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


Condition: Prostate Cancer

Intervention:

  • Drug: Testosterone cypionate
  • Drug: Testosterone Enanthate
  • Drug: Abiraterone acetate
  • Drug: Enzalutamide (Cohort A = CLOSED TO ACCRUAL)

Purpose: Single-arm, single site, open label study of the effects of parenteral testosterone followed by enzalutamide or abiraterone or castration-only therapy in men with metastatic CRPC who previously progressed on one of these forms of therapy. The study will enroll three cohorts of patients: men with metastatic CRPC who have progressed on enzalutamide (Cohort A); men with metastatic CRPC who have progressed on abiraterone acetate (Cohort B); and men with metastatic CRPC who have progressed on first line castration-only therapy (Cohort C).

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02090114

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Primary Outcome Measures:

  • Measure: Prostate Specific Antigen (PSA) response to Bipolar Androgen Therapy (BAT)
  • Time Frame: up to 18 months
  • Safety Issue:
  • Measure: PSA response to enzalutamide or abiraterone acetate post Bipolar Androgen Therapy
  • Time Frame: up to 24 months
  • Safety Issue:
  • Measure: PSA response to castrate levels of testosterone post Bipolar Androgen Therapy
  • Time Frame: up to 18 months
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: PSA progression on enzalutamide or abiraterone acetate or castrate levels post-BAT
  • Time Frame: up to 18 months
  • Safety Issue:
  • Measure: PSA progression on BAT (Bipolar Androgen Therapy )
  • Time Frame: up to 18 months
  • Safety Issue:
  • Measure: Disease response as defined by RECIST 1.1 (soft tissue lesions) and PCWG2 criteria (bone lesions)
  • Time Frame: up to 18 months
  • Safety Issue:
  • Measure: Initiation of docetaxel chemotherapy
  • Time Frame: up to 18 months
  • Safety Issue:
  • Measure: Quality of Life (QoL) as assessed by FACIT-F score
  • Time Frame: Change from baseline to 18 months
  • Safety Issue:
  • Measure: Safety and Tolerability as assessed by Number of Participants with Adverse Events
  • Time Frame: 18 months
  • Safety Issue:
  • Measure: Fasting glucose
  • Time Frame: 18 months
  • Safety Issue:
  • Measure: Hemoglobin A1c
  • Time Frame: 18 months
  • Safety Issue:
  • Measure: Fasting insulin
  • Time Frame: 18 months
  • Safety Issue:
  • Measure: Serum C-telopeptide
  • Time Frame: 18 months
  • Safety Issue:
  • Measure: Osteocalcin
  • Time Frame: On average at 18 months
  • Safety Issue:
  • Measure: Effect of treatment with testosterone and abiraterone acetate or enzalutamide on Bone Scan with SPECT CT
  • Time Frame: 18 months
  • Safety Issue:
  • Measure: Quality of Life (QoL) as assessed by RANDSF-36
  • Time Frame: Change from baseline to 18 months
  • Safety Issue:
  • Measure: Quality of Life (QoL) as assessed by BPI
  • Time Frame: Change from baseline to 18 months
  • Safety Issue:
  • Measure: Quality of Life (QoL) as assessed by IIEF
  • Time Frame: Change from baseline to 18 months
  • Safety Issue:
  • Measure: Quality of Life (QoL) as assessed by PANAS
  • Time Frame: Change from baseline to 18 months
  • Safety Issue:

Estimated Enrollment: 90

Study Start Date: June 2014

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: Male

Inclusion Criteria:

  1. Performance status ≤2
  2. Age ≥18 years
  3. Histologically-confirmed adenocarcinoma of the prostate
  4. Progressing on continuous androgen ablative therapy (either surgical castration or LHRH agonist).
  5. Documented castrate level of serum testosterone (<50 ng/dl).
  6. For Cohorts A and B, patients must have progressed on prior treatment with enzalutamide or abiraterone acetate + prednisone (by PSA criteria or radiographically).
  7. 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.
  8. 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.
  9. Patients with rising PSA on two successive measurements at least two weeks apart.
  10. For Cohort A (enzalutamide) and Cohort B (abiraterone acetate):
  11. Prior treatment with up to 2 additional second line hormone therapies, including ketoconazole is allowed.
  12. 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).
  13. Patients must be withdrawn from enzalutamide or abiraterone acetate for ≥ 4 weeks and have documented PSA increase after the withdrawal period.
  14. Patients receiving prednisone in conjunction with abiraterone acetate must be weaned off prednisone prior to starting BAT.
  15. For Cohort C (castration-only):
  16. Patients must continue on castrating therapy throughout BAT treatment.
  17. 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.
  18. 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.
  19. Acceptable liver function:
  20. Bilirubin < 2.5 times institutional upper limit of normal (ULN)
  21. AST (SGOT) and ALT (SGPT) < 2.5 times ULN
  22. Acceptable renal function: a. Serum creatinine < 2.5 times ULN, OR
  23. Acceptable hematologic status:
  24. Absolute neutrophil count (ANC) ≥ 1500 cells/mm3 (1.5 ×109/L)
  25. Platelet count ≥ 100,000 platelet/mm3 (100 ×109/L)
  26. Hemoglobin ≥ 9 g/dL.
  27. At least 4 weeks since prior surgery with full recovery (no persistent toxicity ≥ Grade 1).
  28. Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

  1. Pain due to metastatic prostate cancer requiring opioid analgesics.
  2. >5 sites of visceral disease in lung or liver (nonspecific lung nodules ≤1 cm in diameter are permitted).
  3. Prior treatment with docetaxel or cabazitaxel for metastatic castration-resistant prostate cancer is prohibited.
  4. Requires urinary catheterization for voiding due to obstruction secondary to prostatic enlargement thought to be due to prostate cancer or benign prostatic hyperplasia.
  5. 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).
  6. 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.
  7. Active uncontrolled infection, including known history of AIDS or hepatitis B or C.
  8. Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule.
  9. Prior history of a thromboembolic event within the last two years and not currently on systemic anticoagulation.
  10. Hematocrit >50%, untreated severe obstructive sleep apnea, uncontrolled or poorly controlled heart failure [per Endocrine Society Clinical Practice Guidelines (67)].

Contact:

  • Irina Rifkind, RN, MSN
  • 410-502-2043

Location:

  • The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  • Baltimore Maryland 21231 United States

View trial on ClinicalTrials.gov


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