Estradiol Plus Olaparib for Breast Cancer (PHOEBE)

Sponsor

Gary Schwartz (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05900895

Collaborator

Dartmouth-Hitchcock Medical Center (Other)

Enrollment

Arm

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Breast Cancer	Drug: Olaparib Drug: 17b-estradiol	Phase 1

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

6 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Intervention Model Description:

Single-arm, 3+3 design with a dose-expansion cohort.Single-arm, 3+3 design with a dose-expansion cohort.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Sep 1, 2023

Anticipated Primary Completion Date :

Sep 1, 2027

Anticipated Study Completion Date :

Sep 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment Arm 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 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. Other Names: Lynparza Drug: 17b-estradiol 17b-estradiol will be taken orally three times per day. Other Names: Estrace

Arm

Intervention/Treatment

Experimental: Treatment Arm

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

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.

Other Names:

Lynparza

Drug: 17b-estradiol

17b-estradiol will be taken orally three times per day.

Other Names:

Estrace

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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).