chlorobutanol as a preservative.
OG001	Arm B: Enzalutamide	Patients randomized to enzalutamide will be prescribed enzalutamide 40 mg tablets and instructed to take 4 tablets per day orally for 28 days/cycle. Enzalutamide: Enzalutamide is a white crystalline non-hygroscopic solid. It is practically insoluble in water. Enzalutamide is provided as liquid-filled soft gelatin capsules for oral administration. Each capsule contains 40 mg of enzalutamide as a solution in caprylocaproyl polyoxylglycerides. The inactive ingredients are caprylocaproyl polyoxylglycerides, butylated hydroxyanisole, butylated hydroxytoluene, gelatin, sorbitol sorbitan solution, glycerin, purified water, titanium dioxide, and black iron oxide.

Secondary

Prostate-Specific Antigen Response Rate

Number of participants achieving a Prostate-Specific Antigen decline ≥ 50% according to Prostate Cancer Working Group (PCWG2) criteria.

Data was not evaluable for this outcome measure in 7/94 participants from arm A and 7/101 participants from arm B.

Posted

Count of Participants

Participants

Up to 2 years

ID	Title	Description
OG000	Arm A: Testosterone Cypionate or Testosterone Enanthate	Patients on BAT will receive testosterone cypionate or testosterone enanthate administered as an intramuscular injection. A dose of 400 mg of either agent will be injected intramuscularly (IM) every 28 days. Testosterone cypionate: Depo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble of the androgenic hormone testosterone. Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. Depo-Testosterone Injection is available in two strengths, 100 mg/mL and 200 mg/mL testosterone cypionate. Testosterone Enanthate: Testosterone Enanthate Injection, for intramuscular injection, contains testosterone enanthate which is the oil-soluble ester of the androgenic hormone testosterone. Enanthate Injection is available as a colorless to pale yellow solution. Each mL contains 200 mg testosterone enanthate in sesame oil with 5 mg chlorobutanol as a preservative.
OG001	Arm B: Enzalutamide	Patients randomized to enzalutamide will be prescribed enzalutamide 40 mg tablets and instructed to take 4 tablets per day orally for 28 days/cycle. Enzalutamide: Enzalutamide is a white crystalline non-hygroscopic solid. It is practically insoluble in water. Enzalutamide is provided as liquid-filled soft gelatin capsules for oral administration. Each capsule contains 40 mg of enzalutamide as a solution in caprylocaproyl polyoxylglycerides. The inactive ingredients are caprylocaproyl polyoxylglycerides, butylated hydroxyanisole, butylated hydroxytoluene, gelatin, sorbitol sorbitan solution, glycerin, purified water, titanium dioxide, and black iron oxide.

Secondary

Objective Response Rate as Determined by RECIST

Number of participants with partial (PR) or complete response (CR) as defined by response evaluation criteria in solid tumors (RECIST), where CR is a disappearance of all target lesions and PR is ≥30% reduction in the sum of the longest diameter of target lesions.

Only participants with at least one post-baseline assessment were included to assess this outcome measure. Data was not evaluable in 61/94 participants from arm A and 77/101 participants from arm B.

Posted

Count of Participants

Participants

Up to 2 years

ID	Title	Description
OG000	Arm A: Testosterone Cypionate or Testosterone Enanthate	Patients on BAT will receive testosterone cypionate or testosterone enanthate administered as an intramuscular injection. A dose of 400 mg of either agent will be injected intramuscularly (IM) every 28 days. Testosterone cypionate: Depo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble of the androgenic hormone testosterone. Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. Depo-Testosterone Injection is available in two strengths, 100 mg/mL and 200 mg/mL testosterone cypionate. Testosterone Enanthate: Testosterone Enanthate Injection, for intramuscular injection, contains testosterone enanthate which is the oil-soluble ester of the androgenic hormone testosterone. Enanthate Injection is available as a colorless to pale yellow solution. Each mL contains 200 mg testosterone enanthate in sesame oil with 5 mg chlorobutanol as a preservative.

Secondary

Time to Prostate-Specific Antigen Progression

Reported as number of months till Prostate-Specific Antigen increase of greater or equal to 50% according to Prostate Cancer Working Group (PCWG2) criteria.

Date is not evaluable for this outcome measure in 3/94 participants from arm A and 3/101 participants from arm B.

Posted

Median

95% Confidence Interval

month

Up to 2 years

ID	Title	Description
OG000	Arm A: Testosterone Cypionate or Testosterone Enanthate	Patients on BAT will receive testosterone cypionate or testosterone enanthate administered as an intramuscular injection. A dose of 400 mg of either agent will be injected intramuscularly (IM) every 28 days. Testosterone cypionate: Depo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble of the androgenic hormone testosterone. Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. Depo-Testosterone Injection is available in two strengths, 100 mg/mL and 200 mg/mL testosterone cypionate. Testosterone Enanthate: Testosterone Enanthate Injection, for intramuscular injection, contains testosterone enanthate which is the oil-soluble ester of the androgenic hormone testosterone. Enanthate Injection is available as a colorless to pale yellow solution. Each mL contains 200 mg testosterone enanthate in sesame oil with 5 mg chlorobutanol as a preservative.
OG001	Arm B: Enzalutamide

Secondary

Quality of Life as Assessed by the Positive Affect Score of the Positive and Negative Affect Schedule (PANAS)

The Positive Affect Score is calculated by adding the scores on items 1, 3, 5, 9, 10, 12, 14, 16, 17, and 19. Scores can range from 10 - 50, with higher scores representing higher levels of positive affect.

Questionnaires were not completed by all participants. Therefore, data was only collected from: Arm A- 87/94 at baseline, 81/94 at month 1, 71/94 at month 3, 54/94 at month 6 and 17/94 at month 12. Arm B- 93/101 at baseline, 86/101 at month 1, 75/101 at month 3, 55/101 at month 6 and 25/101 at month 12.

Posted

Mean

Standard Deviation

score on a scale

up to 1 year

ID	Title	Description
OG000	Arm A: Testosterone Cypionate or Testosterone Enanthate	Patients on BAT will receive testosterone cypionate or testosterone enanthate administered as an intramuscular injection. A dose of 400 mg of either agent will be injected intramuscularly (IM) every 28 days. Testosterone cypionate: Depo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble of the androgenic hormone testosterone. Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. Depo-Testosterone Injection is available in two strengths, 100 mg/mL and 200 mg/mL testosterone cypionate. Testosterone Enanthate: Testosterone Enanthate Injection, for intramuscular injection, contains testosterone enanthate which is the oil-soluble ester of the androgenic hormone testosterone. Enanthate Injection is available as a colorless to pale yellow solution. Each mL contains 200 mg testosterone enanthate in sesame oil with 5 mg chlorobutanol as a preservative.

Secondary

Quality of Life as Assessed by the Negative Affect Score of the Positive and Negative Affect Schedule (PANAS)

The Negative Affect Score is calculated by adding the scores on items 2, 4, 6, 7, 8, 11, 13, 15, 18, and 20. Scores can range from 10 - 50, with lower scores representing lower levels of negative affect.

Questionnaires were not completed by all participants. Therefore, data was only collected from: Arm A- 87/94 at baseline, 81/94 at month 1, 71/94 at month 3, 54/94 at month 6 and 17/94 at month 12.Arm B- 93/101 at baseline, 86/101 at month 1, 75/101 at month 3, 55/101 at month 6 and 25/101 at month 12.

Posted

Mean

Standard Deviation

score on a scale

up to 1 year

ID	Title	Description
OG000	Arm A: Testosterone Cypionate or Testosterone Enanthate	Patients on BAT will receive testosterone cypionate or testosterone enanthate administered as an intramuscular injection. A dose of 400 mg of either agent will be injected intramuscularly (IM) every 28 days. Testosterone cypionate: Depo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble of the androgenic hormone testosterone. Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. Depo-Testosterone Injection is available in two strengths, 100 mg/mL and 200 mg/mL testosterone cypionate. Testosterone Enanthate: Testosterone Enanthate Injection, for intramuscular injection, contains testosterone enanthate which is the oil-soluble ester of the androgenic hormone testosterone. Enanthate Injection is available as a colorless to pale yellow solution. Each mL contains 200 mg testosterone enanthate in sesame oil with 5 mg chlorobutanol as a preservative.

Secondary

Change in Quality of Life as Assessed by the International Index of Erectile Function (IIEF) Questionnaire

The IIEF assesses erectile function (EF), orgasmic function (OF), sexual desire (SD), intercourse satisfaction (IS), orgasmic satisfaction (OS). Each of domains are scored on a scale of 0 to 5 with a lower score indicating a bad quality sex life. The IIEF questionnaire has a total score that ranges from 5 to 25 with lower score indicating less erectile dysfunction. A positive change in the score reflects better outcome.

Questionnaires were not completed by all participants. Therefore, data was only collected from: Arm A- 72/94 at baseline to month 1, 63/94 at month 3, 42/94 at month 6, and 14/94 at month 12. Arm B- 74/101 at month 1, 57/101 at month 3, 46/101 at month 6 and 20/101 at month 12.

Posted

Mean

Standard Deviation

score on a scale

up to 1 year

ID	Title	Description
OG000	Arm A: Testosterone Cypionate or Testosterone Enanthate	Patients on BAT will receive testosterone cypionate or testosterone enanthate administered as an intramuscular injection. A dose of 400 mg of either agent will be injected intramuscularly (IM) every 28 days. Testosterone cypionate: Depo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble of the androgenic hormone testosterone. Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. Depo-Testosterone Injection is available in two strengths, 100 mg/mL and 200 mg/mL testosterone cypionate. Testosterone Enanthate: Testosterone Enanthate Injection, for intramuscular injection, contains testosterone enanthate which is the oil-soluble ester of the androgenic hormone testosterone. Enanthate Injection is available as a colorless to pale yellow solution. Each mL contains 200 mg testosterone enanthate in sesame oil with 5 mg chlorobutanol as a preservative.

Secondary

Quality of Life as Assessed by Short Form 36

All questions are scored on a scale from 0 to 100. The total score from all of the questions answered is divided by the total number of the questions answered yielding a global score from 0-100 with 100 representing the highest level of functioning possible.

Questionnaires were not completed by all participants. Therefore, data was only collected from: Arm A- 89/94 at baseline, 84/94 at month 1, 74/94 at month 3, 55/94 at month 6 and 18/94 at month 12.Arm B- 96/101 at baseline, 86/101 at month 1, 81/101 at month 3, 56/101 at month 6 and 25/101 at month 12.

Posted

Mean

Standard Deviation

score on a scale

up to 1 year

ID	Title	Description
OG000	Arm A: Testosterone Cypionate or Testosterone Enanthate	Patients on BAT will receive testosterone cypionate or testosterone enanthate administered as an intramuscular injection. A dose of 400 mg of either agent will be injected intramuscularly (IM) every 28 days. Testosterone cypionate: Depo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble of the androgenic hormone testosterone. Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. Depo-Testosterone Injection is available in two strengths, 100 mg/mL and 200 mg/mL testosterone cypionate. Testosterone Enanthate: Testosterone Enanthate Injection, for intramuscular injection, contains testosterone enanthate which is the oil-soluble ester of the androgenic hormone testosterone. Enanthate Injection is available as a colorless to pale yellow solution. Each mL contains 200 mg testosterone enanthate in sesame oil with 5 mg chlorobutanol as a preservative.

Secondary

Quality of Life as Assessed by FACIT Fatigue Scale

The Functional Assessment of Chronic Illness Therapy - Fatigue has a score range of 0-52 with higher scores indicating better quality of life.

Questionnaires were not completed by all participants. Therefore, data was only collected from: 84/94 at month 1, 76/94 at month 3, 55/94 at month 6 and 18/94 at month 12.Arm B- 87/101 at month 1, 81/101 at month 3, 56/101 at month 6 and 25/101 at month 12

Posted

Mean

Standard Deviation

score on a scale

up to 1 year

ID	Title	Description
OG000	Arm A: Testosterone Cypionate or Testosterone Enanthate	Patients on BAT will receive testosterone cypionate or testosterone enanthate administered as an intramuscular injection. A dose of 400 mg of either agent will be injected intramuscularly (IM) every 28 days. Testosterone cypionate: Depo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble of the androgenic hormone testosterone. Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. Depo-Testosterone Injection is available in two strengths, 100 mg/mL and 200 mg/mL testosterone cypionate. Testosterone Enanthate: Testosterone Enanthate Injection, for intramuscular injection, contains testosterone enanthate which is the oil-soluble ester of the androgenic hormone testosterone. Enanthate Injection is available as a colorless to pale yellow solution. Each mL contains 200 mg testosterone enanthate in sesame oil with 5 mg chlorobutanol as a preservative.
OG001

Secondary

Pain Severity as Assessed by the Brief Pain Inventory

Severity is calculated by adding the scores for questions 2, 3, 4 and 5 and then dividing by 4. This gives a severity score out of 10, high score indicates more severe pain.

For Arm A, the data was only collected from 85/94 at baseline, 78/94 at month 1, 67/94 at month 3, 54/94 at month 6, 17/94 at month 12.

For Arm B, the data was only collected from 92/101 at baseline, 82/101 at month 1, 76/101 at month 3, 54/101 at month 6, 24/101 at month 12.

Posted

Mean

Standard Deviation

score on a scale

1 year

ID	Title	Description
OG000	Arm A: Testosterone Cypionate or Testosterone Enanthate	Patients on BAT will receive testosterone cypionate or testosterone enanthate administered as an intramuscular injection. A dose of 400 mg of either agent will be injected intramuscularly (IM) every 28 days. Testosterone cypionate: Depo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble of the androgenic hormone testosterone. Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. Depo-Testosterone Injection is available in two strengths, 100 mg/mL and 200 mg/mL testosterone cypionate. Testosterone Enanthate: Testosterone Enanthate Injection, for intramuscular injection, contains testosterone enanthate which is the oil-soluble ester of the androgenic hormone testosterone. Enanthate Injection is available as a colorless to pale yellow solution. Each mL contains 200 mg testosterone enanthate in sesame oil with 5 mg chlorobutanol as a preservative.

Secondary

Pain Interference as Assessed by the Brief Pain Inventory

Interference is calculated by adding the scores for questions 8a, b, c, d, e, f and g and then dividing by 7. This gives an interference score out of 10, higher score indicates more pain interference.

For Arm A, the data was only collected from 82/94 at baseline, 78/94 at month 1, 65/94 at month 3, 53/94 at month 6, 17/94 at month 12.

For Arm B, the data was only collected from 91/101 at baseline, 81/101 at month 1, 76/101 at month 3, 55/101 at month 6, 25/101 at month 12.

Posted

Mean

Standard Deviation

score on a scale

1 year

ID	Title	Description
OG000	Arm A: Testosterone Cypionate or Testosterone Enanthate	Patients on BAT will receive testosterone cypionate or testosterone enanthate administered as an intramuscular injection. A dose of 400 mg of either agent will be injected intramuscularly (IM) every 28 days. Testosterone cypionate: Depo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble of the androgenic hormone testosterone. Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. Depo-Testosterone Injection is available in two strengths, 100 mg/mL and 200 mg/mL testosterone cypionate. Testosterone Enanthate: Testosterone Enanthate Injection, for intramuscular injection, contains testosterone enanthate which is the oil-soluble ester of the androgenic hormone testosterone. Enanthate Injection is available as a colorless to pale yellow solution. Each mL contains 200 mg testosterone enanthate in sesame oil with 5 mg chlorobutanol as a preservative.

Secondary

Overall Survival

Time until death for any reasons

Posted

Median

95% Confidence Interval

months

up to 3 years

ID	Title	Description
OG000	Arm A: Testosterone Cypionate or Testosterone Enanthate	Patients on BAT will receive testosterone cypionate or testosterone enanthate administered as an intramuscular injection. A dose of 400 mg of either agent will be injected intramuscularly (IM) every 28 days. Testosterone cypionate: Depo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble of the androgenic hormone testosterone. Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. Depo-Testosterone Injection is available in two strengths, 100 mg/mL and 200 mg/mL testosterone cypionate. Testosterone Enanthate: Testosterone Enanthate Injection, for intramuscular injection, contains testosterone enanthate which is the oil-soluble ester of the androgenic hormone testosterone. Enanthate Injection is available as a colorless to pale yellow solution. Each mL contains 200 mg testosterone enanthate in sesame oil with 5 mg chlorobutanol as a preservative.
OG001	Arm B: Enzalutamide	Patients randomized to enzalutamide will be prescribed enzalutamide 40 mg tablets and instructed to take 4 tablets per day orally for 28 days/cycle. Enzalutamide: Enzalutamide is a white crystalline non-hygroscopic solid. It is practically insoluble in water. Enzalutamide is provided as liquid-filled soft gelatin capsules for oral administration. Each capsule contains 40 mg of enzalutamide as a solution in caprylocaproyl polyoxylglycerides. The inactive ingredients are caprylocaproyl polyoxylglycerides, butylated hydroxyanisole, butylated hydroxytoluene, gelatin, sorbitol sorbitan solution, glycerin, purified water, titanium dioxide, and black iron oxide.

Secondary

Progression Free Survival on Crossover Treatment

Time from initiation of therapy to progression on crossover treatment

Posted

Median

95% Confidence Interval

months

up to 2 years

ID	Title	Description
OG000	Arm A: Testosterone Cypionate or Testosterone Enanthate	Patients on BAT will receive testosterone cypionate or testosterone enanthate administered as an intramuscular injection. A dose of 400 mg of either agent will be injected intramuscularly (IM) every 28 days. Testosterone cypionate: Depo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble of the androgenic hormone testosterone. Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. Depo-Testosterone Injection is available in two strengths, 100 mg/mL and 200 mg/mL testosterone cypionate. Testosterone Enanthate: Testosterone Enanthate Injection, for intramuscular injection, contains testosterone enanthate which is the oil-soluble ester of the androgenic hormone testosterone. Enanthate Injection is available as a colorless to pale yellow solution. Each mL contains 200 mg testosterone enanthate in sesame oil with 5 mg chlorobutanol as a preservative.
OG001	Arm B: Enzalutamide	Patients randomized to enzalutamide will be prescribed enzalutamide 40 mg tablets and instructed to take 4 tablets per day orally for 28 days/cycle. Enzalutamide: Enzalutamide is a white crystalline non-hygroscopic solid. It is practically insoluble in water. Enzalutamide is provided as liquid-filled soft gelatin capsules for oral administration. Each capsule contains 40 mg of enzalutamide as a solution in caprylocaproyl polyoxylglycerides. The inactive ingredients are caprylocaproyl polyoxylglycerides, butylated hydroxyanisole, butylated hydroxytoluene, gelatin, sorbitol sorbitan solution, glycerin, purified water, titanium dioxide, and black iron oxide.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Arm A: Testosterone Cypionate or Testosterone Enanthate	Patients on BAT will receive testosterone cypionate or testosterone enanthate administered as an intramuscular injection. A dose of 400 mg of either agent will be injected intramuscularly (IM) every 28 days. Testosterone cypionate: Depo-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble of the androgenic hormone testosterone. Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. Depo-Testosterone Injection is available in two strengths, 100 mg/mL and 200 mg/mL testosterone cypionate. Testosterone Enanthate: Testosterone Enanthate Injection, for intramuscular injection, contains testosterone enanthate which is the oil-soluble ester of the androgenic hormone testosterone. Enanthate Injection is available as a colorless to pale yellow solution. Each mL contains 200 mg testosterone enanthate in sesame oil with 5 mg chlorobutanol as a preservative.	0	94	4	94	22	94
EG001	Arm B: Enzalutamide	Patients randomized to enzalutamide will be prescribed enzalutamide 40 mg tablets and instructed to take 4 tablets per day orally for 28 days/cycle. Enzalutamide: Enzalutamide is a white crystalline non-hygroscopic solid. It is practically insoluble in water. Enzalutamide is provided as liquid-filled soft gelatin capsules for oral administration. Each capsule contains 40 mg of enzalutamide as a solution in caprylocaproyl polyoxylglycerides. The inactive ingredients are caprylocaproyl polyoxylglycerides, butylated hydroxyanisole, butylated hydroxytoluene, gelatin, sorbitol sorbitan solution, glycerin, purified water, titanium dioxide, and black iron oxide.	1	101	11	101	29	101

Serious Adverse Events

Term	Organ System	Assessment Type	Notes	Statistical Information
Bone pain	Musculoskeletal and connective tissue disorders	Non-systematic Assessment		EG0001 events1 affected94 at risk EG0010 events0 affected101 at risk
Stroke	Nervous system disorders	Non-systematic Assessment		EG0001 events1 affected94 at risk EG0010 events0 affected101 at risk
Back pain	Musculoskeletal and connective tissue disorders	Non-systematic Assessment		EG0002 events2 affected94 at risk EG0016 events6 affected101 at risk
Seizure	Nervous system disorders	Non-systematic Assessment		EG0000 events0 affected94 at risk EG0011 events1 affected101 at risk
myocardial infarction	Cardiac disorders	Non-systematic Assessment	ST elevation myocardial infarction (cardiac cauterization with stent placement)	EG0000 events0 affected94 at risk EG0012 events1 affected101 at risk
Anemia	Blood and lymphatic system disorders	Non-systematic Assessment		EG0000 events0 affected94 at risk EG0011 events1 affected101 at risk
Urinary Tract Infection	Infections and infestations	Non-systematic Assessment		EG0000 events0 affected94 at risk EG0011 events1 affected101 at risk
Pneumonia	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment		EG0000 events0 affected94 at risk EG0011 events1 affected101 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Atrial fibrillation	Cardiac disorders	Non-systematic Assessment	EG0005 events5 affected94 at risk EG0016 events6 affected101 at risk
Ear and labyrinth disorders	Ear and labyrinth disorders	Non-systematic Assessment	EG0003 events3 affected94 at risk EG0016 events6 affected101 at risk
Back pain	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG0006 events6 affected94 at risk EG0018 events8 affected101 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG0002 events2 affected94 at risk EG0018 events8 affected101 at risk
fatigue	General disorders	Non-systematic Assessment	EG00011 events11 affected94 at risk EG0013 events3 affected101 at risk
pain	General disorders	Non-systematic Assessment	EG0004 events4 affected94 at risk EG0019 events9 affected101 at risk

ID	Term
C016131	testosterone 17 beta-cypionate
C540278	enzalutamide
C004648	testosterone enanthate

ParticipantsBG002193

Patients randomized to enzalutamide will be prescribed enzalutamide 40 mg tablets and instructed to take 4 tablets per day orally for 28 days/cycle.

Enzalutamide: Enzalutamide is a white crystalline non-hygroscopic solid. It is practically insoluble in water. Enzalutamide is provided as liquid-filled soft gelatin capsules for oral administration. Each capsule contains 40 mg of enzalutamide as a solution in caprylocaproyl polyoxylglycerides. The inactive ingredients are caprylocaproyl polyoxylglycerides, butylated hydroxyanisole, butylated hydroxytoluene, gelatin, sorbitol sorbitan solution, glycerin, purified water, titanium dioxide, and black iron oxide.