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

NCT03009981 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: AFT-19
• Study Type: interventional
• Target: 504
• Locations: 1 country
• Sites: 69

Brief 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.

Conditions

Prostate Cancer

Keywords

PSA; Degarelix; Apalutamide; Abiraterone Acetate; Radical Prostatectomy; Bicalutamide; Leuprolide; Lupron

Outcome Measures

Primary Outcomes (1)

• PSA progression-free survival in the intent-to-treat population

  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 Outcomes (12)

• PSA progression-free survival in the testosterone-evaluable population

  36 months

• PSA progression-free survival in both the intent-to-treat and testosterone-evaluable populations

  36 months

• Serum testosterone

  12 months

• Time to castration resistance

  6 years

• Metastasis-Free Survival

  6 years

Study Arms (3)

Arm A: Degarelix Monotherapy OR Leuprolide/Bicalutamide

ACTIVE COMPARATOR

Patients will receive degarelix OR leuprolide with bicalutamide.

Drug: LHRH Analogue

Arm B: Degarelix/Apalutamide

EXPERIMENTAL

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: Apalutamide; Drug: LHRH Analogue

Arm C: Degarelix/Apalutamide/Abiraterone/Prednisone

EXPERIMENTAL

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: Apalutamide; Drug: LHRH Analogue; Drug: Abiraterone Acetate; Drug: Prednisone

Interventions

Apalutamide DRUG

Take apalutamide 240 mg (four 60 mg tablets) orally once daily, starting on C1D1 and continuing throughout 52-week treatment period.

Also known as: Erleada

Arm B: Degarelix/Apalutamide; Arm C: Degarelix/Apalutamide/Abiraterone/Prednisone

LHRH Analogue DRUG

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.

Also known as: Degarelix (Firmagon), Leuprolide (Lupron) and Bicalutamide

Arm A: Degarelix Monotherapy OR Leuprolide/Bicalutamide; Arm B: Degarelix/Apalutamide; Arm C: Degarelix/Apalutamide/Abiraterone/Prednisone

Abiraterone Acetate DRUG

Take abiraterone acetate 1000 mg (four 250 mg tablets) orally once daily, starting on C1D1 and continuing throughout 52-week treatment period.

Also known as: Zytiga

Arm C: Degarelix/Apalutamide/Abiraterone/Prednisone

Prednisone DRUG

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.

Also known as: Deltasone

Arm C: Degarelix/Apalutamide/Abiraterone/Prednisone

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: collaborator
• Alliance Foundation Trials, LLC.: lead

Study Sites (69)

The Mayo Clinic - Phoenix

Phoenix, Arizona, 85054, United States

Location

Sharp Memorial Hospital

Chula Vista, California, 91911, United States

Location

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

Palo Alto Medical Foundation

Fremont, California, 94538, United States

Location

VA Central California Health Care System

Fresno, California, 93703, United States

Location

Sharp Memorial Hospital

La Mesa, California, 91942, United States

Location

Palo Alto Medical Foundation

Mountain View, California, 94040, United States

Location

Palo Alto Medical Foundation

Palo Alto, California, 94301, United States

Location

University of California San Diego - Moores Cancer Center

San Diego, California, 92093, United States

Location

Sharp Memorial Hospital

San Diego, California, 92123, United States

Location

University of California San Francisco

San Francisco, California, 94158, United States

Location

Palo Alto Medical Foundation

Santa Cruz, California, 95065, United States

Location

Adventist Health St. Helena/St. Helena Hospital/Martin O'Neil Cancer Center

St. Helena, California, 94574, United States

Location

Palo Alto Medical Foundation

Sunnyvale, California, 94086, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

MedStar Washington Hospital Center

Washington D.C., District of Columbia, 20007, United States

Location

University of Hawaii Cancer Center

Honolulu, Hawaii, 96813, United States

Location

Pali Momi Medical Center

‘Aiea, Hawaii, 96701, United States

Location

Rush University Medical Center

Chicago, Illinois, 606012, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Northshore University Health System

Evanston, Illinois, 60201, United States

Location

Loyola University

Maywood, Illinois, 60153, United States

Location

Quincy Medical Group

Quincy, Illinois, 62301, United States

Location

Carle Cancer Center

Urbana, Illinois, 61801, United States

Location

Cancer Center of Kansas

Wichita, Kansas, 67214, United States

Location

Eastern Maine Medical Center

Brewer, Maine, 04412, United States

Location

New England Cancer Specialists

Kennebunk, Maine, 04043, United States

Location

New England Cancer Specialists

Scarborough, Maine, 04074, United States

Location

New England Cancer Specialists

Topsham, Maine, 04086, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute

Milford, Massachusetts, 01757, United States

Location

Dana Farber Cancer Institute

South Weymouth, Massachusetts, 02190, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Metro Minnesota Community Oncology Research Consortium

Saint Louis Park, Minnesota, 55416, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Nebraska Methodist Hospital

Omaha, Nebraska, 68114, United States

Location

Nevada Cancer Research Foundation

Las Vegas, Nevada, 89106, United States

Location

New Hampshire Oncology & Hematology

Concord, New Hampshire, 03301, United States

Location

New Hampshire Oncology & Hematology

Hooksett, New Hampshire, 03106, United States

Location

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Cancer Center

Middletown, New Jersey, 07748, United States

Location

Atlantic Health System/Morristown Medical Center

Morristown, New Jersey, 07962, United States

Location

New Mexico Oncology Hematology Consultants

Albuquerque, New Mexico, 87109, United States

Location

University of New Mexico Comprehensive Cancer Center

Albuquerque, New Mexico, 87131, United States

Location

Memorial Medical Center- Cancer Center

Las Cruces, New Mexico, 88011, United States

Location

Christus St. Vincent's Regional Cancer Center

Santa Fe, New Mexico, 87505, United States

Location

VA Western New York

Buffalo, New York, 14215, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Memorial Sloan Kettering Cancer Center

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Cancer Center

Harrison, New York, 11533, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Weill Cornell Medical Ctr - New York Presbyterian Hospital

New York, New York, 10065, United States

Location

Montefiore Medical Center

New York, New York, 10461, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

University of North Carolina Hospital

Chapel Hill, North Carolina, 27514, United States

Location

Novant Health Presbyterian Medical Center

Charlotte, North Carolina, 28204, United States

Location

VA Salisbury

Salisbury, North Carolina, 28144, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Dayton Physicians Miami Valley South

Centerville, Ohio, 45459, United States

Location

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

The Toledo Clinic

Toledo, Ohio, 43623, United States

Location

Oklahoma Cancer Specialists and Research Institute

Tulsa, Oklahoma, 74146, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Spartanburg Medical Center/Gibbs Cancer Center

Spartanburg, South Carolina, 29303, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Marshfield Clinic Cancer Center

Marshfield, Wisconsin, 54449, United States

Location

Froedtert Hospital/Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (8)

• 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.

  PMID: 25559415 BACKGROUND

• 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.

  PMID: 14665878 BACKGROUND

• 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.

  PMID: 26996659 BACKGROUND

• 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.

  PMID: 15681527 BACKGROUND

• 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.

  PMID: 25563505 BACKGROUND

• 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.

  PMID: 20847477 BACKGROUND

• Morgan TM, Boorjian SA, Buyyounouski MK, Chapin BF, Chen DYT, Cheng HH, Chou R, Jacene HA, Kamran SC, Kim SK, Kirkby E, Luckenbaugh AN, Nathanson BJ, Nyame YA, Posadas EM, Tran PT, Chen RC. Salvage Therapy for Prostate Cancer: AUA/ASTRO/SUO Guideline Part III: Salvage Therapy After Radiotherapy or Focal Therapy, Pelvic Nodal Recurrence and Oligometastasis, and Future Directions. J Urol. 2024 Apr;211(4):526-532. doi: 10.1097/JU.0000000000003890. Epub 2024 Feb 29.

  PMID: 38421252 DERIVED

• 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.

  PMID: 38261983 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

apalutamide; Gonadotropin-Releasing Hormone; acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide; Leuprolide; bicalutamide; Abiraterone Acetate; Prednisone

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes

Study Officials

• Evanthia Evanthia Galanis, MD

  Alliance Foundation Trials, LLC.

  PRINCIPAL INVESTIGATOR

• Rahul Aggarwal, MD

  University of California, San Francisco

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2017
• First Posted: January 4, 2017
• Study Start: March 6, 2017
• Primary Completion: June 25, 2025
• Study Completion: June 25, 2025
• Last Updated: December 18, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (69)