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

December 16, 2025 updated by: Alliance Foundation Trials, LLC.

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

504

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • The Mayo Clinic - Phoenix
    • California
      • Chula Vista, California, United States, 91911
        • Sharp Memorial Hospital
      • Duarte, California, United States, 91010
        • City Of Hope National Medical Center
      • Fremont, California, United States, 94538
        • Palo Alto Medical Foundation
      • Fresno, California, United States, 93703
        • VA Central California Health Care System
      • La Mesa, California, United States, 91942
        • Sharp Memorial Hospital
      • Mountain View, California, United States, 94040
        • Palo Alto Medical Foundation
      • Palo Alto, California, United States, 94301
        • Palo Alto Medical Foundation
      • San Diego, California, United States, 92123
        • Sharp Memorial Hospital
      • San Diego, California, United States, 92093
        • University of California San Diego - Moores Cancer Center
      • San Francisco, California, United States, 94158
        • University of California San Francisco
      • Santa Cruz, California, United States, 95065
        • Palo Alto Medical Foundation
      • St. Helena, California, United States, 94574
        • Adventist Health St. Helena/St. Helena Hospital/Martin O'Neil Cancer Center
      • Sunnyvale, California, United States, 94086
        • Palo Alto Medical Foundation
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20007
        • Georgetown University Medical Center
      • Washington D.C., District of Columbia, United States, 20007
        • MedStar Washington Hospital Center
    • Hawaii
      • Honolulu, Hawaii, United States, 96813
        • University of Hawaii Cancer Center
      • ‘Aiea, Hawaii, United States, 96701
        • Pali Momi Medical Center
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago Comprehensive Cancer Center
      • Chicago, Illinois, United States, 606012
        • Rush University Medical Center
      • Evanston, Illinois, United States, 60201
        • NorthShore University Health System
      • Maywood, Illinois, United States, 60153
        • Loyola University
      • Quincy, Illinois, United States, 62301
        • Quincy Medical Group
      • Urbana, Illinois, United States, 61801
        • Carle Cancer Center
    • Kansas
      • Wichita, Kansas, United States, 67214
        • Cancer Center of Kansas
    • Maine
      • Brewer, Maine, United States, 04412
        • Eastern Maine Medical Center
      • Kennebunk, Maine, United States, 04043
        • New England Cancer Specialists
      • Scarborough, Maine, United States, 04074
        • New England Cancer Specialists
      • Topsham, Maine, United States, 04086
        • New England Cancer Specialists
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Cancer Institute
      • Milford, Massachusetts, United States, 01757
        • Dana Farber Cancer Institute
      • South Weymouth, Massachusetts, United States, 02190
        • Dana Farber Cancer Institute
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota
      • Saint Louis Park, Minnesota, United States, 55416
        • Metro Minnesota Community Oncology Research Consortium
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • Nebraska
      • Omaha, Nebraska, United States, 68114
        • Nebraska Methodist Hospital
    • Nevada
      • Las Vegas, Nevada, United States, 89106
        • Nevada Cancer Research Foundation
    • New Hampshire
      • Concord, New Hampshire, United States, 03301
        • New Hampshire Oncology & Hematology
      • Hooksett, New Hampshire, United States, 03106
        • New Hampshire Oncology & Hematology
    • New Jersey
      • Basking Ridge, New Jersey, United States, 07920
        • Memorial Sloan Kettering Basking Ridge
      • Middletown, New Jersey, United States, 07748
        • Memorial Sloan Kettering Cancer Center
      • Morristown, New Jersey, United States, 07962
        • Atlantic Health System/Morristown Medical Center
    • New Mexico
      • Albuquerque, New Mexico, United States, 87109
        • New Mexico Oncology Hematology Consultants
      • Albuquerque, New Mexico, United States, 87131
        • University of New Mexico Comprehensive Cancer Center
      • Las Cruces, New Mexico, United States, 88011
        • Memorial Medical Center- Cancer Center
      • Santa Fe, New Mexico, United States, 87505
        • Christus St. Vincent's Regional Cancer Center
    • New York
      • Buffalo, New York, United States, 14263
        • Roswell Park Cancer Institute
      • Buffalo, New York, United States, 14215
        • VA Western New York
      • Commack, New York, United States, 11725
        • Memorial Sloan Kettering Cancer Center
      • Harrison, New York, United States, 11533
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, United States, 10461
        • Montefiore Medical Center
      • New York, New York, United States, 10065
        • Weill Cornell Medical Ctr - New York Presbyterian Hospital
      • Syracuse, New York, United States, 13210
        • SUNY Upstate Medical University
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27514
        • University of North Carolina Hospital
      • Charlotte, North Carolina, United States, 28204
        • Novant Health Presbyterian Medical Center
      • Salisbury, North Carolina, United States, 28144
        • VA Salisbury
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University Health Sciences
    • Ohio
      • Centerville, Ohio, United States, 45459
        • Dayton Physicians Miami Valley South
      • Columbus, Ohio, United States, 43210
        • The Ohio State University Comprehensive Cancer Center
      • Toledo, Ohio, United States, 43623
        • The Toledo Clinic
    • Oklahoma
      • Tulsa, Oklahoma, United States, 74146
        • Oklahoma Cancer Specialists and Research Institute
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health & Science University
      • Portland, Oregon, United States, 97213
        • Providence Portland Medical Center
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • University of Pittsburgh Medical Center
    • South Carolina
      • Spartanburg, South Carolina, United States, 29303
        • Spartanburg Medical Center/Gibbs Cancer Center
    • Texas
      • Houston, Texas, United States, 77030
        • University of Texas MD Anderson Cancer Center
    • Wisconsin
      • Marshfield, Wisconsin, United States, 54449
        • Marshfield Clinic Cancer Center
      • Milwaukee, Wisconsin, United States, 53226
        • Froedtert Hospital/Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 6-12 months prior to randomization, with a minimum of 3 values separated by at least 2 weeks apart. PSA values obtained prior to therapeutic interventions (e.g. salvage radiation) will be excluded. PSA doubling time to be estimated using Memorial Sloan Kettering Cancer Center online calculator (https://www.mskcc.org/nomograms/prostate/psa-doubling-time)
  • 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
  • Eastern Cooperative Oncology Group (ECOG) Performance Status grade 0 or 1
  • Age ≥ 18 years
  • Medications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to cycle 1 day 1
  • Agrees to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agrees to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug. Must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug.

  • Adequate organ function as defined by the following laboratory values at screening:

    • Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) < 2.5 x upper limit of normal (ULN)
    • Total serum bilirubin ≤1.5 x ULN. In subjects with Gilbert's syndrome, if total bilirubin is >1.5 × ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤1.5 × ULN, subject may be eligible)
    • Serum potassium ≥ 3.5 mmol/L. Supplementation and re-screening is allowed.
    • Estimated creatinine clearance > 45 ml/min using Cockroft-Gault equation
    • Platelets ≥ 100,000/microliter independent of transfusion and/or growth factors within 3 months prior to randomization
    • Hemoglobin ≥ 9.0 g/dL independent of transfusion and/or growth factors within 3 months prior to randomization
    • Serum albumin ≥ 3.0 g/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 cycle 1 day 1
  • 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)
  • 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
  • Baseline severe hepatic impairment (Child-Pugh Class B & C)
  • Intercurrent illness that is not controlled such as active infection, psychiatric illness/social situations that would limit compliance with study requirements
  • Any chronic medical condition requiring a higher dose of corticosteroid than equivalent of 5 mg prednisone/prednisolone once daily

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Arm A: Degarelix Monotherapy OR Leuprolide/Bicalutamide
Patients will receive degarelix OR leuprolide with bicalutamide.
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.
Other Names:
  • Degarelix (Firmagon)
  • Leuprolide (Lupron) and Bicalutamide
Experimental: Arm B: Degarelix/Apalutamide
Patients will receive apalutamide and either degarelix OR leuprolide. Patients on this arm will NOT take bicalutamide at any point in the treatment course.
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.
Other Names:
  • Degarelix (Firmagon)
  • Leuprolide (Lupron) and Bicalutamide
Drug: Apalutamide
Take apalutamide 240 mg (four 60 mg tablets) orally once daily, starting on C1D1 and continuing throughout 52-week treatment period.
Other Names:
  • Erleada
Experimental: Arm C: Degarelix/Apalutamide/Abiraterone/Prednisone
Patients will receive apalutamide and abiraterone acetate, in addition to either degarelix OR leuprolide. Patients on this arm will NOT take bicalutamide at any point in the treatment course.
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.
Other Names:
  • Degarelix (Firmagon)
  • Leuprolide (Lupron) and Bicalutamide
Drug: Apalutamide
Take apalutamide 240 mg (four 60 mg tablets) orally once daily, starting on C1D1 and continuing throughout 52-week treatment period.
Other Names:
  • Erleada
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.
Other Names:
  • Zytiga
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.
Other Names:
  • Deltasone

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PSA progression-free survival in the intent-to-treat population
Time Frame: 36 months
To compare PSA progression-free survival in each of the experimental arms (LHRH analogue + apalutamide; LHRH analogue + apalutamide +abiraterone acetate) versus the control arm (LHRH analogue) among all randomized patients (intent-to-treat population).
36 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PSA progression-free survival in the testosterone-evaluable population
Time Frame: 36 months
Compare PSA progression-free survival in testosterone-evaluable population in each experimental arm versus the control arm. Testosterone-evaluable population includes all patients who achieve serum testosterone recovery to > 50 ng/dL with subsequent PSA measurements sufficient for evaluation
36 months
PSA progression-free survival in both the intent-to-treat and testosterone-evaluable populations
Time Frame: 36 months
To compare the 36-month PSA progression-free survival rate in each experimental arm versus the control arm in both the intent-to-treat and testosterone-evaluable populations.
36 months
Serum testosterone
Time Frame: 12 months
To compare the time to recovery of serum testosterone to greater than 50 ng/dL in each experimental arm versus the control arm.
12 months
Time to castration resistance
Time Frame: 6 years
To compare the time to castration resistance in each experimental arm versus the control arm.
6 years
Metastasis-Free Survival
Time Frame: 6 years
To compare metastasis-free survival in each experimental arm versus the control arm.
6 years
Overall Survival
Time Frame: 6 years
To compare overall survival in each experimental arm versus the control arm.
6 years
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame: 6 years
To characterize the safety profile in each treatment arm
6 years
Quality of life Expanded Prostate Cancer Index Composite (EPIC)
Time Frame: 72 months
Expanded Prostate Cancer Index Composite (EPIC)
72 months
Quality of life Hot Flash Daily Interference Scale (HFRDIS)
Time Frame: 72 months
Hot Flash Daily Interference Scale (HFRDIS)
72 months
Quality of life EQ-5D-5L
Time Frame: 72 months
EQ-5D-5L
72 months
Quality of life PROMIS Fatigue
Time Frame: 72 months
PROMIS Fatigue
72 months
Quality-adjusted survival
Time Frame: 72 months
To compare the quality-adjusted survival (overall survival multiplied by utility score) of patients in each experimental arm versus the control arm.
72 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alliance Foundation Trials, LLC.

Collaborators

Janssen Research & Development, LLC

Investigators

  • Study Chair: Rahul Aggarwal, MD, University of California, San Francisco
  • Principal Investigator: Evanthia Evanthia Galanis, MD, Alliance Foundation Trials, LLC.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 6, 2017

Primary Completion (Actual)

June 25, 2025

Study Completion (Actual)

June 25, 2025

Study Registration Dates

First Submitted

January 3, 2017

First Submitted That Met QC Criteria

January 3, 2017

First Posted (Estimated)

January 4, 2017

Study Record Updates

Last Update Posted (Estimated)

December 18, 2025

Last Update Submitted That Met QC Criteria

December 16, 2025

Last Verified

October 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AFT-19

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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