Metastatic Breast Cancer
Conditions
Keywords
metastatic, locally advanced, estradiol therapy, olaparib
Brief summary
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.
Detailed 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.
Interventions
DRUGOlaparib
Participants will be treated with olaparib at the approved doses for the treatment of subtypes of breast cancer or at reduced dose/frequency for participants with moderate renal impairment.
DRUG17b-estradiol
17b-estradiol will be taken orally three times per day.
Sponsors
Dartmouth-Hitchcock Medical Center
Mary D Chamberlin
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single-arm, 3+3 design with a dose-expansion cohort.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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: o 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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine the Phase II dose of olaparib in combination with 17b-estradiol | 8 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical benefit rate | 6 months | The proportion of evaluable patients experiencing clinical benefit (stable disease at 24 weeks, complete or partial response per RECIST) will be measured. |
| Objective response rate | 6 months | The proportion of evaluable patients experiencing objective response (complete or partial response per RECIST) will be measured. |
| Progression-free survival | 12 months | Progression-free survival will be measured by measuring the length of time between the start of study treatment until the time of cancer progression or death from any cause. |
| Plasma Olaparib concentration | 6 hours | The concentration of Olaparib in plasma will be measured over 6 hours. |
| Plasma 17b-Estradiol/Estrone concentration | 6 hours | The concentration of 17b-Estradiol/Estrone in plasma will be measured over 6 hours. |
Countries
United States
Contacts
Primary ContactResearch Nurse
Outcome results
None listed