A Phase 2 Study of Olaparib Monotherapy in Metastatic Breast Cancer Patients with Germline or Somatic Mutations in DNA Repair Genes (Olaparib Expanded)

 About the Study

DFCI 17-428 (Olaparib Expanded) is a study looking at whether the drug Olaparib is effective treatment for people with certain types of metastatic breast cancer. Olaparib belongs to a class of drugs known as PARP inhibitors. PARP inhibitors are particularly effective for treating tumors in people with an inherited BRCA mutation. This study is looking at whether olaparib is also effective for treating metastatic breast cancer in people who do not have an inherited BRCA mutation.

The study is looking at olaparib to treat metastatic breast cancer in two specific groups of patients who have tested negative for a BRCA mutation:

• People with metastatic breast cancer whose tumor has a somatic mutation in BRCA1 or BRCA2. This means that although the patient does not have an inherited BRCA mutation, their tumor cells have developed mutations in either of these genes.
• Patients with an inherited mutation or tumor mutation in PALB2.

Type of Study

This is a Phase 2, non-randomized 2-arm, open-label study evaluating olaparib in metastatic breast cancer patients with either a non-BRCA germline (inherited) mutation or a somatic (acquired) mutation found in the blood or tumor tissue. Participants with a BRCA1 or BRCA2 germline mutation are not eligible for this study, as Olaparib is already FDA approved for these patients. Response to treatment will be analyzed by periodic assessments of the tumor by CT scans.

• The study is non-randomized, meaning that all patients will receive the drug, olaparib. The study has two arms:
  • Cohort 1 is open to patients with a germline (inherited) mutation in one of the DNA repair genes that is associated with breast cancer, other than BRCA1 and BRCA2.
  • Cohort 2 is open to patients with a somatic mutation (mutation in their tumor) in BRCA1 or BRCA2 or one of the other DNA repair genes that is associated with breast cancer.

What the Study Entails

• Metastatic breast cancer patients (women or men) will qualify for the study provided they have a mutation in one of the DNA repair genes described above
• Study participants will take Olaparib, a tablet medication, by mouth. The oral dose of olaparib will be taken 2 times per day, 12 hours apart with food.
• Each study treatment cycle lasts 21 days (3 weeks)
• Treatment will continue until you are no longer benefitting from the treatment (disease progression), you experience intolerable side effects or you decide you no longer wish to participate
• A biopsy for research purposes is required prior to the start of treatment on this study
• A follow-up visit will occur 30 days after you come off treatment to assess any side effects of the study drug
• Participants will be monitored every 6 weeks for the first 24 weeks for assessment of disease and then every 12 weeks thereafter.

Study Sites

For a full list of open sites, see the clinicaltrials.gov listing.

• California
  • San Francisco, CA
    • University of California, San Francisco
    • Contact: Michelle Melisko, MD by email   
    • Contact: Ivy Wong by email or by phone: 415-353-7873
• Illinois
  • Chicago, IL
    • University of Chicago      
    • Contact: Jerrica Hill by email
• ​​Maryland
  • Baltimore, MD
    • Johns Hopkins University  
    • Contact: Ashley Carpenter by email          
• Massachusetts
  • Boston, MA
    • Beth Israel Deaconess Medical Center
    • Contact: Nadine Tung, MD by email or by phone at: 617-667-1962
  • Boston, MA
    • Dana-Farber Cancer Institute
    • Contact: Judy Garber, MD, MPH by email
• New York
  • New York, NY
    • Memorial Sloan Kettering Cancer Center 
    • Contact: Angemaël Syldor by email     
• North Carolina
  • Durham, NC
    • Duke University
    • Contact: Michelle Parks by email 
• Pennsylvania
  • Philadelphia, PA
    • University of Pennsylvania
    • Contact: Catherine Rudloff by email    
  • Pittsburgh, PA
    • University of Pittsburgh     
    • Contact: Rometa Pollard by email    

Principal Investigator

The study PI is Nadine Tung, MD: 617-667-1962 or by email. 

Men and women with Stage IV breast cancer who do not have an inherited BRCA1 or BRCA2 mutation and:

• have a documented inherited, germline mutation in PALB2 or have a acquired (somatic) mutation in a DNA repair gene BRCA1 or BRCA2 found through biomarker testing.
• participants must have at least one site of measurable disease.
• participants may have progressed on no more than 2 prior chemotherapy lines in the metastatic setting.
• history of prior anthracycline and/or taxane based chemotherapy is preferred.
• must be willing to undergo a research biopsy before starting treatment.

Men or Women will be excluded if:

• they have an inherited mutation in BRCA1 or BRCA2 mutation.
• they have had treatment with a PARP inhibitor in the past.
• they are unable or unwilling to swallow oral medication.
• they have had another malignancy within the last 5 years other than non-melanoma skin cancer, in situ cancer of the cervix, ductal carcinoma in situ (DCIS) or stage 1 endometrial carcinoma.
• they have unstable central nervous system or brain metastasis. Stable brain metastasis is allowed.