Overview
Determine the safety and recommended Phase II dose of olaparib in combination with 17b-estradiol in post-menopausal patients with advanced ER+/HER2- breast cancer.
Description
Patients with endocrine-resistant ER+/HER2- breast cancer are eligible. Patients will be treated with the combination of 17b-estradiol and olaparib for 2 cycles, and then treated with single-agent 17b-estradiol until disease progression. Clinical benefit, progression-free survival, objective response, tumor metabolic response, and toxicity will be determined.
Eligibility
Inclusion Criteria:
- Post-menopausal women with ER+/HER2- breast cancer.
- Metastatic or locoregional recurrence not amenable to treatment with curative intent.
- Received ≥1 prior line of endocrine-based therapy in the advanced/metastatic setting.
Exclusion Criteria:
- During study treatment, no concurrent anti-cancer therapies are allowed with the
following exceptions:
- Anti-resorptive bone therapies (e.g., bisphosphonates, denosumab) permitted.
- Any investigational cancer therapy or systemic chemotherapy in the last 3 weeks.
- Any radiation therapy in the last 2 weeks.
- Known CNS disease, unless clinically stable for ≥ 3 months.
- Concomitant use of known strong or moderate CYP3A inhibitors.
- Persistent toxicities (≥CTCAE grade 2) caused by previous cancer therapy.
- History of any of the following:
- Deep venous thrombosis
- Pulmonary embolism
- Stroke
- Acute myocardial infarction
- Congestive heart failure
- Previous malignancy not treated with curative intent, or with an estimated recurrence risk ≥30%
- Severe renal impairment (creatinine clearance ≤ 30 mL/min).