Estradiol Plus Olaparib for Breast Cancer (PHOEBE)

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase 1b Study of Olaparib and Estradiol in Advanced ER+ Breast Cancer (PHOEBE)

Conditions
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Metastatic Breast Cancer

Intervention / Treatment
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* Drug: Olaparib
* Drug: 17b-estradiol


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Interventional Model Description: Single-arm, 3+3 design with a dose-expansion cohort.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm<br>Participants receive 2 cycles of olaparib in combination with 17b-estradiol and then continue to be treated with single-agent 17b-estradiol until disease progression. | Drug: Olaparib<br>* 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.<br>* Other names: Lynparza;Drug: 17b-estradiol<br>* 17b-estradiol will be taken orally three times per day.<br>* Other names: Estrace;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the Phase II dose of olaparib in combination with 17b-estradiol | 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. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical benefit rate | The proportion of evaluable patients experiencing clinical benefit (stable disease at 24 weeks, complete or partial response per RECIST) will be measured. | 6 months | 
| Objective response rate | The proportion of evaluable patients experiencing objective response (complete or partial response per RECIST) will be measured. | 6 months | 
| Progression-free survival | 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. | 12 months | 
| Plasma Olaparib concentration | The concentration of Olaparib in plasma will be measured over 6 hours. | 6 hours | 
| Plasma 17b-Estradiol/Estrone concentration | The concentration of 17b-Estradiol/Estrone in plasma will be measured over 6 hours. | 6 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metastatic, locally advanced, estradiol therapy, olaparib