Estradiol Plus Olaparib for Breast Cancer (PHOEBE)

NCT05900895 | Recruiting Phase 1 FDA Drug

• 1 other identifier: STUDY02002007
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Breast Cancer

Keywords

metastatic; locally advanced; estradiol therapy; olaparib

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Clinical benefit rate

  6 months

• Objective response rate

  6 months

• Progression-free survival

  12 months

• Plasma Olaparib concentration

  6 hours

• Plasma 17b-Estradiol/Estrone concentration

  6 hours

Study Arms (1)

Treatment Arm

EXPERIMENTAL

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; Drug: 17b-estradiol

Interventions

Olaparib DRUG

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.

Also known as: Lynparza

Treatment Arm

17b-estradiol DRUG

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

Also known as: Estrace

Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Mary D Chamberlin: lead
• Dartmouth-Hitchcock Medical Center: collaborator

Study Sites (1)

Dartmouth Cancer Center

Lebanon, New Hampshire, 03756, United States

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

olaparib; Estradiol

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Mary Chamberlin, MD

  Dartmouth-Hitchcock Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Research Nurse

CONTACT

1-800-639-6918; Cancer.Research.Nurse@dartmouth.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

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

Study Record Dates

• First Submitted: May 24, 2023
• First Posted: June 13, 2023
• Study Start: July 15, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: November 20, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)