Abiraterone/Prednisone, Olaparib, or Abiraterone/Prednisone + Olaparib in Patients With Metastatic Castration-Resistant Prostate Cancer With DNA Repair Defects

About the Study

This is a phase II study looking at different treatment combinations for men with metastatic, castration resistant prostate cancer (mCRPC) to see which is most effective for improving progression free survival (keeping the cancer from progressing). The study will include testing for genes within the tumor to determine eligibility for the study. 

The study multiple treatment arms. Patients with tumors that have ATM, BRCA1 and/or BRCA2 mutations or defects will be randomly assigned to one of the treatment arms of the study. Patients with tumors that have mutations in other DNA repair genes including FANCA, PALB2, RAD51, ERCC3, MRE11, NBN, MLH3, CDK12, CHEK2, HDAC2, ATR, PMS2, GEN1, MSH2, MSH6, BRIP1, or FAM175A will be assigned to Arm IV with single agent olaparib.

Type of Study

This is a randomized, open-label, 4-arm study. This study allows crossover. 

• The study has four arms. This means that patients in the study are placed in one of four different groups. 
• This is a randomized study for men with an ATM, BRCA1 and/or BRCA2 mutation or defect within their tumor. Men with these defects will be randomized to one of three separate treatment arms:
  • Active Comparator: Arm I: Abiraterone + Prednisone
  • Active Comparator: Arm II: Olaparib
  • Active Comparator: Arm III: Abiraterone + Prednisone + Olaparib
• Men whose tumors have a mutation in another DNA repair genes including FANCA, PALB2, RAD51, ERCC3, MRE11, NBN, MLH3, CDK12, CHEK2, HDAC2, ATR, PMS2, GEN1, MSH2, MSH6, BRIP1, or FAM175A will not be randomized but will be assigned to Arm IV with single agent olaparib.
• The study is open-label. All participating patients will know which group they have been assigned to and what treatment they are receiving. There is no placebo in this study.
• The study allows crossover. This means that patients who progress on the abiraterone arm will be given the opportunity to crossover into the olaparib arm if they choose. Patients who progress while on the olaparib arm will be given the opportunity to crossover into the abiraterone arm if they choose. 

What the Study Entails

• Patients with documented metastatic castration resistant prostate cancer must:
  • undergo a biopsy, or
  • have metastatic tumor tissue from prior metastatic disease biopsy, or
  • for patients with an inherited (germline) mutation in BRCA1, BRCA2, ATM or other known DNA-repair genes, these patients are not required to undergo a biopsy to participate, however,it is preferred that these patients also undergo a metastatic disease biopsy to better define the scope of the DNA repair defects in their metastatic tumor
• Patients with tumors that have ATM, BRCA1 and/or BRCA2 mutations/deletions/loss of heterozygosity will be randomized in a 1:1:1 fashion to one of the three following arms:
  • Arm I: Abiraterone + Prednisone
    • Abiraterone 1000 mg orally once daily and prednisone 5 mg orally twice daily, days 1-28 in 28 day cycles.
  • Arm II: Olaparib
    • Olaparib 300 mg orally twice daily for days 1-28 in 28 day cycles.
  • Arm III: Abiraterone + Prednisone + Olaparib
    • Abiraterone 1000 mg orally once daily, prednisone 5 mg orally twice daily, olaparib 300 mg orally twice daily for days 1-28 in 28 day cycles.
• Patients with mutations in other DNA repair genes including FANCA, PALB2, RAD51, ERCC3, MRE11, NBN, MLH3, CDK12, CHEK2, HDAC2, ATR, PMS2, GEN1, MSH2, MSH6, BRIP1, or FAM175A defects will be assigned to Arm IV with single agent olaparib.
  • Arm IV Olaparib
    • Olaparib 300 mg orally twice daily for days 1-28 in 28 day cycles.

Study Sites

• Florida
  • Tampa, FL
    • Moffitt Cancer Center: Contact Jingsong Zhang, MD    813-745-4673  
• Illinois
  • Chicago, IL
    • Northwestern Medicine: Contact Maha Hussain 312-695-6180      
  • Chicago, IL
    • Rush University Cancer Center: Contact Nicklas Pfanzelter, MD 312-942-5904 
  • Chicago, IL
    •  University of Chicago: Contact Russell Szmulewitz, MD  773-702-7609  
  • Evanston, IL
    • Kellog Cancer Center, NorthShore University: Contact Daniel Shevrin, MD  847-570-2515 
• Indiana
  • Indianapolis, IN
    • Indiana University/ Melvin and Bren Simon Cancer Center: Contact Roberto Pili, MD    317-948-8310
• Maryland
  • Baltimore, MD
    • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: Contact Emmanuel Antonarakis, MD 410-502-7528 
• Michigan
  • Ann Arbor, MI
    • University of Michigan Health System: Contact Todd Morgan, MD 734-647-8903 
  • Detroit, MI
    •  Karmanos Cancer Center: Contact Ulka Vaishampayan, MD 313-745-5111 
• Minnesota
  • Rochester, MN
    • Mayo Clinic: Contact Manish Kohli, MD 507-538-3270  
• Missouri
  • St. Louis, MO
    • Washington University School of Medicine: Contact Joel Picus, MD 314-747-9281 
• New York
  • New York, NY
    • Weill Cornell Medical Center: Contact: Himisha Beltran, MD 646-962-2072  
• North Carolina
  • Chapel Hill, NC
    • University of North Carolina, Chapel Hill: Contact Young Whang, MD 919-966-4996 
• Utah
  • Salt Lake City, UT
    • Huntsman Cancer Center: Contact Neeraj Agarwal, MD 801-585-0100 
• Virginia
  • Charlottesville, VA
    • University of Virginia: Contact Robert Dreicer, MD  434-924-9333 

Principal Investigator

Maha Hussain at Northwestern University: 312-695-6180