A Study of Androgen Annihilation in High-Risk Biochemically Relapsed Prostate Cancer
NCT ID: NCT03009981
Last Updated: 2025-12-18
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE3
504 participants
INTERVENTIONAL
2017-03-06
2025-06-25
Brief Summary
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Detailed Description
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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
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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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.
Apalutamide
Take apalutamide 240 mg (four 60 mg tablets) orally once daily, starting on C1D1 and continuing throughout 52-week treatment period.
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.
Abiraterone Acetate
Take abiraterone acetate 1000 mg (four 250 mg tablets) orally once daily, starting on C1D1 and continuing throughout 52-week treatment period.
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.
Arm A: Degarelix Monotherapy OR Leuprolide/Bicalutamide
Patients will receive degarelix OR leuprolide with bicalutamide.
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.
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.
Apalutamide
Take apalutamide 240 mg (four 60 mg tablets) orally once daily, starting on C1D1 and continuing throughout 52-week treatment period.
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.
Interventions
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Apalutamide
Take apalutamide 240 mg (four 60 mg tablets) orally once daily, starting on C1D1 and continuing throughout 52-week treatment period.
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.
Abiraterone Acetate
Take abiraterone acetate 1000 mg (four 250 mg tablets) orally once daily, starting on C1D1 and continuing throughout 52-week treatment period.
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 Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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 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
18 Years
MALE
No
Sponsors
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Janssen Research & Development, LLC
INDUSTRY
Alliance Foundation Trials, LLC.
OTHER
Responsible Party
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Principal Investigators
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Evanthia Evanthia Galanis, MD
Role: PRINCIPAL_INVESTIGATOR
Alliance Foundation Trials, LLC.
Rahul Aggarwal, MD
Role: STUDY_CHAIR
University of California, San Francisco
Locations
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The Mayo Clinic - Phoenix
Phoenix, Arizona, United States
Sharp Memorial Hospital
Chula Vista, California, United States
City of Hope National Medical Center
Duarte, California, United States
Palo Alto Medical Foundation
Fremont, California, United States
VA Central California Health Care System
Fresno, California, United States
Sharp Memorial Hospital
La Mesa, California, United States
Palo Alto Medical Foundation
Mountain View, California, United States
Palo Alto Medical Foundation
Palo Alto, California, United States
University of California San Diego - Moores Cancer Center
San Diego, California, United States
Sharp Memorial Hospital
San Diego, California, United States
University of California San Francisco
San Francisco, California, United States
Palo Alto Medical Foundation
Santa Cruz, California, United States
Adventist Health St. Helena/St. Helena Hospital/Martin O'Neil Cancer Center
St. Helena, California, United States
Palo Alto Medical Foundation
Sunnyvale, California, United States
Georgetown University Medical Center
Washington D.C., District of Columbia, United States
MedStar Washington Hospital Center
Washington D.C., District of Columbia, United States
University of Hawaii Cancer Center
Honolulu, Hawaii, United States
Pali Momi Medical Center
‘Aiea, Hawaii, United States
Rush University Medical Center
Chicago, Illinois, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
Northshore University Health System
Evanston, Illinois, United States
Loyola University
Maywood, Illinois, United States
Quincy Medical Group
Quincy, Illinois, United States
Carle Cancer Center
Urbana, Illinois, United States
Cancer Center of Kansas
Wichita, Kansas, United States
Eastern Maine Medical Center
Brewer, Maine, United States
New England Cancer Specialists
Kennebunk, Maine, United States
New England Cancer Specialists
Scarborough, Maine, United States
New England Cancer Specialists
Topsham, Maine, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Dana Farber Cancer Institute
Milford, Massachusetts, United States
Dana Farber Cancer Institute
South Weymouth, Massachusetts, United States
University of Minnesota
Minneapolis, Minnesota, United States
Metro Minnesota Community Oncology Research Consortium
Saint Louis Park, Minnesota, United States
Washington University School of Medicine
St Louis, Missouri, United States
Nebraska Methodist Hospital
Omaha, Nebraska, United States
Nevada Cancer Research Foundation
Las Vegas, Nevada, United States
New Hampshire Oncology & Hematology
Concord, New Hampshire, United States
New Hampshire Oncology & Hematology
Hooksett, New Hampshire, United States
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, United States
Memorial Sloan Kettering Cancer Center
Middletown, New Jersey, United States
Atlantic Health System/Morristown Medical Center
Morristown, New Jersey, United States
New Mexico Oncology Hematology Consultants
Albuquerque, New Mexico, United States
University of New Mexico Comprehensive Cancer Center
Albuquerque, New Mexico, United States
Memorial Medical Center- Cancer Center
Las Cruces, New Mexico, United States
Christus St. Vincent's Regional Cancer Center
Santa Fe, New Mexico, United States
VA Western New York
Buffalo, New York, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
Memorial Sloan Kettering Cancer Center
Commack, New York, United States
Memorial Sloan Kettering Cancer Center
Harrison, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Weill Cornell Medical Ctr - New York Presbyterian Hospital
New York, New York, United States
Montefiore Medical Center
New York, New York, United States
SUNY Upstate Medical University
Syracuse, New York, United States
University of North Carolina Hospital
Chapel Hill, North Carolina, United States
Novant Health Presbyterian Medical Center
Charlotte, North Carolina, United States
VA Salisbury
Salisbury, North Carolina, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States
Dayton Physicians Miami Valley South
Centerville, Ohio, United States
The Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
The Toledo Clinic
Toledo, Ohio, United States
Oklahoma Cancer Specialists and Research Institute
Tulsa, Oklahoma, United States
Providence Portland Medical Center
Portland, Oregon, United States
Oregon Health & Science University
Portland, Oregon, United States
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States
Spartanburg Medical Center/Gibbs Cancer Center
Spartanburg, South Carolina, United States
University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Marshfield Clinic Cancer Center
Marshfield, Wisconsin, United States
Froedtert Hospital/Medical College of Wisconsin
Milwaukee, Wisconsin, United States
Countries
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References
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Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015 Jan-Feb;65(1):5-29. doi: 10.3322/caac.21254. Epub 2015 Jan 5.
Zietman AL, Chung CS, Coen JJ, Shipley WU. 10-year outcome for men with localized prostate cancer treated with external radiation therapy: results of a cohort study. J Urol. 2004 Jan;171(1):210-4. doi: 10.1097/01.ju.0000100980.13364.a6.
Humphrey PA, Moch H, Cubilla AL, Ulbright TM, Reuter VE. The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part B: Prostate and Bladder Tumours. Eur Urol. 2016 Jul;70(1):106-119. doi: 10.1016/j.eururo.2016.02.028. Epub 2016 Mar 17.
Zelefsky MJ, Ben-Porat L, Scher HI, Chan HM, Fearn PA, Fuks ZY, Leibel SA, Venkatraman ES. Outcome predictors for the increasing PSA state after definitive external-beam radiotherapy for prostate cancer. J Clin Oncol. 2005 Feb 1;23(4):826-31. doi: 10.1200/JCO.2005.02.111.
Qu Y, Dai B, Ye D, Kong Y, Chang K, Jia Z, Yang X, Zhang H, Zhu Y, Shi G. Constitutively active AR-V7 plays an essential role in the development and progression of castration-resistant prostate cancer. Sci Rep. 2015 Jan 7;5:7654. doi: 10.1038/srep07654.
Gershon RC, Rothrock N, Hanrahan R, Bass M, Cella D. The use of PROMIS and assessment center to deliver patient-reported outcome measures in clinical research. J Appl Meas. 2010;11(3):304-14.
Aggarwal R, Heller G, Hillman DW, Xiao H, Picus J, Taplin ME, Dorff T, Appleman L, Weckstein D, Patnaik A, Bryce A, Shevrin D, Mohler J, Anderson D, Rao A, Tagawa S, Tan A, Halabi S, Dooley K, O'Brien P, Chen R, Ryan CJ, Eggener SE, Morris MJ; EORTC-55994 Study Group. PRESTO: A Phase III, Open-Label Study of Intensification of Androgen Blockade in Patients With High-Risk Biochemically Relapsed Castration-Sensitive Prostate Cancer (AFT-19). J Clin Oncol. 2024 Apr 1;42(10):1114-1123. doi: 10.1200/JCO.23.01157. Epub 2024 Jan 23.
Other Identifiers
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AFT-19
Identifier Type: -
Identifier Source: org_study_id