Restore: RE-sensitizing With Supraphysiologic Testosterone to Overcome REsistance (The RESTORE Study)

Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)
Overall Status
Completed
CT.gov ID
NCT02090114
Collaborator
National Cancer Institute (NCI) (NIH)
112
2
4
86.6
56
0.6

Study Details

Study Description

Brief Summary

Single-arm, single site, open label study of the effects of parenteral testosterone followed by enzalutamide, abiraterone or castration-only therapy in men with metastatic CRPC who previously progressed on one of these forms of therapy. The study will enroll four cohorts of patients: men with metastatic CRPC who have progressed on enzalutamide (Cohort A; n=30); men with metastatic CRPC who have progressed on abiraterone acetate (Cohort B; n=30); men with metastatic CRPC who have progressed on first line castration-only therapy (Cohort C; n=30); men with metastatic CRPC with inactivating somatic or germline mutations in ≥2 of the genes TP53, PTEN, or RB1 (Cohort D; n=20).

Condition or Disease Intervention/Treatment Phase
  • Drug: Testosterone cypionate
  • Drug: Testosterone Enanthate
  • Drug: Abiraterone acetate
  • Drug: Enzalutamide
Phase 2

Detailed Description

The trial will enroll up to 110 patients, 30 for each Cohorts A-C and 20 for Cohort D. Eligible patients will continue on androgen ablative therapy with LHRH agonist (i.e. Zoladex, Trelstar, Eligard or Lupron) if not surgically castrated to suppress endogenous testosterone production. Patients will also receive intramuscular injection with either testosterone cypionate or testosterone enanthate at a dose of 400 mg every 28 days. This dosing scheme was designed to produce rapidly fluctuating serum testosterone levels from the supraphysiologic to the near-castrate range (i.e. Bipolar Androgen Therapy [BAT]). Assessments for response to testosterone will be made approximately every 3 months. Upon displaying evidence of progression, patients will then go on to receive either abiraterone (Cohort B) or enzalutamide (Cohort A), whichever agent they had previously progressed on prior to study enrollment. Patients in Cohort C will remain on LHRH agonist therapy and receive no additional androgen ablative hormonal therapy while those in the mutation-positive Cohort D will receive enzalutamide regardless of prior therapy.

Study Design

Study Type:
Interventional
Actual Enrollment :
112 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Study to Determine Sequential Response to Bipolar Androgen Therapy (BAT) Followed by Enzalutamide or Abiraterone Post-BAT in Men With Prostate Cancer Progressing on Combined Androgen Ablative Therapies
Actual Study Start Date :
Aug 25, 2014
Actual Primary Completion Date :
Nov 11, 2021
Actual Study Completion Date :
Nov 11, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Cohort A:Post-enzalutamide

Men with castration-resistant prostate cancer who have progressed on enzalutamide will be enrolled to this cohort. These patients will then receive intramuscular injections with testosterone cypionate 400 mg every 28 days or testosterone enanthate 400 mg every 28 days. Upon progression on testosterone cypionate or enanthate, men will be retreated with enzalutamide 160 mg by mouth daily.

Drug: 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 and will be administered at 400mg IM every 28 days.
Other Names:
  • DEPO-Testosterone Injection
  • Drug: 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. Will be administered at 400mg IM every 28 days.
    Other Names:
  • Delatestryl
  • Drug: Enzalutamide
    XTANDI is provided as liquid-filled soft gelatin capsules for oral administration. Each capsule contains 40 mg of enzalutamide as a solution in caprylocaproyl polyoxylglycerides.
    Other Names:
  • Xtandi
  • Experimental: Cohort B: Post-abiraterone

    Men with castration-resistant prostate cancer who have progressed on abiraterone will be enrolled to this cohort. These patients will then receive intramuscular injections with testosterone cypionate 400 mg every 28 days or testosterone enanthate 400 mg every 28 days. Upon progression on testosterone cypionate or enanthate, men will be retreated with abiraterone 1000 mg by mouth daily.

    Drug: 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 and will be administered at 400mg IM every 28 days.
    Other Names:
  • DEPO-Testosterone Injection
  • Drug: 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. Will be administered at 400mg IM every 28 days.
    Other Names:
  • Delatestryl
  • Drug: Abiraterone acetate
    Abiraterone is an inhibitor of CYP17 (17α-hydroxylase/C17,20-lyase). Each ZYTIGA tablet contains 250 mg of abiraterone acetate.
    Other Names:
  • Zytiga
  • Experimental: Cohort C: Castration Only

    Men with metastatic prostate cancer who have only received first line hormone therapy with LHRH agonist alone or LHRH agonist plus an anti-androgen. Patients who have developed castrate resistance to first line therapy and have then received second line hormone therapy of any kind (including flutamide, bicalutamide, nilutamide, ketoconazole, abiraterone, enzalutamide, ARN-509 and investigational anti-androgens) are not eligible for enrollment in this cohort.

    Drug: 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 and will be administered at 400mg IM every 28 days.
    Other Names:
  • DEPO-Testosterone Injection
  • Drug: 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. Will be administered at 400mg IM every 28 days.
    Other Names:
  • Delatestryl
  • Experimental: Cohort D: Mutation

    Men with metastatic prostate cancer who have castrate resistant prostate cancer with inactivating somatic or germline mutations in the genes TP53, RB1 or PTEN identified using clinical grade sequencing of tumor tissue performed by qualified laboratory. Patients must have mutations in ≥2 of these genes to be eligible. Eligible patients must have progressed on first line hormone therapy with LHRH agonist alone and must have received at least one but not more than two second generation androgen ablative therapy (i.e. Abiraterone, Enzalutamide or Apalutamide).

    Drug: 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 and will be administered at 400mg IM every 28 days.
    Other Names:
  • DEPO-Testosterone Injection
  • Drug: 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. Will be administered at 400mg IM every 28 days.
    Other Names:
  • Delatestryl
  • Outcome Measures

    Primary Outcome Measures

    1. Prostate Specific Antigen (PSA) Response to Bipolar Androgen Therapy (BAT) [up to 18 months]

      Number of participants with ≥50% PSA reduction from pre-BAT baseline level

    2. PSA Response to Enzalutamide or Abiraterone Acetate Post Bipolar Androgen Therapy [up to 24 months]

      Number of participants with ≥50% PSA reduction after enzalutamide or abiraterone acetate post-BAT from baseline

    Secondary Outcome Measures

    1. PSA Progression on Enzalutamide or Abiraterone Acetate or Castrate Levels Post-BAT [up to 18 months]

      Time to PSA progression on enzalutamide or abiraterone acetate or return to castrate levels of testosterone post-BAT, defined as the time from the date of re-initiation of enzalutamide or abiraterone acetate or castration-only therapy to the date of the PSA measurement when it shows an increase by ≥25% above the nadir value that occurred following re-initiation of enzalutamide or abiraterone acetate or castration-only therapy and confirmed by a repeat PSA 4 weeks later (PCWG2).

    2. PSA Progression on BAT (Bipolar Androgen Therapy ) [up to 18 months]

      Time to PSA progression on BAT. Time to PSA progression on BAT is defined as the time from the date of initial dose of Testosterone to the date of the PSA measurement when it shows an ≥25% increase above the nadir value and confirmed by a repeat PSA 4 weeks later (PCWG2 criteria) during the treatment with BAT.

    3. Disease Response as Defined by RECIST 1.1 (Soft Tissue Lesions) and PCWG2 Criteria (Bone Lesions) [up to 18 months]

      Number of participants with complete or partial response post-BAT as defined by RECIST 1.1 (for soft tissue lesions) and PCWG2 criteria (for bone disease), or return to castration-only post-BAT.

    4. Initiation of Docetaxel Chemotherapy [up to 18 months]

      Time to initiation of docetaxel chemotherapy

    5. Quality of Life (QoL) as Assessed by FACIT-F Score [up to 18 months]

      Functional Assessment of Chronic Illness Therapy, Fatigue Subscale (FACIT-F) assesses Fatigue with a total score range of 0-52, with a higher score reflecting better QoL.

    6. Safety and Tolerability as Assessed by Number of Participants With Adverse Events [18 months]

      Number of participants who experience adverse events, as defined by NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0.

    7. Quality of Life (QoL) as Assessed by RANDSF-36 [up to 18 months]

      RAND 36-Item Short Form (RANDSF-36) assesses physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, general health perceptions, and perceived change in health with a total score range of 0-100. 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 a higher score reflecting a better QoL.

    8. Quality of Life (QoL) as Assessed by BPI [up to 18 months]

      Brief Pain Inventory (BPI) assesses the severity of pain and its impact on functioning with scales ranging from 0-10, with a higher score indicating a higher level of pain.

    9. Quality of Life (QoL) as Assessed by IIEF [up to 18 months]

      International Index of Erectile Function (IIEF-5) is a diagnostic tool for erectile dysfunction, with a total score range of 5-25, with the lowest score indicating a higher degree of dysfunction.

    10. Quality of Life (QoL) as Assessed by PANAS [up to 18 months]

      Positive and Negative Affect Schedule (PANAS) is a self-report measure that is made up of two mood scales, one measuring positive affect and the other measuring negative affect, with a total score range from 10-50 with a higher score on the positive scale indicating greater levels of positive affect and a lower score on the negative scale indicating less of a negative affect.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Performance status ≤2

    • Age ≥18 years

    • Histologically-confirmed adenocarcinoma of the prostate

    • Progressing on continuous androgen ablative therapy (either surgical castration or LHRH agonist).

    • Documented castrate level of serum testosterone (<50 ng/dl).

    • For Cohorts A and B, patients must have progressed on prior treatment with enzalutamide or abiraterone acetate + prednisone (by PSA criteria or radiographically).

    • For castration-only Cohort C, patients must have developed castrate resistant prostate cancer after progressing on first line hormone therapy with either surgical castration or LHRH agonist or LHRH agonist plus an anti-androgen.

    • For Cohort D patients must have inactivating somatic or germline mutations in ≥2 of the genes TP53, PTEN, RB1

    • Patients progressing on LHRH agonist plus an anti-androgen as first line therapy must be off anti-androgen for 4 weeks prior to first treatment with testosterone.

    • Patients with rising PSA on two successive measurements at least two weeks apart.

    • For Cohort A (enzalutamide) and Cohort B (abiraterone acetate):

    • Prior treatment with up to 2 additional second line hormone therapies, including ketoconazole is allowed.

    • Patients who have progressed on both enzalutamide and abiraterone acetate are eligible and post-BAT will be retreated with the last second line agent they had received (e.g. patient receiving abiraterone then enzalutamide would receive retreatment with enzalutamide post-BAT).

    • Patients must be withdrawn from enzalutamide or abiraterone acetate for ≥ 4 weeks and have documented PSA increase after the withdrawal period.

    • Patients receiving prednisone in conjunction with abiraterone acetate must be weaned off prednisone prior to starting BAT.

    • For Cohort C (castration-only):

    • Patients must continue on castrating therapy throughout BAT treatment.

    • No prior second line hormone treatment with flutamide, bicalutamide, nilutamide, enzalutamide, abiraterone, ketoconazole, ARN-509 or other investigational androgen ablative therapies is permitted for Cohort C.

    • For Cohort D (mutation cohort):

    • Patients must continue on castrating therapy throughout BAT treatment.

    • Treatment with first-generation hormonal therapy (i.e. flutamide, bicalutamide, nilutamide), is allowed

    • Patient must have received at least one and not more than two second generation hormone therapies (i.e. enzalutamide, abiraterone, apalutamide).

    • For Cohorts A-D, 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

    • For Cohort D, one line of prior chemotherapy with docetaxel or cabazitaxel for metastatic castrate resistant prostate cancer is allowed

    • Acceptable liver function:

    • Bilirubin < 2.5 times institutional upper limit of normal (ULN)

    • AST (SGOT) and ALT (SGPT) < 2.5 times ULN

    • Acceptable renal function:

    -- Serum creatinine < 2.5 times ULN, OR

    • 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 weeks since prior surgery with full recovery (no persistent toxicity ≥ Grade 1).

    • Ability to understand and willingness to sign a written informed consent document.

    Exclusion Criteria:
    • Pain due to metastatic prostate cancer requiring opioid analgesics.

    • 5 sites of visceral disease in lung or liver (nonspecific lung nodules ≤1 cm in diameter are permitted).

    • Prior treatment with docetaxel or cabazitaxel for metastatic castration-resistant prostate cancer is prohibited.

    • Prior treatment with one line of chemotherapy for metastatic castration-resistant prostate cancer is allowed for Cohort D

    • Requires urinary catheterization for voiding due to obstruction secondary to prostatic enlargement thought to be due to prostate cancer or benign prostatic hyperplasia

    • 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, spinal metastases with concern over spinal cord compression, lymph node disease with concern for ureteral obstruction).

    • 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 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.

    • Prior history of a thromboembolic event within the last two years and not currently on systemic anticoagulation.

    • Hematocrit >50%, untreated severe obstructive sleep apnea, uncontrolled or poorly controlled heart failure [per Endocrine Society Clinical Practice Guidelines (67)].

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Sibley Memorial Hospital Washington District of Columbia United States 20016
    2 The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore Maryland United States 21231

    Sponsors and Collaborators

    • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Samuel Denmeade, MD, Johns Hopkins School of Medicine - Sidney Kimmel Comprehensive Cancer Center

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    ClinicalTrials.gov Identifier:
    NCT02090114
    Other Study ID Numbers:
    • J1416
    • NA_00093344
    • 1R01CA184012-01
    First Posted:
    Mar 18, 2014
    Last Update Posted:
    Jun 27, 2022
    Last Verified:
    Jun 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail 16 patients failed screen.
    Arm/Group Title Cohort A:Post-enzalutamide Cohort B: Post-abiraterone Cohort C: Castration Only Cohort D: Mutation
    Arm/Group Description Men with castration-resistant prostate cancer who have progressed on enzalutamide will be enrolled to this cohort. These patients will then receive intramuscular injections with testosterone cypionate 400 mg every 28 days or testosterone enanthate 400 mg every 28 days. Upon progression on testosterone cypionate or enanthate, men will be retreated with enzalutamide 160 mg by mouth daily. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Enzalutamide: XTANDI is provided as liquid-filled soft gelatin capsules for oral administration. Each capsule contains 40 mg of enzalutamide as a solution in caprylocaproyl polyoxylglycerides. Men with castration-resistant prostate cancer who have progressed on abiraterone will be enrolled to this cohort. These patients will then receive intramuscular injections with testosterone cypionate 400 mg every 28 days or testosterone enanthate 400 mg every 28 days. Upon progression on testosterone cypionate or enanthate, men will be retreated with abiraterone 1000 mg by mouth daily. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Abiraterone acetate: Abiraterone is an inhibitor of CYP17 (17α-hydroxylase/C17,20-lyase). Each ZYTIGA tablet contains 250 mg of abiraterone acetate. Men with metastatic prostate cancer who have only received first line hormone therapy with LHRH agonist alone or LHRH agonist plus an anti-androgen. Patients who have developed castrate resistance to first line therapy and have then received second line hormone therapy of any kind (including flutamide, bicalutamide, nilutamide, ketoconazole, abiraterone, enzalutamide, ARN-509 and investigational anti-androgens) are not eligible for enrollment in this cohort. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Men with metastatic prostate cancer who have castrate resistant prostate cancer with inactivating somatic or germline mutations in the genes TP53, RB1 or PTEN identified using clinical grade sequencing of tumor tissue performed by qualified laboratory. Patients must have mutations in ≥2 of these genes to be eligible. Eligible patients must have progressed on first line hormone therapy with LHRH agonist alone and must have received at least one but not more than two second generation androgen ablative therapy (i.e. Abiraterone, Enzalutamide or Apalutamide). 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days.
    Period Title: Overall Study
    STARTED 30 29 29 8
    COMPLETED 0 0 0 0
    NOT COMPLETED 30 29 29 8

    Baseline Characteristics

    Arm/Group Title Cohort A:Post-enzalutamide Cohort B: Post-abiraterone Cohort C: Castration Only Cohort D: Mutation Total
    Arm/Group Description Men with castration-resistant prostate cancer who have progressed on enzalutamide will be enrolled to this cohort. These patients will then receive intramuscular injections with testosterone cypionate 400 mg every 28 days or testosterone enanthate 400 mg every 28 days. Upon progression on testosterone cypionate or enanthate, men will be retreated with enzalutamide 160 mg by mouth daily. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Enzalutamide: XTANDI is provided as liquid-filled soft gelatin capsules for oral administration. Each capsule contains 40 mg of enzalutamide as a solution in caprylocaproyl polyoxylglycerides. Men with castration-resistant prostate cancer who have progressed on abiraterone will be enrolled to this cohort. These patients will then receive intramuscular injections with testosterone cypionate 400 mg every 28 days or testosterone enanthate 400 mg every 28 days. Upon progression on testosterone cypionate or enanthate, men will be retreated with abiraterone 1000 mg by mouth daily. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Abiraterone acetate: Abiraterone is an inhibitor of CYP17 (17α-hydroxylase/C17,20-lyase). Each ZYTIGA tablet contains 250 mg of abiraterone acetate. Men with metastatic prostate cancer who have only received first line hormone therapy with LHRH agonist alone or LHRH agonist plus an anti-androgen. Patients who have developed castrate resistance to first line therapy and have then received second line hormone therapy of any kind (including flutamide, bicalutamide, nilutamide, ketoconazole, abiraterone, enzalutamide, ARN-509 and investigational anti-androgens) are not eligible for enrollment in this cohort. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Men with metastatic prostate cancer who have castrate resistant prostate cancer with inactivating somatic or germline mutations in the genes TP53, RB1 or PTEN identified using clinical grade sequencing of tumor tissue performed by qualified laboratory. Patients must have mutations in ≥2 of these genes to be eligible. Eligible patients must have progressed on first line hormone therapy with LHRH agonist alone and must have received at least one but not more than two second generation androgen ablative therapy (i.e. Abiraterone, Enzalutamide or Apalutamide). 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Total of all reporting groups
    Overall Participants 30 29 29 8 96
    Age (Years) [Median (Full Range) ]
    Median (Full Range) [Years]
    74
    71
    69
    73
    72
    Sex: Female, Male (Count of Participants)
    Female
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Male
    30
    100%
    29
    100%
    29
    100%
    8
    100%
    96
    100%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    1
    3.4%
    1
    12.5%
    2
    2.1%
    Not Hispanic or Latino
    24
    80%
    26
    89.7%
    24
    82.8%
    7
    87.5%
    81
    84.4%
    Unknown or Not Reported
    6
    20%
    3
    10.3%
    4
    13.8%
    0
    0%
    13
    13.5%
    Race/Ethnicity, Customized (Count of Participants)
    White
    27
    90%
    26
    89.7%
    23
    79.3%
    7
    87.5%
    83
    86.5%
    Non-white
    3
    10%
    3
    10.3%
    6
    20.7%
    1
    12.5%
    13
    13.5%
    Region of Enrollment (Count of Participants)
    United States
    30
    100%
    29
    100%
    29
    100%
    8
    100%
    96
    100%

    Outcome Measures

    1. Primary Outcome
    Title Prostate Specific Antigen (PSA) Response to Bipolar Androgen Therapy (BAT)
    Description Number of participants with ≥50% PSA reduction from pre-BAT baseline level
    Time Frame up to 18 months

    Outcome Measure Data

    Analysis Population Description
    Only 7/8 patients were evaluable from Cohort D.
    Arm/Group Title Cohort A:Post-enzalutamide Cohort B: Post-abiraterone Cohort C: Castration Only Cohort D: Mutation
    Arm/Group Description Men with castration-resistant prostate cancer who have progressed on enzalutamide will be enrolled to this cohort. These patients will then receive intramuscular injections with testosterone cypionate 400 mg every 28 days or testosterone enanthate 400 mg every 28 days. Upon progression on testosterone cypionate or enanthate, men will be retreated with enzalutamide 160 mg by mouth daily. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Enzalutamide: XTANDI is provided as liquid-filled soft gelatin capsules for oral administration. Each capsule contains 40 mg of enzalutamide as a solution in caprylocaproyl polyoxylglycerides. Men with castration-resistant prostate cancer who have progressed on abiraterone will be enrolled to this cohort. These patients will then receive intramuscular injections with testosterone cypionate 400 mg every 28 days or testosterone enanthate 400 mg every 28 days. Upon progression on testosterone cypionate or enanthate, men will be retreated with abiraterone 1000 mg by mouth daily. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Abiraterone acetate: Abiraterone is an inhibitor of CYP17 (17α-hydroxylase/C17,20-lyase). Each ZYTIGA tablet contains 250 mg of abiraterone acetate. Men with metastatic prostate cancer who have only received first line hormone therapy with LHRH agonist alone or LHRH agonist plus an anti-androgen. Patients who have developed castrate resistance to first line therapy and have then received second line hormone therapy of any kind (including flutamide, bicalutamide, nilutamide, ketoconazole, abiraterone, enzalutamide, ARN-509 and investigational anti-androgens) are not eligible for enrollment in this cohort. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Men with metastatic prostate cancer who have castrate resistant prostate cancer with inactivating somatic or germline mutations in the genes TP53, RB1 or PTEN identified using clinical grade sequencing of tumor tissue performed by qualified laboratory. Patients must have mutations in ≥2 of these genes to be eligible. Eligible patients must have progressed on first line hormone therapy with LHRH agonist alone and must have received at least one but not more than two second generation androgen ablative therapy (i.e. Abiraterone, Enzalutamide or Apalutamide). 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days.
    Measure Participants 30 29 29 7
    Count of Participants [Participants]
    9
    30%
    5
    17.2%
    4
    13.8%
    2
    25%
    2. Primary Outcome
    Title PSA Response to Enzalutamide or Abiraterone Acetate Post Bipolar Androgen Therapy
    Description Number of participants with ≥50% PSA reduction after enzalutamide or abiraterone acetate post-BAT from baseline
    Time Frame up to 24 months

    Outcome Measure Data

    Analysis Population Description
    This outcome measure only applies to cohort A,B, and D. Only 22/30 (Cohort A), 19/29 (Cohort B) and 7/8 (Cohort D) patients had evaluable data.
    Arm/Group Title Cohort A:Post-enzalutamide Cohort B: Post-abiraterone Cohort C: Castration Only Cohort D: Mutation
    Arm/Group Description Men with castration-resistant prostate cancer who have progressed on enzalutamide will be enrolled to this cohort. These patients will then receive intramuscular injections with testosterone cypionate 400 mg every 28 days or testosterone enanthate 400 mg every 28 days. Upon progression on testosterone cypionate or enanthate, men will be retreated with enzalutamide 160 mg by mouth daily. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Enzalutamide: XTANDI is provided as liquid-filled soft gelatin capsules for oral administration. Each capsule contains 40 mg of enzalutamide as a solution in caprylocaproyl polyoxylglycerides. Men with castration-resistant prostate cancer who have progressed on abiraterone will be enrolled to this cohort. These patients will then receive intramuscular injections with testosterone cypionate 400 mg every 28 days or testosterone enanthate 400 mg every 28 days. Upon progression on testosterone cypionate or enanthate, men will be retreated with abiraterone 1000 mg by mouth daily. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Abiraterone acetate: Abiraterone is an inhibitor of CYP17 (17α-hydroxylase/C17,20-lyase). Each ZYTIGA tablet contains 250 mg of abiraterone acetate. Men with metastatic prostate cancer who have only received first line hormone therapy with LHRH agonist alone or LHRH agonist plus an anti-androgen. Patients who have developed castrate resistance to first line therapy and have then received second line hormone therapy of any kind (including flutamide, bicalutamide, nilutamide, ketoconazole, abiraterone, enzalutamide, ARN-509 and investigational anti-androgens) are not eligible for enrollment in this cohort. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Men with metastatic prostate cancer who have castrate resistant prostate cancer with inactivating somatic or germline mutations in the genes TP53, RB1 or PTEN identified using clinical grade sequencing of tumor tissue performed by qualified laboratory. Patients must have mutations in ≥2 of these genes to be eligible. Eligible patients must have progressed on first line hormone therapy with LHRH agonist alone and must have received at least one but not more than two second generation androgen ablative therapy (i.e. Abiraterone, Enzalutamide or Apalutamide). 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days.
    Measure Participants 22 19 0 7
    Count of Participants [Participants]
    15
    50%
    3
    10.3%
    2
    6.9%
    3. Secondary Outcome
    Title PSA Progression on Enzalutamide or Abiraterone Acetate or Castrate Levels Post-BAT
    Description Time to PSA progression on enzalutamide or abiraterone acetate or return to castrate levels of testosterone post-BAT, defined as the time from the date of re-initiation of enzalutamide or abiraterone acetate or castration-only therapy to the date of the PSA measurement when it shows an increase by ≥25% above the nadir value that occurred following re-initiation of enzalutamide or abiraterone acetate or castration-only therapy and confirmed by a repeat PSA 4 weeks later (PCWG2).
    Time Frame up to 18 months

    Outcome Measure Data

    Analysis Population Description
    Only 21/30 participants were evaluable from Cohort A. Only 19/29 participants were evaluable from Cohort B.This outcome measure does not apply to Cohort D.
    Arm/Group Title Cohort A:Post-enzalutamide Cohort B: Post-abiraterone Cohort C: Castration Only Cohort D: Mutation
    Arm/Group Description Men with castration-resistant prostate cancer who have progressed on enzalutamide will be enrolled to this cohort. These patients will then receive intramuscular injections with testosterone cypionate 400 mg every 28 days or testosterone enanthate 400 mg every 28 days. Upon progression on testosterone cypionate or enanthate, men will be retreated with enzalutamide 160 mg by mouth daily. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Enzalutamide: XTANDI is provided as liquid-filled soft gelatin capsules for oral administration. Each capsule contains 40 mg of enzalutamide as a solution in caprylocaproyl polyoxylglycerides. Men with castration-resistant prostate cancer who have progressed on abiraterone will be enrolled to this cohort. These patients will then receive intramuscular injections with testosterone cypionate 400 mg every 28 days or testosterone enanthate 400 mg every 28 days. Upon progression on testosterone cypionate or enanthate, men will be retreated with abiraterone 1000 mg by mouth daily. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Abiraterone acetate: Abiraterone is an inhibitor of CYP17 (17α-hydroxylase/C17,20-lyase). Each ZYTIGA tablet contains 250 mg of abiraterone acetate. Men with metastatic prostate cancer who have only received first line hormone therapy with LHRH agonist alone or LHRH agonist plus an anti-androgen. Patients who have developed castrate resistance to first line therapy and have then received second line hormone therapy of any kind (including flutamide, bicalutamide, nilutamide, ketoconazole, abiraterone, enzalutamide, ARN-509 and investigational anti-androgens) are not eligible for enrollment in this cohort. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Men with metastatic prostate cancer who have castrate resistant prostate cancer with inactivating somatic or germline mutations in the genes TP53, RB1 or PTEN identified using clinical grade sequencing of tumor tissue performed by qualified laboratory. Patients must have mutations in ≥2 of these genes to be eligible. Eligible patients must have progressed on first line hormone therapy with LHRH agonist alone and must have received at least one but not more than two second generation androgen ablative therapy (i.e. Abiraterone, Enzalutamide or Apalutamide). 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days.
    Measure Participants 21 19 29 0
    Median (95% Confidence Interval) [months]
    5.5
    3.7
    NA
    4. Secondary Outcome
    Title PSA Progression on BAT (Bipolar Androgen Therapy )
    Description Time to PSA progression on BAT. Time to PSA progression on BAT is defined as the time from the date of initial dose of Testosterone to the date of the PSA measurement when it shows an ≥25% increase above the nadir value and confirmed by a repeat PSA 4 weeks later (PCWG2 criteria) during the treatment with BAT.
    Time Frame up to 18 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Cohort A:Post-enzalutamide Cohort B: Post-abiraterone Cohort C: Castration Only Cohort D: Mutation
    Arm/Group Description Men with castration-resistant prostate cancer who have progressed on enzalutamide will be enrolled to this cohort. These patients will then receive intramuscular injections with testosterone cypionate 400 mg every 28 days or testosterone enanthate 400 mg every 28 days. Upon progression on testosterone cypionate or enanthate, men will be retreated with enzalutamide 160 mg by mouth daily. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Enzalutamide: XTANDI is provided as liquid-filled soft gelatin capsules for oral administration. Each capsule contains 40 mg of enzalutamide as a solution in caprylocaproyl polyoxylglycerides. Men with castration-resistant prostate cancer who have progressed on abiraterone will be enrolled to this cohort. These patients will then receive intramuscular injections with testosterone cypionate 400 mg every 28 days or testosterone enanthate 400 mg every 28 days. Upon progression on testosterone cypionate or enanthate, men will be retreated with abiraterone 1000 mg by mouth daily. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Abiraterone acetate: Abiraterone is an inhibitor of CYP17 (17α-hydroxylase/C17,20-lyase). Each ZYTIGA tablet contains 250 mg of abiraterone acetate. Men with metastatic prostate cancer who have only received first line hormone therapy with LHRH agonist alone or LHRH agonist plus an anti-androgen. Patients who have developed castrate resistance to first line therapy and have then received second line hormone therapy of any kind (including flutamide, bicalutamide, nilutamide, ketoconazole, abiraterone, enzalutamide, ARN-509 and investigational anti-androgens) are not eligible for enrollment in this cohort. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Men with metastatic prostate cancer who have castrate resistant prostate cancer with inactivating somatic or germline mutations in the genes TP53, RB1 or PTEN identified using clinical grade sequencing of tumor tissue performed by qualified laboratory. Patients must have mutations in ≥2 of these genes to be eligible. Eligible patients must have progressed on first line hormone therapy with LHRH agonist alone and must have received at least one but not more than two second generation androgen ablative therapy (i.e. Abiraterone, Enzalutamide or Apalutamide). 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days.
    Measure Participants 30 29 29 7
    Median (95% Confidence Interval) [months]
    3.3
    3.2
    0.93
    3
    5. Secondary Outcome
    Title Disease Response as Defined by RECIST 1.1 (Soft Tissue Lesions) and PCWG2 Criteria (Bone Lesions)
    Description Number of participants with complete or partial response post-BAT as defined by RECIST 1.1 (for soft tissue lesions) and PCWG2 criteria (for bone disease), or return to castration-only post-BAT.
    Time Frame up to 18 months

    Outcome Measure Data

    Analysis Population Description
    12/30 participants from Cohort A, 7/29 participants from Cohort B, 13/20 from Cohort C, and 7/8 participants from Cohort D were evaluable for this outcome measure.
    Arm/Group Title Cohort A:Post-enzalutamide Cohort B: Post-abiraterone Cohort C: Castration Only Cohort D: Mutation
    Arm/Group Description Men with castration-resistant prostate cancer who have progressed on enzalutamide will be enrolled to this cohort. These patients will then receive intramuscular injections with testosterone cypionate 400 mg every 28 days or testosterone enanthate 400 mg every 28 days. Upon progression on testosterone cypionate or enanthate, men will be retreated with enzalutamide 160 mg by mouth daily. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Enzalutamide: XTANDI is provided as liquid-filled soft gelatin capsules for oral administration. Each capsule contains 40 mg of enzalutamide as a solution in caprylocaproyl polyoxylglycerides. Men with castration-resistant prostate cancer who have progressed on abiraterone will be enrolled to this cohort. These patients will then receive intramuscular injections with testosterone cypionate 400 mg every 28 days or testosterone enanthate 400 mg every 28 days. Upon progression on testosterone cypionate or enanthate, men will be retreated with abiraterone 1000 mg by mouth daily. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Abiraterone acetate: Abiraterone is an inhibitor of CYP17 (17α-hydroxylase/C17,20-lyase). Each ZYTIGA tablet contains 250 mg of abiraterone acetate. Men with metastatic prostate cancer who have only received first line hormone therapy with LHRH agonist alone or LHRH agonist plus an anti-androgen. Patients who have developed castrate resistance to first line therapy and have then received second line hormone therapy of any kind (including flutamide, bicalutamide, nilutamide, ketoconazole, abiraterone, enzalutamide, ARN-509 and investigational anti-androgens) are not eligible for enrollment in this cohort. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Men with metastatic prostate cancer who have castrate resistant prostate cancer with inactivating somatic or germline mutations in the genes TP53, RB1 or PTEN identified using clinical grade sequencing of tumor tissue performed by qualified laboratory. Patients must have mutations in ≥2 of these genes to be eligible. Eligible patients must have progressed on first line hormone therapy with LHRH agonist alone and must have received at least one but not more than two second generation androgen ablative therapy (i.e. Abiraterone, Enzalutamide or Apalutamide). 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days.
    Measure Participants 12 7 13 7
    Count of Participants [Participants]
    6
    20%
    2
    6.9%
    4
    13.8%
    0
    0%
    6. Secondary Outcome
    Title Initiation of Docetaxel Chemotherapy
    Description Time to initiation of docetaxel chemotherapy
    Time Frame up to 18 months

    Outcome Measure Data

    Analysis Population Description
    Data was not collected to assess this outcome measure.
    Arm/Group Title Cohort A:Post-enzalutamide Cohort B: Post-abiraterone Cohort C: Castration Only Cohort D: Mutation
    Arm/Group Description Men with castration-resistant prostate cancer who have progressed on enzalutamide will be enrolled to this cohort. These patients will then receive intramuscular injections with testosterone cypionate 400 mg every 28 days or testosterone enanthate 400 mg every 28 days. Upon progression on testosterone cypionate or enanthate, men will be retreated with enzalutamide 160 mg by mouth daily. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Enzalutamide: XTANDI is provided as liquid-filled soft gelatin capsules for oral administration. Each capsule contains 40 mg of enzalutamide as a solution in caprylocaproyl polyoxylglycerides. Men with castration-resistant prostate cancer who have progressed on abiraterone will be enrolled to this cohort. These patients will then receive intramuscular injections with testosterone cypionate 400 mg every 28 days or testosterone enanthate 400 mg every 28 days. Upon progression on testosterone cypionate or enanthate, men will be retreated with abiraterone 1000 mg by mouth daily. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Abiraterone acetate: Abiraterone is an inhibitor of CYP17 (17α-hydroxylase/C17,20-lyase). Each ZYTIGA tablet contains 250 mg of abiraterone acetate. Men with metastatic prostate cancer who have only received first line hormone therapy with LHRH agonist alone or LHRH agonist plus an anti-androgen. Patients who have developed castrate resistance to first line therapy and have then received second line hormone therapy of any kind (including flutamide, bicalutamide, nilutamide, ketoconazole, abiraterone, enzalutamide, ARN-509 and investigational anti-androgens) are not eligible for enrollment in this cohort. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Men with metastatic prostate cancer who have castrate resistant prostate cancer with inactivating somatic or germline mutations in the genes TP53, RB1 or PTEN identified using clinical grade sequencing of tumor tissue performed by qualified laboratory. Patients must have mutations in ≥2 of these genes to be eligible. Eligible patients must have progressed on first line hormone therapy with LHRH agonist alone and must have received at least one but not more than two second generation androgen ablative therapy (i.e. Abiraterone, Enzalutamide or Apalutamide). 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days.
    Measure Participants 0 0 0 0
    7. Secondary Outcome
    Title Quality of Life (QoL) as Assessed by FACIT-F Score
    Description Functional Assessment of Chronic Illness Therapy, Fatigue Subscale (FACIT-F) assesses Fatigue with a total score range of 0-52, with a higher score reflecting better QoL.
    Time Frame up to 18 months

    Outcome Measure Data

    Analysis Population Description
    25/30 participants in Cohort A, 22/29 participants in Cohort B, 28/29 participants in Cohort C were evaluable for this outcome measure. Data was not collected from participants for Cohort D.
    Arm/Group Title Cohort A:Post-enzalutamide Cohort B: Post-abiraterone Cohort C: Castration Only Cohort D: Mutation
    Arm/Group Description Men with castration-resistant prostate cancer who have progressed on enzalutamide will be enrolled to this cohort. These patients will then receive intramuscular injections with testosterone cypionate 400 mg every 28 days or testosterone enanthate 400 mg every 28 days. Upon progression on testosterone cypionate or enanthate, men will be retreated with enzalutamide 160 mg by mouth daily. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Enzalutamide: XTANDI is provided as liquid-filled soft gelatin capsules for oral administration. Each capsule contains 40 mg of enzalutamide as a solution in caprylocaproyl polyoxylglycerides. Men with castration-resistant prostate cancer who have progressed on abiraterone will be enrolled to this cohort. These patients will then receive intramuscular injections with testosterone cypionate 400 mg every 28 days or testosterone enanthate 400 mg every 28 days. Upon progression on testosterone cypionate or enanthate, men will be retreated with abiraterone 1000 mg by mouth daily. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Abiraterone acetate: Abiraterone is an inhibitor of CYP17 (17α-hydroxylase/C17,20-lyase). Each ZYTIGA tablet contains 250 mg of abiraterone acetate. Men with metastatic prostate cancer who have only received first line hormone therapy with LHRH agonist alone or LHRH agonist plus an anti-androgen. Patients who have developed castrate resistance to first line therapy and have then received second line hormone therapy of any kind (including flutamide, bicalutamide, nilutamide, ketoconazole, abiraterone, enzalutamide, ARN-509 and investigational anti-androgens) are not eligible for enrollment in this cohort. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Men with metastatic prostate cancer who have castrate resistant prostate cancer with inactivating somatic or germline mutations in the genes TP53, RB1 or PTEN identified using clinical grade sequencing of tumor tissue performed by qualified laboratory. Patients must have mutations in ≥2 of these genes to be eligible. Eligible patients must have progressed on first line hormone therapy with LHRH agonist alone and must have received at least one but not more than two second generation androgen ablative therapy (i.e. Abiraterone, Enzalutamide or Apalutamide). 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days.
    Measure Participants 25 29 29 0
    Baseline
    13.28
    (6.73)
    16.86
    (7.62)
    13
    (5.57)
    Cycle 1 Day 85
    10.64
    (5.51)
    13.85
    (7.42)
    11.55
    (3.39)
    8. Secondary Outcome
    Title Safety and Tolerability as Assessed by Number of Participants With Adverse Events
    Description Number of participants who experience adverse events, as defined by NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
    Time Frame 18 months

    Outcome Measure Data

    Analysis Population Description
    In cohort D, data was only collected from 7/8 participants.
    Arm/Group Title Cohort A:Post-enzalutamide Cohort B: Post-abiraterone Cohort C: Castration Only Cohort D: Mutation
    Arm/Group Description Men with castration-resistant prostate cancer who have progressed on enzalutamide will be enrolled to this cohort. These patients will then receive intramuscular injections with testosterone cypionate 400 mg every 28 days or testosterone enanthate 400 mg every 28 days. Upon progression on testosterone cypionate or enanthate, men will be retreated with enzalutamide 160 mg by mouth daily. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Enzalutamide: XTANDI is provided as liquid-filled soft gelatin capsules for oral administration. Each capsule contains 40 mg of enzalutamide as a solution in caprylocaproyl polyoxylglycerides. Men with castration-resistant prostate cancer who have progressed on abiraterone will be enrolled to this cohort. These patients will then receive intramuscular injections with testosterone cypionate 400 mg every 28 days or testosterone enanthate 400 mg every 28 days. Upon progression on testosterone cypionate or enanthate, men will be retreated with abiraterone 1000 mg by mouth daily. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Abiraterone acetate: Abiraterone is an inhibitor of CYP17 (17α-hydroxylase/C17,20-lyase). Each ZYTIGA tablet contains 250 mg of abiraterone acetate. Men with metastatic prostate cancer who have only received first line hormone therapy with LHRH agonist alone or LHRH agonist plus an anti-androgen. Patients who have developed castrate resistance to first line therapy and have then received second line hormone therapy of any kind (including flutamide, bicalutamide, nilutamide, ketoconazole, abiraterone, enzalutamide, ARN-509 and investigational anti-androgens) are not eligible for enrollment in this cohort. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Men with metastatic prostate cancer who have castrate resistant prostate cancer with inactivating somatic or germline mutations in the genes TP53, RB1 or PTEN identified using clinical grade sequencing of tumor tissue performed by qualified laboratory. Patients must have mutations in ≥2 of these genes to be eligible. Eligible patients must have progressed on first line hormone therapy with LHRH agonist alone and must have received at least one but not more than two second generation androgen ablative therapy (i.e. Abiraterone, Enzalutamide or Apalutamide). 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days.
    Measure Participants 30 29 29 7
    Count of Participants [Participants]
    30
    100%
    29
    100%
    29
    100%
    7
    87.5%
    9. Secondary Outcome
    Title Quality of Life (QoL) as Assessed by RANDSF-36
    Description RAND 36-Item Short Form (RANDSF-36) assesses physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, general health perceptions, and perceived change in health with a total score range of 0-100. 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 a higher score reflecting a better QoL.
    Time Frame up to 18 months

    Outcome Measure Data

    Analysis Population Description
    25/30 participants in Cohort A, 19/29 participants in Cohort B, 25/29 participants in Cohort C were evaluable for this outcome measure. Data was not collected from participants in Cohort D.
    Arm/Group Title Cohort A:Post-enzalutamide Cohort B: Post-abiraterone Cohort C: Castration Only Cohort D: Mutation
    Arm/Group Description Men with castration-resistant prostate cancer who have progressed on enzalutamide will be enrolled to this cohort. These patients will then receive intramuscular injections with testosterone cypionate 400 mg every 28 days or testosterone enanthate 400 mg every 28 days. Upon progression on testosterone cypionate or enanthate, men will be retreated with enzalutamide 160 mg by mouth daily. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Enzalutamide: XTANDI is provided as liquid-filled soft gelatin capsules for oral administration. Each capsule contains 40 mg of enzalutamide as a solution in caprylocaproyl polyoxylglycerides. Men with castration-resistant prostate cancer who have progressed on abiraterone will be enrolled to this cohort. These patients will then receive intramuscular injections with testosterone cypionate 400 mg every 28 days or testosterone enanthate 400 mg every 28 days. Upon progression on testosterone cypionate or enanthate, men will be retreated with abiraterone 1000 mg by mouth daily. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Abiraterone acetate: Abiraterone is an inhibitor of CYP17 (17α-hydroxylase/C17,20-lyase). Each ZYTIGA tablet contains 250 mg of abiraterone acetate. Men with metastatic prostate cancer who have only received first line hormone therapy with LHRH agonist alone or LHRH agonist plus an anti-androgen. Patients who have developed castrate resistance to first line therapy and have then received second line hormone therapy of any kind (including flutamide, bicalutamide, nilutamide, ketoconazole, abiraterone, enzalutamide, ARN-509 and investigational anti-androgens) are not eligible for enrollment in this cohort. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Men with metastatic prostate cancer who have castrate resistant prostate cancer with inactivating somatic or germline mutations in the genes TP53, RB1 or PTEN identified using clinical grade sequencing of tumor tissue performed by qualified laboratory. Patients must have mutations in ≥2 of these genes to be eligible. Eligible patients must have progressed on first line hormone therapy with LHRH agonist alone and must have received at least one but not more than two second generation androgen ablative therapy (i.e. Abiraterone, Enzalutamide or Apalutamide). 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days.
    Measure Participants 30 29 29 0
    Baseline
    72.23
    (18.89)
    64.36
    (18.70)
    69.72
    (17.72)
    Cycle 1 Day 85
    71.76
    (19.20)
    73.97
    (19.96)
    73.40
    (17.98)
    10. Secondary Outcome
    Title Quality of Life (QoL) as Assessed by BPI
    Description Brief Pain Inventory (BPI) assesses the severity of pain and its impact on functioning with scales ranging from 0-10, with a higher score indicating a higher level of pain.
    Time Frame up to 18 months

    Outcome Measure Data

    Analysis Population Description
    Data was not collected for this outcome measure.
    Arm/Group Title Cohort A:Post-enzalutamide Cohort B: Post-abiraterone Cohort C: Castration Only Cohort D: Mutation
    Arm/Group Description Men with castration-resistant prostate cancer who have progressed on enzalutamide will be enrolled to this cohort. These patients will then receive intramuscular injections with testosterone cypionate 400 mg every 28 days or testosterone enanthate 400 mg every 28 days. Upon progression on testosterone cypionate or enanthate, men will be retreated with enzalutamide 160 mg by mouth daily. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Enzalutamide: XTANDI is provided as liquid-filled soft gelatin capsules for oral administration. Each capsule contains 40 mg of enzalutamide as a solution in caprylocaproyl polyoxylglycerides. Men with castration-resistant prostate cancer who have progressed on abiraterone will be enrolled to this cohort. These patients will then receive intramuscular injections with testosterone cypionate 400 mg every 28 days or testosterone enanthate 400 mg every 28 days. Upon progression on testosterone cypionate or enanthate, men will be retreated with abiraterone 1000 mg by mouth daily. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Abiraterone acetate: Abiraterone is an inhibitor of CYP17 (17α-hydroxylase/C17,20-lyase). Each ZYTIGA tablet contains 250 mg of abiraterone acetate. Men with metastatic prostate cancer who have only received first line hormone therapy with LHRH agonist alone or LHRH agonist plus an anti-androgen. Patients who have developed castrate resistance to first line therapy and have then received second line hormone therapy of any kind (including flutamide, bicalutamide, nilutamide, ketoconazole, abiraterone, enzalutamide, ARN-509 and investigational anti-androgens) are not eligible for enrollment in this cohort. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Men with metastatic prostate cancer who have castrate resistant prostate cancer with inactivating somatic or germline mutations in the genes TP53, RB1 or PTEN identified using clinical grade sequencing of tumor tissue performed by qualified laboratory. Patients must have mutations in ≥2 of these genes to be eligible. Eligible patients must have progressed on first line hormone therapy with LHRH agonist alone and must have received at least one but not more than two second generation androgen ablative therapy (i.e. Abiraterone, Enzalutamide or Apalutamide). 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days.
    Measure Participants 0 0 0 0
    11. Secondary Outcome
    Title Quality of Life (QoL) as Assessed by IIEF
    Description International Index of Erectile Function (IIEF-5) is a diagnostic tool for erectile dysfunction, with a total score range of 5-25, with the lowest score indicating a higher degree of dysfunction.
    Time Frame up to 18 months

    Outcome Measure Data

    Analysis Population Description
    20/30 participants in Cohort A, 21/29 participants in Cohort B, 25/29 participants in Cohort C were evaluable for this outcome measure. Data was not collected from participants in Cohort D.
    Arm/Group Title Cohort A:Post-enzalutamide Cohort B: Post-abiraterone Cohort C: Castration Only Cohort D: Mutation
    Arm/Group Description Men with castration-resistant prostate cancer who have progressed on enzalutamide will be enrolled to this cohort. These patients will then receive intramuscular injections with testosterone cypionate 400 mg every 28 days or testosterone enanthate 400 mg every 28 days. Upon progression on testosterone cypionate or enanthate, men will be retreated with enzalutamide 160 mg by mouth daily. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Enzalutamide: XTANDI is provided as liquid-filled soft gelatin capsules for oral administration. Each capsule contains 40 mg of enzalutamide as a solution in caprylocaproyl polyoxylglycerides. Men with castration-resistant prostate cancer who have progressed on abiraterone will be enrolled to this cohort. These patients will then receive intramuscular injections with testosterone cypionate 400 mg every 28 days or testosterone enanthate 400 mg every 28 days. Upon progression on testosterone cypionate or enanthate, men will be retreated with abiraterone 1000 mg by mouth daily. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Abiraterone acetate: Abiraterone is an inhibitor of CYP17 (17α-hydroxylase/C17,20-lyase). Each ZYTIGA tablet contains 250 mg of abiraterone acetate. Men with metastatic prostate cancer who have only received first line hormone therapy with LHRH agonist alone or LHRH agonist plus an anti-androgen. Patients who have developed castrate resistance to first line therapy and have then received second line hormone therapy of any kind (including flutamide, bicalutamide, nilutamide, ketoconazole, abiraterone, enzalutamide, ARN-509 and investigational anti-androgens) are not eligible for enrollment in this cohort. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Men with metastatic prostate cancer who have castrate resistant prostate cancer with inactivating somatic or germline mutations in the genes TP53, RB1 or PTEN identified using clinical grade sequencing of tumor tissue performed by qualified laboratory. Patients must have mutations in ≥2 of these genes to be eligible. Eligible patients must have progressed on first line hormone therapy with LHRH agonist alone and must have received at least one but not more than two second generation androgen ablative therapy (i.e. Abiraterone, Enzalutamide or Apalutamide). 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days.
    Measure Participants 30 29 29 0
    Baseline
    8
    (3.57)
    7.33
    (3.89)
    12.56
    (12.86)
    BAT C1D85
    24.13
    (21.63)
    24.94
    (19.71)
    22.44
    (15.53)
    12. Secondary Outcome
    Title Quality of Life (QoL) as Assessed by PANAS
    Description Positive and Negative Affect Schedule (PANAS) is a self-report measure that is made up of two mood scales, one measuring positive affect and the other measuring negative affect, with a total score range from 10-50 with a higher score on the positive scale indicating greater levels of positive affect and a lower score on the negative scale indicating less of a negative affect.
    Time Frame up to 18 months

    Outcome Measure Data

    Analysis Population Description
    20/30 participants in Cohort A, 18/29 participants in Cohort B, 25/29 participants in Cohort C were evaluable for this outcome measure. Data was not collected for Cohort D.
    Arm/Group Title Cohort A:Post-enzalutamide Cohort B: Post-abiraterone Cohort C: Castration Only Cohort D: Mutation
    Arm/Group Description Men with castration-resistant prostate cancer who have progressed on enzalutamide will be enrolled to this cohort. These patients will then receive intramuscular injections with testosterone cypionate 400 mg every 28 days or testosterone enanthate 400 mg every 28 days. Upon progression on testosterone cypionate or enanthate, men will be retreated with enzalutamide 160 mg by mouth daily. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Enzalutamide: XTANDI is provided as liquid-filled soft gelatin capsules for oral administration. Each capsule contains 40 mg of enzalutamide as a solution in caprylocaproyl polyoxylglycerides. Men with castration-resistant prostate cancer who have progressed on abiraterone will be enrolled to this cohort. These patients will then receive intramuscular injections with testosterone cypionate 400 mg every 28 days or testosterone enanthate 400 mg every 28 days. Upon progression on testosterone cypionate or enanthate, men will be retreated with abiraterone 1000 mg by mouth daily. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Abiraterone acetate: Abiraterone is an inhibitor of CYP17 (17α-hydroxylase/C17,20-lyase). Each ZYTIGA tablet contains 250 mg of abiraterone acetate. Men with metastatic prostate cancer who have only received first line hormone therapy with LHRH agonist alone or LHRH agonist plus an anti-androgen. Patients who have developed castrate resistance to first line therapy and have then received second line hormone therapy of any kind (including flutamide, bicalutamide, nilutamide, ketoconazole, abiraterone, enzalutamide, ARN-509 and investigational anti-androgens) are not eligible for enrollment in this cohort. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Men with metastatic prostate cancer who have castrate resistant prostate cancer with inactivating somatic or germline mutations in the genes TP53, RB1 or PTEN identified using clinical grade sequencing of tumor tissue performed by qualified laboratory. Patients must have mutations in ≥2 of these genes to be eligible. Eligible patients must have progressed on first line hormone therapy with LHRH agonist alone and must have received at least one but not more than two second generation androgen ablative therapy (i.e. Abiraterone, Enzalutamide or Apalutamide). 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days.
    Measure Participants 30 29 29 0
    Baseline
    46.15
    (10.55)
    48
    (11.47)
    41.24
    (14.35)
    BAT C1D85
    45.1
    (9.09)
    45.22
    (12.94)
    44.48
    (11.06)

    Adverse Events

    Time Frame Up to 2 years
    Adverse Event Reporting Description
    Arm/Group Title Cohort A:Post-enzalutamide Cohort B: Post-abiraterone Cohort C: Castration Only Cohort D: Mutation
    Arm/Group Description Men with castration-resistant prostate cancer who have progressed on enzalutamide will be enrolled to this cohort. These patients will then receive intramuscular injections with testosterone cypionate 400 mg every 28 days or testosterone enanthate 400 mg every 28 days. Upon progression on testosterone cypionate or enanthate, men will be retreated with enzalutamide 160 mg by mouth daily. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Enzalutamide: XTANDI is provided as liquid-filled soft gelatin capsules for oral administration. Each capsule contains 40 mg of enzalutamide as a solution in caprylocaproyl polyoxylglycerides. Men with castration-resistant prostate cancer who have progressed on abiraterone will be enrolled to this cohort. These patients will then receive intramuscular injections with testosterone cypionate 400 mg every 28 days or testosterone enanthate 400 mg every 28 days. Upon progression on testosterone cypionate or enanthate, men will be retreated with abiraterone 1000 mg by mouth daily. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Abiraterone acetate: Abiraterone is an inhibitor of CYP17 (17α-hydroxylase/C17,20-lyase). Each ZYTIGA tablet contains 250 mg of abiraterone acetate. Men with metastatic prostate cancer who have only received first line hormone therapy with LHRH agonist alone or LHRH agonist plus an anti-androgen. Patients who have developed castrate resistance to first line therapy and have then received second line hormone therapy of any kind (including flutamide, bicalutamide, nilutamide, ketoconazole, abiraterone, enzalutamide, ARN-509 and investigational anti-androgens) are not eligible for enrollment in this cohort. 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days. Men with metastatic prostate cancer who have castrate resistant prostate cancer with inactivating somatic or germline mutations in the genes TP53, RB1 or PTEN identified using clinical grade sequencing of tumor tissue performed by qualified laboratory. Patients must have mutations in ≥2 of these genes to be eligible. Eligible patients must have progressed on first line hormone therapy with LHRH agonist alone and must have received at least one but not more than two second generation androgen ablative therapy (i.e. Abiraterone, Enzalutamide or Apalutamide). 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 and will be administered at 400mg IM every 28 days. 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. Will be administered at 400mg IM every 28 days.
    All Cause Mortality
    Cohort A:Post-enzalutamide Cohort B: Post-abiraterone Cohort C: Castration Only Cohort D: Mutation
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/30 (3.3%) 0/29 (0%) 1/29 (3.4%) 0/8 (0%)
    Serious Adverse Events
    Cohort A:Post-enzalutamide Cohort B: Post-abiraterone Cohort C: Castration Only Cohort D: Mutation
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/30 (10%) 4/29 (13.8%) 5/29 (17.2%) 1/8 (12.5%)
    Blood and lymphatic system disorders
    disseminated intravascular coagulation 0/30 (0%) 0 1/29 (3.4%) 1 0/29 (0%) 0 0/8 (0%) 0
    Cardiac disorders
    myocardial infarction 1/30 (3.3%) 1 0/29 (0%) 0 1/29 (3.4%) 1 0/8 (0%) 0
    Cardiac Arrest 0/30 (0%) 0 0/29 (0%) 0 1/29 (3.4%) 1 0/8 (0%) 0
    Gastrointestinal disorders
    Lower gastrointestinal hemorrhage 0/30 (0%) 0 0/29 (0%) 0 1/29 (3.4%) 1 0/8 (0%) 0
    Infections and infestations
    Urinary Tract Infection 0/30 (0%) 0 0/29 (0%) 0 0/29 (0%) 0 1/8 (12.5%) 1
    Metabolism and nutrition disorders
    Pancreatitis, elevated lipase, amylase 1/30 (3.3%) 1 0/29 (0%) 0 0/29 (0%) 0 0/8 (0%) 0
    Nervous system disorders
    Neurological Symptoms 0/30 (0%) 0 1/29 (3.4%) 1 0/29 (0%) 0 0/8 (0%) 0
    stroke 0/30 (0%) 0 0/29 (0%) 0 1/29 (3.4%) 1 0/8 (0%) 0
    Renal and urinary disorders
    Urine Retention 0/30 (0%) 0 1/29 (3.4%) 1 0/29 (0%) 0 0/8 (0%) 0
    Acute Renal Insufficiency 1/30 (3.3%) 1 0/29 (0%) 0 0/29 (0%) 0 0/8 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Pneumonia 0/30 (0%) 0 1/29 (3.4%) 1 0/29 (0%) 0 0/8 (0%) 0
    dyspnea 0/30 (0%) 0 0/29 (0%) 0 1/29 (3.4%) 1 0/8 (0%) 0
    Other (Not Including Serious) Adverse Events
    Cohort A:Post-enzalutamide Cohort B: Post-abiraterone Cohort C: Castration Only Cohort D: Mutation
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 30/30 (100%) 29/29 (100%) 29/29 (100%) 8/8 (100%)
    Blood and lymphatic system disorders
    Increased Hemoglobin 11/30 (36.7%) 11 0/29 (0%) 0 0/29 (0%) 0 0/8 (0%) 0
    Anemia 5/30 (16.7%) 16 7/29 (24.1%) 10 0/29 (0%) 0 2/8 (25%) 2
    polycythemia 0/30 (0%) 0 0/29 (0%) 0 1/29 (3.4%) 1 0/8 (0%) 0
    Elevated hematocrit 1/30 (3.3%) 1 0/29 (0%) 0 0/29 (0%) 0 0/8 (0%) 0
    Eye disorders
    eye discorder 3/30 (10%) 3 1/29 (3.4%) 1 0/29 (0%) 0 0/8 (0%) 0
    Gastrointestinal disorders
    nausea 7/30 (23.3%) 9 4/29 (13.8%) 4 1/29 (3.4%) 1 1/8 (12.5%) 1
    abdominal pain 3/30 (10%) 3 1/29 (3.4%) 1 3/29 (10.3%) 3 0/8 (0%) 0
    bowel obstruction 0/30 (0%) 0 1/29 (3.4%) 1 1/29 (3.4%) 1 0/8 (0%) 0
    diarrhea 1/30 (3.3%) 1 0/29 (0%) 0 3/29 (10.3%) 3 1/8 (12.5%) 1
    constipation 3/30 (10%) 3 3/29 (10.3%) 4 1/29 (3.4%) 1 1/8 (12.5%) 2
    bloating 0/30 (0%) 0 0/29 (0%) 0 0/29 (0%) 0 1/8 (12.5%) 1
    General disorders
    fatigue 17/30 (56.7%) 23 5/29 (17.2%) 5 5/29 (17.2%) 5 0/8 (0%) 0
    edema 4/30 (13.3%) 5 8/29 (27.6%) 12 7/29 (24.1%) 8 1/8 (12.5%) 3
    fever 1/30 (3.3%) 1 2/29 (6.9%) 2 0/29 (0%) 0 1/8 (12.5%) 1
    chest pain 2/30 (6.7%) 2 2/29 (6.9%) 2 2/29 (6.9%) 2 0/8 (0%) 0
    cold symptoms 2/30 (6.7%) 2 0/29 (0%) 0 2/29 (6.9%) 2 0/8 (0%) 0
    Hepatobiliary disorders
    gallstone 1/30 (3.3%) 1 0/29 (0%) 0 0/29 (0%) 0 0/8 (0%) 0
    Infections and infestations
    sinusitis 3/30 (10%) 4 0/29 (0%) 0 0/29 (0%) 0 0/8 (0%) 0
    Injury, poisoning and procedural complications
    fall 3/30 (10%) 3 0/29 (0%) 0 0/29 (0%) 0 0/8 (0%) 0
    Investigations
    elevated ALK Phos 0/30 (0%) 0 3/29 (10.3%) 3 0/29 (0%) 0 0/8 (0%) 0
    weight loss 4/30 (13.3%) 4 3/29 (10.3%) 3 0/29 (0%) 0 0/8 (0%) 0
    Creatinine Increased 3/30 (10%) 4 1/29 (3.4%) 1 1/29 (3.4%) 2 1/8 (12.5%) 1
    High cholesterol 3/30 (10%) 3 0/29 (0%) 0 0/29 (0%) 0 0/8 (0%) 0
    Elevated liver enzymes 1/30 (3.3%) 1 0/29 (0%) 0 0/29 (0%) 0 0/8 (0%) 0
    Elevated AST 0/30 (0%) 0 1/29 (3.4%) 1 0/29 (0%) 0 0/8 (0%) 0
    Elevated troponin 0/30 (0%) 0 0/29 (0%) 0 1/29 (3.4%) 1 0/8 (0%) 0
    Metabolism and nutrition disorders
    anorexia 3/30 (10%) 3 5/29 (17.2%) 7 1/29 (3.4%) 1 1/8 (12.5%) 1
    Elevated potassium 1/30 (3.3%) 1 0/29 (0%) 0 0/29 (0%) 0 0/8 (0%) 0
    Elevated Glucose 0/30 (0%) 0 1/29 (3.4%) 1 0/29 (0%) 0 0/8 (0%) 0
    Musculoskeletal and connective tissue disorders
    Musculoskeletal pain 12/30 (40%) 39 8/29 (27.6%) 23 11/29 (37.9%) 22 4/8 (50%) 7
    Nervous system disorders
    headache 3/30 (10%) 3 5/29 (17.2%) 5 1/29 (3.4%) 1 0/8 (0%) 0
    Syncope 2/30 (6.7%) 2 0/29 (0%) 0 0/29 (0%) 0 1/8 (12.5%) 1
    dizziness 4/30 (13.3%) 4 1/29 (3.4%) 1 0/29 (0%) 0 2/8 (25%) 2
    Taster change 1/30 (3.3%) 1 0/29 (0%) 0 0/29 (0%) 0 0/8 (0%) 0
    Psychiatric disorders
    insomnia 1/30 (3.3%) 1 2/29 (6.9%) 2 3/29 (10.3%) 3 0/8 (0%) 0
    irritability 0/30 (0%) 0 0/29 (0%) 0 2/29 (6.9%) 2 0/8 (0%) 0
    anxiety 1/30 (3.3%) 1 0/29 (0%) 0 0/29 (0%) 0 0/8 (0%) 0
    Renal and urinary disorders
    Hematuria 0/30 (0%) 0 0/29 (0%) 0 0/29 (0%) 0 2/8 (25%) 2
    Urinary tract infection 0/30 (0%) 0 0/29 (0%) 0 1/29 (3.4%) 2 2/8 (25%) 3
    Reproductive system and breast disorders
    Breast Tenderness 5/30 (16.7%) 5 5/29 (17.2%) 6 6/29 (20.7%) 6 0/8 (0%) 0
    gynecomastia 4/30 (13.3%) 4 0/29 (0%) 0 1/29 (3.4%) 1 1/8 (12.5%) 1
    urine obstruction 0/30 (0%) 0 2/29 (6.9%) 2 1/29 (3.4%) 1 0/8 (0%) 0
    Erectile dysfunction 0/30 (0%) 0 1/29 (3.4%) 1 0/29 (0%) 0 0/8 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    dyspnea 0/30 (0%) 0 0/29 (0%) 0 2/29 (6.9%) 2 0/8 (0%) 0
    cough 5/30 (16.7%) 6 4/29 (13.8%) 6 0/29 (0%) 0 0/8 (0%) 0
    Shortness of breath 1/30 (3.3%) 1 0/29 (0%) 0 0/29 (0%) 0 0/8 (0%) 0
    Skin and subcutaneous tissue disorders
    rash 5/30 (16.7%) 6 2/29 (6.9%) 2 0/29 (0%) 0 0/8 (0%) 0
    pruritis 4/30 (13.3%) 4 0/29 (0%) 0 0/29 (0%) 0 0/8 (0%) 0
    pain at injection site 0/30 (0%) 0 2/29 (6.9%) 0 1/29 (3.4%) 1 0/8 (0%) 0
    increased hair growth 0/30 (0%) 0 0/29 (0%) 0 3/29 (10.3%) 3 0/8 (0%) 0
    Vascular disorders
    Hypertension 7/30 (23.3%) 24 4/29 (13.8%) 8 6/29 (20.7%) 6 0/8 (0%) 0
    hot flashes 5/30 (16.7%) 6 4/29 (13.8%) 4 2/29 (6.9%) 4 1/8 (12.5%) 1

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT 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.

    Results Point of Contact

    Name/Title Samuel Denmeade, M.D.
    Organization Johns Hopkins University School of Medicine
    Phone 410-502-8341
    Email denmesa@jhmi.edu
    Responsible Party:
    Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    ClinicalTrials.gov Identifier:
    NCT02090114
    Other Study ID Numbers:
    • J1416
    • NA_00093344
    • 1R01CA184012-01
    First Posted:
    Mar 18, 2014
    Last Update Posted:
    Jun 27, 2022
    Last Verified:
    Jun 1, 2022