HOPE: Olaparib, Palbociclib and Fulvestrant in Patients With BRCA Mutation-associated, HR+, HER2-metastatic Breast Cancer

Inclusion Criteria

• •Females/males ≥ age 18
• •Germline or somatic deleterious or suspected deleterious mutation in BRCA1 or BRCA2
• •Metastatic or locally advanced unresectable breast cancer that is ER and/or PR positive (\>1%) and HER2 nonamplified
• •Prior treatment with 0-2 prior lines of chemotherapy for metastatic breast cancer
• •Regarding prior platinum-based chemotherapy:
• •2. Patients who received platinum for advanced breast cancer are eligible to enter the study provided there was no evidence of disease progression during the platinum chemotherapy.
• •3. Patients who received prior platinum-based as a potentially curative treatment for a prior non-breast cancer (e.g., ovarian cancer) with no evidence of disease for 5 years or greater prior to study entry are permitted.
• •Deemed a candidate for endocrine therapy (any prior endocrine therapy is permitted; no prior endocrine therapy is also permitted)
• •Adequate organ and bone marrow function
• •ECOG performance status 0-1
• •At least one measurable disease or disease that can be assessed by CT or MRI
• •Life expectancy ≥ 16 weeks
• •Postmenopausal as defined below. Women who are on pharmacologic ovarian suppression must have two negative urine or serum pregnancy tests: one during screening (within 28 days prior to study treatment) and one within 7 days prior to commencing treatment.
• •Postmenopausal is defined as one of the below:
• •Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments
• •Follicle stimulating hormone (FSH) levels in the post-menopausal range for women under 50
• •radiation-induced oophorectomy with last menses \>1 year ago
• •chemotherapy-induced menopause with \>1 year interval since last menses
• •bilateral oophorectomy or hysterectomy
• •on luteinizing hormone-releasing hormone (LHRH) agonists according to current clinical practice standards as pharmacologic ovarian suppression
• •Female patients of childbearing potential (not post-menopausal as defined above) must agree to the use of two highly effective forms of contraception in combination throughout the period of taking study treatment and for 1 month after last dose of study drug(s) to prevent pregnancy.
• •Male patients and their sexual partners of childbearing potential must agree to the use of two highly effective forms of contraception in combination throughout the period of taking study treatment and for 3 months after last dose of study drug(s) to prevent pregnancy in a partner.
• •Willing to comply with study requirements and procedures including use of appropriate contraception, willingness to discontinue herbal preparations / medications, and study biopsy if archival tissue is not available