NCT03009981

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

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

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 504 (actual)
• Sponsor: Alliance Foundation Trials, LLC. · Academic / Other
• Sex: Male
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a 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.

Detailed description

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 LHRH analogue monotherapy (degarelix or leuprolide), (2) Experimental arm consisting of apalutamide in combination with LHRH analogue, and (3) Experimental arm consisting of apalutamide, abiraterone acetate + prednisone, and LHRH analogue. Patients will be treated for a maximum duration of 52 weeks and then enter follow up phase until the time of PSA progression, development of metastasis, or patient withdrawal from study, whichever occurs first. Patients with PSA progression will be followed long term until the development of castration resistance, first metastasis, and death. The primary endpoint of the study is PSA progression-free survival in the intent-to-treat patient population. PSA progression during the 52-week treatment period is defined as a rising PSA confirmed on repeat measurement, and at least 25% and 2 ng/mL above nadir or baseline, whichever is lower. PSA progression during follow up defined as PSA \> 0.2 ng/mL confirmed by repeat measurement at least 2 weeks later. Secondary study endpoints include PSA progression-free survival in testosterone-evaluable population, 36-month PSA progression-free survival rate in both intent-to-treat and testosterone-evaluable populations, time to testosterone recovery, time to castration resistance, metastasis-free survival, quality of life, and safety. Each experimental arm will be compared against the control arm in pair-wise fashion. The study is not powered to detect differences in primary or secondary endpoints between the two experimental arms.

Conditions

• Prostate Cancer

Interventions

Type	Name	Description
DRUG	Apalutamide	Take apalutamide 240 mg (four 60 mg tablets) orally once daily, starting on C1D1 and continuing throughout 52-week treatment period.
DRUG	LHRH Analogue	Patients will receive a LHRH analogue therapy of either Degarelix OR Leuprolide with bicalutamide. Degarelix: Patients will receive subcutaneous injections every 28 days (+/- 3 days). Patients will receive a loading dose of 240 mg (two 120 mg injections) on C1D1, followed by maintenance dose of 80 mg on Day 1 of subsequent cycles. Leuprolide: Patients treated with leuprolide will receive a 7.5 mg IM injection on C1D1. Patients in arm A ONLY will take this in combination with bicalutamide 50 mg orally once daily starting on C1D1 and continuing for 28 days through completion of cycle 1. Starting on C2D1, patients will continue on one of the following two treatments at investigator discretion: 1. Leuprolide 7.5 mg IM injection on Day 1 of subsequent cycles without concurrent bicalutamide. OR: 2. Leuprolide 22.5 mg IM injection at the following visits without concurrent bicalutamide: C2D1, C5D1, C8D1, and C11D1.
DRUG	Abiraterone Acetate	Take abiraterone acetate 1000 mg (four 250 mg tablets) orally once daily, starting on C1D1 and continuing throughout 52-week treatment period.
DRUG	Prednisone	Take two prednisone 5 mg tablets daily, starting on C1D1 and continuing throughout the 52-week treatment period. Following completion of treatment period, patients will taper off prednisone per institutional guidelines. Suggested tapering plan: prednisone 5 mg daily for 7 days, then 2.5 mg daily for 7 days before discontinuing.

Timeline

• Start date: 2017-03-06
• Primary completion: 2025-06-25
• Completion: 2025-06-25
• First posted: 2017-01-04
• Last updated: 2025-12-18

Locations

69 sites across 1 country: United States

Regulatory

• FDA-regulated drug study