A Randomized Phase II Study Comparing Bipolar Androgen Therapy vs. Enzalutamide in Asymptomatic Men With Castration Resistant Metastatic Prostate Cancer

Condition: Castration Resistant Metastatic Prostate Cancer


  • Drug: Testosterone cypionate
  • Drug: Enzalutamide
  • Drug: Testosterone Enanthate

Purpose: Asymptomatic men with progressive metastatic CRPC post- treatment with abiraterone acetate (pre-chemotherapy for metastatic disease) will be treated on a randomized, multi-Institutional open label study to determine if treatment with intramuscular T given on a dose/schedule designed to result in rapid cycling from the polar extremes of supraphysiologic to near castrate levels [i.e. Bipolar Androgen Therapy (BAT)] will improve primary and secondary objectives vs. enzalutamide as standard therapy.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02286921

Sponsor: Sidney Kimmel Comprehensive Cancer Center

Primary Outcome Measures:

  • Measure: Radiographic Progression
  • Time Frame: 2 years
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: The number of adverse events and the severity of injection site reactions throughout the study in asymptomatic men with recurrent castrate resistant prostate cancer.
  • Time Frame: 2 years
  • Safety Issue:
  • Measure: PSA response rate
  • Time Frame: 2 years
  • Safety Issue:
  • Measure: Objective response rate
  • Time Frame: 2 years
  • Safety Issue:
  • Measure: Time to PSA progression
  • Time Frame: 2 years
  • Safety Issue:
  • Measure: PSA response rate to enzalutamide post-BAT
  • Time Frame: 2 years
  • Safety Issue:
  • Measure: PSA response rate to BAT post-enzalutamide
  • Time Frame: 2 years
  • Safety Issue:
  • Measure: Quality of Life Survey (This is a composite outcome measure)
  • Time Frame: 2 years
  • Safety Issue:

Estimated Enrollment: 180

Study Start Date: January 2015

Phase: Phase 2


  • Age: minimum 18 Years maximum 80 Years
  • Gender: Male

Inclusion Criteria:

  1. ECOG Performance status ≤2
  2. Age ≥18 years
  3. Histologically-confirmed adenocarcinoma of the prostate
  4. Treated with continuous androgen ablative therapy (either surgical castration or LHRH agonist/antagonist)
  5. Documented castrate level of serum testosterone (<50 ng/dl)
  6. Metastatic disease radiographically documented by CT/MRI or bone scan.
  7. Must have had disease progression while on abiraterone acetate alone or abiraterone acetate in combination with other investigational agents based on: PSA progression defined as an increase in PSA, as determined by 2 separate measurements taken at least 1 week apart And/Or Radiographic disease progression, based on RECIST 1.1 in patients with measurable soft tissue lesions, or PCWG2 for patients with bone disease
  8. Screening PSA must be ≥ 1.0 ng/mL.
  9. Prior treatment with additional second line hormone therapies is allowed.
  10. No prior treatment with enzalutamide, ARN-509, ODM-201, galeterone or other investigational AR targeted treatment is allowed.
  11. 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.
  12. Prior treatment with Provenge vaccine and 223Radium (Xofigo) is allowed if >4 weeks from last dose.
  13. Patients must be withdrawn from abiraterone for ≥ 2 weeks.
  14. Patients must be weaned off prednisone and be off therapy for ≥ 1 week prior to starting therapy.
  15. Acceptable liver function:
  16. Bilirubin < 2.5 times institutional upper limit of normal (ULN)
  17. AST (SGOT) and ALT (SGPT) < 2.5 times ULN
  18. Acceptable renal function: a. Serum creatinine < 2.5 times ULN
  19. Acceptable hematologic status:
  20. Absolute neutrophil count (ANC) ≥ 1500 cells/mm3 (1.5 ×109/L)
  21. Platelet count ≥ 100,000 platelet/mm3 (100 ×109/L)
  22. Hemoglobin ≥ 9 g/dL.
  23. At least 4 wks since prior radiation.
  24. Ability to understand and willingness to sign a written informed consent document.
  25. Patients on either treatment arm will be considered for crossover if they demonstrate evidence of radiographic disease progression.

Exclusion Criteria:

  1. Pain due to metastatic prostate cancer requiring treatment intervention.
  2. Prior treatment with enzalutamide is prohibited
  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 well documented to be due to prostate cancer or benign prostatic hyperplasia (BPH).
  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, severe and extensive spinal metastases with concern over spinal cord compression, extensive liver metastases)
  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 HIV/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. Patients receiving anticoagulation therapy with Coumadin are not eligible for study. [Patients on non-coumadin anticoagulants (Lovenox, Xarelto, etc.) are eligible for study. Patients on Coumadin who can be transitioned to lovenox prior to starting study treatments will be eligible].
  10. Patients with prior history of a thromboembolic event within the last 12 months that is not being treated with systemic anticoagulation are excluded.
  11. Patients allergic to sesame seed oil or cottonseed oil are excluded.
  12. Major surgery (eg, requiring general anesthesia) within 3 weeks before screening, or has not fully recovered from prior surgery (ie, unhealed wound). Note: subjects with planned surgical procedures to be conducted under local anesthesia may participate.


  • Kathy Schultz, RN
  • 410-614-9482


  • SKCCC at Johns Hopkins
  • Baltimore Maryland 21205 United States

View trial on ClinicalTrials.gov


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