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

Status: Active

Description

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.

Eligibility Criteria

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

Locations & Contacts

Arizona

Scottsdale
Mayo Clinic in Arizona
Status: Active
Name Not Available

California

Duarte
City of Hope Comprehensive Cancer Center
Status: Active
Name Not Available
Fresno
VA Central California Fresno Medical Center
Status: Active
Contact: Laura B Schubert
Phone: 559-225-6100ext5610
Email: laura.schubert@va.gov
San Diego
University of California San Diego
Status: Active
Name Not Available
San Francisco
UCSF Medical Center-Mount Zion
Status: Active
Name Not Available

Hawaii

Aiea
Pali Momi Medical Center
Status: Active
Name Not Available
Honolulu
Straub Clinic and Hospital
Status: Active
Name Not Available

Illinois

Chicago
University of Chicago Comprehensive Cancer Center
Status: Active
Name Not Available

Maryland

Baltimore
University of Maryland / Greenebaum Cancer Center
Status: Active
Contact: Michele Ann Besche
Phone: 410-328-8610
Email: mbesche@umm.edu

Massachusetts

Boston
Brigham and Women's Hospital
Status: Active
Name Not Available
Dana-Farber Cancer Institute
Status: Active
Name Not Available
Milford
Dana-Farber / Brigham and Women's Cancer Center at Milford Regional
Status: Active
Name Not Available
South Weymouth
Dana-Farber / Brigham and Women's Cancer Center at South Shore
Status: Active
Name Not Available

Minnesota

Minneapolis
University of Minnesota / Masonic Cancer Center
Status: Active
Name Not Available

Missouri

Saint Louis
Siteman Cancer Center at Washington University
Status: Active
Name Not Available

New Mexico

Albuquerque
New Mexico Oncology Hematology Consultants
Status: Active
Name Not Available
University of New Mexico Cancer Center
Status: Active
Name Not Available
Las Cruces
Memorial Medical Center - Las Cruces
Status: Active
Name Not Available
Santa Fe
Christus Saint Vincent Regional Cancer Center
Status: Active
Name Not Available

New York

Buffalo
Roswell Park Cancer Institute
Status: Active
Name Not Available
New York
Memorial Sloan Kettering Cancer Center
Status: Active
Name Not Available

North Carolina

Chapel Hill
UNC Lineberger Comprehensive Cancer Center
Status: Active
Name Not Available
Winston-Salem
Wake Forest University Health Sciences
Status: Active
Name Not Available

Ohio

Columbus
Ohio State University Comprehensive Cancer Center
Status: Active
Name Not Available

Oregon

Portland
OHSU Knight Cancer Institute
Status: Active
Name Not Available

Pennsylvania

Pittsburgh
University of Pittsburgh Cancer Institute (UPCI)
Status: Active
Name Not Available

Texas

Houston
M D Anderson Cancer Center
Status: Active
Name Not Available

Trial Objectives and Outline

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.

Trial Phase & Type

Trial Phase

Phase III

Trial Type

Treatment

Lead Organization

Lead Organization
Alliance Foundation Trials, LLC.

Trial IDs

Primary ID AFT-19
Secondary IDs NCI-2017-01471
Clinicaltrials.gov ID NCT03009981