Radiation Therapy and Androgen Deprivation Therapy with or without Abiraterone Acetate and Apalutamide in Treating Patients with Prostate Cancer

Status: Active

Description

This randomized phase II trial studies how well radiation therapy and androgen deprivation therapy (ADT) works when given together with apalutamide and abiraterone acetate in treating patients with prostate cancer. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. ADT blocks the function of hormones including testosterone which prostate cancer uses to grow and spread. Abiraterone acetate and apalutamide may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving radiation therapy and ADT with apalutamide and abiraterone acetate may work better in treating patients with prostate cancer.

Eligibility Criteria

Inclusion Criteria

  • Histologically confirmed prostate cancer
  • PSA >= 0.1 after radical prostatectomy (value w/in 90 days of registration and prior to initiating any ADT) AND at least 1 unfavorable risk factor listed below * Gleason 8-10 * PSA > 0.5 * Pathologically or imaging positive lymph nodes * pT3 or pT4 * PSA doubling time (DT) < 10 months * Negative margins * Persistent PSA after radical prostatectomy (RP) (PSA never dropped below 0.1 after RP) * Local/regional recurrence on imaging * Decipher “high risk” (a Medicare-reimbursed test for risk of metastases after prostatectomy)
  • Candidate for salvage radiation and ADT treatment
  • Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information prior to registration; NOTE: HIPAA authorization may be included in the informed consent or obtained separately; subject must have the ability to understand and willingness to sign the written informed consent document
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Platelet count (plt) >= 100,000/uL (within 90 days of registration)
  • Hemoglobin (Hgb) >= 9 g/dL (within 90 days of registration)
  • Absolute neutrophil count (ANC) >= 1000 cells/uL (within 90 days of registration)
  • Creatinine clearance >= 45 mL/min; Cockcroft-Gault formula will be used to calculate creatinine clearance (within 90 days of registration)
  • Bilirubin =< 1.5 x upper limit of normal (ULN); in subjects with Gilbert’s syndrome, if total bilirubin is > 1.5 x ULN, measure direct and indirect bilirubin; if direct bilirubin is =< 1.5 x ULN, subject may be eligible (within 90 days of registration)
  • Aspartate aminotransferase (AST) =< 2.5 x ULN (within 90 days of registration)
  • Alanine aminotransferase (ALT) =< 2.5 x ULN (within 90 days of registration)
  • Serum albumin > 3.0 g/dL (within 90 days of registration)
  • Serum potassium >= 3.5 mmol/L (within 90 days of registration)
  • International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN (unless on prophylactic or therapeutic dosing with low molecular weight heparin) (within 90 days of registration)
  • Activated partial thromboplastin time (aPTT) =< 1.5 x ULN (unless on prophylactic or therapeutic dosing with low molecular weight heparin) (within 90 days of registration)
  • 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
  • Ability to understand and comply with study procedures for the entire length of the study as determined by the site investigator or protocol designee
  • Medications known to lower the seizure threshold must be discontinued or substituted prior to cycle 1 day 1 (C1D1) of study treatment for patients on Arm 2
  • Use of CYP3A4 inhibitors or inducers and CYP2D6 substrates must be taken with caution for patients on Arm 2
  • Able to swallow pills

Exclusion Criteria

  • Post-prostatectomy use of ADT for > 30 days prior to study entry (ADT defined as the use of a GnRH agonist, with or without an anti-androgen)
  • Prior pelvic radiation is not allowed, unless additional radiation can be safely delivered according to the treating investigator
  • PSA > 15 ng/mL in screening
  • History of any of the following: * Seizure or known condition that may predispose to seizure (e.g., prior stroke within 1 year of randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign central nervous system [CNS] or meningeal disease which may require treatment with surgery or radiation therapy) * Severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 6 months prior to randomization
  • Current evidence of any of the following: * Uncontrolled hypertension * Gastrointestinal disorder affecting absorption * Active infection (e.g., human immunodeficiency virus [HIV] or viral hepatitis) * Any chronic medical condition requiring a dose of corticosteroid higher than 10 mg prednisone/prednisolone once daily * Any condition that, in the opinion of the site investigator, would preclude participation in this study * Moderate or severe hepatic impairment (Child Pugh class B or C)
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to study drugs
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, psychiatric illness or social situations that would limit compliance with study requirements
  • Individuals with a history of another malignancy are not eligible if: * The cancer is under active treatment or * The cancer can be seen on radiology scans or * If they are off cancer treatment but in the opinion of their oncologist have a high risk of relapse within 5 years
  • Confirmed bone metastases on imaging

Locations & Contacts

California

San Diego
University of California San Diego
Status: Active
Contact: Brent Shane Rose
Email: Bsrose@ucsd.edu
San Francisco
UCSF Medical Center-Mount Zion
Status: Approved
Contact: Anthony C. Wong
Phone: 415-514-2070
Email: Anthony.Wong2@ucsf.edu

Connecticut

New Haven
Yale University
Status: Active
Contact: James Byunghoon Yu
Phone: 203-785-5703
Email: James.b.yu@yale.edu

Illinois

Chicago
University of Chicago Comprehensive Cancer Center
Status: Active
Contact: Russell Zelig Szmulewitz
Email: Rszmulew@medicine.bsd.uchicago.edu
New Lenox
UC Comprehensive Cancer Center at Silver Cross
Status: Active
Contact: Russell Zelig Szmulewitz
Email: Rszmulew@medicine.bsd.uchicago.edu
Orland Park
University of Chicago Medicine-Orland Park
Status: Active
Contact: Russell Zelig Szmulewitz
Email: Rszmulew@medicine.bsd.uchicago.edu

Massachusetts

Boston
Beth Israel Deaconess Medical Center
Status: Active
Contact: Glenn J. Bubley
Email: gbubley@bidmc.harvard.edu
Brigham and Women's Hospital
Status: Active
Contact: Paul L. Nguyen
Email: PNGUYEN1@PARTNERS.ORG
Dana-Farber Cancer Institute
Status: Active
Contact: Paul L. Nguyen
Email: PNGUYEN1@PARTNERS.ORG
Milford
Dana-Farber / Brigham and Women's Cancer Center at Milford Regional
Status: Active
Contact: Peter F. Orio
Email: porio@lroc.harvard.edu
South Weymouth
Dana-Farber / Brigham and Women's Cancer Center at South Shore
Status: Active
Contact: Peter F. Orio
Email: porio@lroc.harvard.edu

Michigan

Ann Arbor
University of Michigan Comprehensive Cancer Center
Status: Active
Contact: Daniel Eidelberg Spratt
Email: Sprattda@med.umich.edu
Brighton
University of Michigan - Brighton Center for Specialty Care
Status: Active
Contact: Daniel Eidelberg Spratt
Email: Sprattda@med.umich.edu

New Jersey

Basking Ridge
Memorial Sloan Kettering Basking Ridge
Status: Active
Contact: Marisa Ariane Kollmeier
Email: KollmeiM@mskcc.org
Middletown
Memorial Sloan Kettering Monmouth
Status: Active
Contact: Marisa Ariane Kollmeier
Email: KollmeiM@mskcc.org
Montvale
Memorial Sloan Kettering Bergen
Status: Active
Contact: Marisa Ariane Kollmeier
Email: KollmeiM@mskcc.org

New York

Commack
Memorial Sloan Kettering Commack
Status: Active
Contact: Marisa Ariane Kollmeier
Email: KollmeiM@mskcc.org
Hauppauge
Memorial Sloan Kettering Skin Cancer Center
Status: Active
Contact: Marisa Ariane Kollmeier
Email: KollmeiM@mskcc.org
New York
Memorial Sloan Kettering Cancer Center
Status: Active
Contact: Marisa Ariane Kollmeier
Email: KollmeiM@mskcc.org
Uniondale
Memorial Sloan Kettering Nassau
Status: Active
Contact: Marisa Ariane Kollmeier
Email: KollmeiM@mskcc.org
West Harrison
Memorial Sloan Kettering Westchester
Status: Active
Contact: Marisa Ariane Kollmeier
Email: KollmeiM@mskcc.org

Texas

Houston
M D Anderson Cancer Center
Status: Active
Contact: Karen E. Hoffman
Email: KHoffman1@mdanderson.org

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To evaluate the difference in prostate surface antigen (PSA) progression-free survival between the arms of the trial.

SECONDARY OBJECTIVES:

I. To evaluate metastasis-free survival.

II. To evaluate cause-specific survival (prostate cancer, and other causes).

III. To evaluate overall survival.

IV. To evaluate time to testosterone recovery.

V. To describe toxicity as measured by Common Terminology Criteria for Adverse Events (CTCAE) version (v).4.

VI. To report on patient-reported quality of life.

VII. To describe cardiovascular events.

VIII. To evaluate time to re-initiation of ADT.

CORRELATIVE/EXPLORATORY OBJECTIVES:

I. Discovery of genetic predictors of the primary and secondary endpoints listed above.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive gonadotropin-releasing hormone analog via injection monthly or every 3 months for 6 months. Patients also receive bicalutamide orally (PO) once daily (QD) on day 1. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Within 4-10 weeks of ADT, patients undergo radiation therapy for 8 weeks.

ARM II: Patients receive gonadotropin-releasing hormone analog via injection monthly or every 3 months for 6 months. Patients also receive abiraterone acetate PO QD, prednisone PO twice daily (BID), and apalutamide PO QD on days 1-28. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Within 4-10 weeks of ADT, patients undergo radiation therapy.

After completion of study treatment, patients are followed up every 6 months for 5 years, and then periodically thereafter.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Dana-Farber Harvard Cancer Center

Principal Investigator
Paul L. Nguyen

Trial IDs

Primary ID 16-623
Secondary IDs NCI-2017-02329
Clinicaltrials.gov ID NCT03141671