Combination Drugs for Treating Metastatic Castration-Resistant Prostate Cancer with Tumor Mutation that Affect DNA Repair

About the Study

The goal of this study is to compare the effectiveness of three different drug combinations to treat men with metastatic castration-resistant prostate cancer (mCRPR), who also have a mutation in a gene that affects DNA repair found through tumor testing. 

Type of Study

This is a randomized, open-label study. In a randomized study, participants are placed into one of the two study groups by chance. Neither patients nor their research doctor choose the group into which the participants are placed. In an open-label study, all patients will know which intervention or medication they are receiving during the study.

What the Study Involves

Participants will be assigned to one of four groups. All groups will receive their treatment in 28 day cycles.

• Groups 1, 2, and 3 will consist only of men with tumors containing mutations in ATM, BRCA1, or BRCA2 genes. Participants with a tumor mutation in one of these genes will be randomly assigned to one of these 3 groups
  • Group 1 will receive oral Abiraterone (once) + Prednisone (twice) daily
  • Group 2 will receive oral olaparib twice daily
  • Group 3 will receive oral Abiraterone (once) + Prednisone (twice) + Olaparib (twice) daily.
• Group 4 will have participants with tumors containing mutations in FANCA, PALB2, RAD51, ERCC3, MRE11, NBN, MLH3, CDK12, CHEK2, HDAC2, ATR, PMS2, GEN1, MSH2, MSH6, BRIP1, or FAM175A.
  • Group 4 will receive oral olaparib twice daily in 28 day cycles

Participants in single treatment groups may cross over to opposite single treatment groups if their tumor grows/disease progresses. Overall, the study goal is to determine whether the prostate cancer grows or not after treatment. Participants will be followed for up to 2 years.

Study Sites

California

• Los Angeles
  University of California Los Angeles
  Contact: Matthew Rettig, MD    310-268-3622          

Florida

• Tampa
  Moffitt Cancer Center and Research Institute
  Contact: Jingsong Zhang, MD    813-745-4673      

Illinois

• Chicago
  Northwestern Medicine
  Contact: Maha Hussain, MD    312-695-6180
• Chicago
  Rush University Cancer Center
  Contact: Nicklas Pfanzelter, MD    312-942-5904
• Chicago
  University of Chicago      
  Contact: Russell Szmulewitz, MD    773-702-7609
• Evanston      
  Kellogg Cancer Center - NorthShore University
  Contact: Daniel Shevrin, MD    847-570-2515      

Indiana

• Indianapolis
  Indiana University/ Melvin and Bren Simon Cancer Center
  Contact: Roberto Pili, MD    317-948-8310      

Maryland

• Baltimore
  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  Contact: Emmanuel Antonarakis, MD    410-502-7528             

Michigan

• Ann Arbor
  University of Michigan Health System Recruiting
  Contact: Todd Morgan, M.D.    734-647-8903        

Minnesota

• Rochester
  Mayo Clinic
• Contact: Manish Kohli, M.D.    507-538-3270           

Missouri

• Saint Louis
  Washington University School of Medicine
  Contact: Joel Picus, MD    314-747-9281      

New York

• New York
  Weill Cornell Medical College
  Contact: Himisha Beltran, MD    646-962-2072       

North Carolina

• Chapel Hill
  University of North Carolina at Chapel Hill
  Contact: Young Whang, MD    919-966-4996         

Utah

• Salt Lake City
  Huntsman Cancer Institute - University of Utah
  Contact: Neeraj Agarwal, MD    801-585-0100      

Virginia

• Charlottesville
  University of Virginia
  Contact: Robert Dreicer, MD    434-924-9333      

Men 18 years or older may participate if they meet the following: 

• Have a diagnosis of metastatic castration-resistant prostate cancer.
• Have a tumor mutation in one of the following genes: ATM, BRCA1, BRCA2, FANCA, PALB2, RAD51, ERCC3, MRE11, NBN, MLH3, CDK12, CHEK2, HDAC2, ATR, PMS2, GEN1, MSH2, MSH6, BRIP1, or FAM175A

Men may not participate if they have the following:

• prior treatment with other PARP inhibitors 
• prior treatment with chemotherapy for hormone resistant disease
• other investigational treatments for metastatic hormone resistant prostate cancer
• an active second cancer
• history of seizures or cancer spread to the brain 
• history of a heart condition
• had a bone marrow transplant 
• must not take CYP3A4 inhibitors
• must not have brain metastases