A Randomized Phase II Study Comparing Sequential High Dose Testosterone and Enzalutamide to Enzalutamide Alone in Asymptomatic Men With Castration Resistant Metastatic Prostate Cancer
Asymptomatic men without pain due to prostate cancer progressing with metastatic CRPC after treatment with combination or sequential ADT + Abi will be treated on a randomized, open label study to determine if sequential treatment with high dose T and Enza will improve primary and secondary objectives vs. continuous Enza as standard therapy.
• ECOG Performance status ≤2.
• Age ≥18 years.
• Histologically-confirmed adenocarcinoma of the prostate.
• Treated with continuous androgen ablative therapy (either surgical castration or LHRH agonist/antagonist).
• Documented castrate level of serum testosterone (\<50 ng/dl).
• Metastatic disease radiographically documented by CT or bone scan.
• Must have had disease progression while on combination of abiraterone acetate plus ADT either given concurrently or sequentially 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 PCWG3 for patients with bone disease
• Screening PSA must be ≥ 1.0 ng/mL.
• Patients with soft tissue lesion amenable to biopsy must agree to biopsy collection pre-treatment and at a defined point on treatment to perform tumor tissue analysis.
⁃ No prior treatment with enzalutamide, apalutamide, darolutamide, or other investigational AR targeted treatment is allowed.
⁃ Prior treatment with testosterone is allowed.
⁃ Prior treatment with one chemotherapy regimen with docetaxel (≤ 6 doses) for hormonesensitive prostate cancer is allowed.
⁃ Prior treatment with Provenge vaccine and 223Radium (Xofigo) is allowed if \>4 weeks from last dose.
⁃ Patients must be withdrawn from abiraterone for ≥ 2 weeks.
⁃ Attempts must be made to wean patients off prednisone prior to starting therapy. Patients who cannot be weaned due to symptoms may continue on lowest dose of prednisone achieved during weaning period.
⁃ 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:
⁃ a. Serum creatinine \< 2.5 times ULN
⁃ Acceptable hematologic status:
• Absolute neutrophil count (ANC) ≥ 1500 cells/mm3 (1.5 ×109/L)
∙ Platelet count ≥ 100,000 platelet/mm3 (100 ×109/L)
∙ Hemoglobin ≥ 8 g/dL.
⁃ At least 4 weeks since prior radiation or chemotherapy.
⁃ Ability to understand and willingness to sign a written informed consent document.