A Phase 3 Study of Androgen Annihilation in High-Risk Biochemically Relapsed Prostate Cancer

Randomized, open-label, three-arm, phase 3 study in men with biochemically recurrent prostate cancer and PSA doubling time ≤ 9 months at the time of study entry. Patients will be stratified by PSA doubling time (< 3 months vs. 3-9 months) and randomized in 1:1:1 fashion to one of three treatment arms: (1) Control arm consisting of degarelix monotherapy, (2) Experimental arm consisting of apalutamide in combination with degarelix, and (3) Experimental arm consisting of apalutamide, abiraterone acetate + prednisone, and degarelix. Patients will be treated for a maximum duration of 52 weeks and then enter follow up phase until the time of PSA progression. Patients with PSA progression will be followed long term for development of castration resistance, first metastasis, and death.
Inclusion Criteria:
• Histologically confirmed prostate adenocarcinoma
• Prior radical prostatectomy
• Biochemically recurrent prostate cancer with PSA doubling time ≤ 9 months at the time of study entry. Calculation of PSA doubling time should include the use of all available PSA values obtained within past 12 months prior to randomization, with a minimum of 3 values separated by at least 2 weeks apart. PSA values obtained prior to localized therapy will be excluded. PSA doubling time to be estimated using Memorial Sloan Kettering Cancer Center online calculator (
• Prior adjuvant or salvage radiation or not a candidate for radiation based upon clinical assessment of disease characteristics and patient co-morbidities.
• Screening PSA > 0.5 ng/mL
• No definitive evidence of metastases on screening CT or MRI of abdomen/pelvis and radionuclide whole body bone scan per the judgment of the investigator. Abdominal and/or pelvic lymph nodes measuring 2 cm or less in short axis diameter are allowed. Lesions identified on other imaging modalities (e.g. PSMA or choline PET) that are not visualized on CT and/or MRI or radionuclide bone scan are allowed. Equivocal lesions on bone scan should be followed up with additional imaging as clinically indicated.
• Screening serum testosterone > 150 ng/dL

Exclusion Criteria:
• Prior androgen deprivation therapy and/or first generation anti-androgen (e.g. bicalutamide, nilutamide, flutamide) for biochemically recurrent prostate cancer. Prior ADT and/or first generation anti-androgen in the (neo)adjuvant and/or salvage setting before, during, and/or following radiation or surgery is allowed provided last effective dose of ADT and/or first-generation anti-androgen is > 9 months prior to date of randomization and total duration of prior therapy is ≤ 36 months.
• Prior treatment with CYP17 inhibitor (e.g. ketoconazole, abiraterone acetate, galeterone) or second generation androgen receptor antagonist including apalutamide or enzalutamide
• Prior chemotherapy for prostate cancer except if administered in neoadjuvant or adjuvant setting
• Use of 5-alpha reductase inhibitor within 42 days prior to randomization
• Use of investigational agent within 28 days prior to randomization
• Use of other prohibited medications within 7 days prior to cycle 1 day 1 on study (Arms B and C only) (see Appendix 1 for list of prohibited medications)
• Prior bilateral orchiectomy
• Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1year to randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign CNS or meningeal disease which may require treatment with surgery or radiation therapy)
• Uncontrolled hypertension
• Gastrointestinal disorder affecting absorption or the ability to swallow tablets
Phase III
Brendan Curti, M.D.
Alliance Foundations Trials (AFT), LLC
  • Oncology and Hematology Care Westside
  • Providence Cancer Institute Clackamas Clinic
  • Providence Cancer Institute Franz Clinic
  • Providence Cancer Institute Newberg Clinic