Estradiol Plus Olaparib for Breast Cancer (PHOEBE) (PHOEBE)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: Olaparib; Drug: 17b-estradiol

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 Type: Interventional
• Enrollment (Estimated): 6
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Research Nurse; Phone Number: 1-800-639-6918; Email: Cancer.Research.Nurse@dartmouth.edu

Study Locations

• United States
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Recruiting
      • Dartmouth Cancer Center
      • Principal Investigator: Mary D Chamberlin, MD
      • Contact: Mary D Chamberlin, MD; Phone Number: 603-653-6181; Email: mary.d.chamberlin@hitchcock.org
      • Contact: Ashley E Gaughan-Maher, MA; Phone Number: 603-653-0628; Email: ashley.e.gaughan-maher@hitchcock.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Mary D Chamberlin
• Collaborators: Dartmouth-Hitchcock Medical Center
• Investigators: Principal Investigator: Mary Chamberlin, MD, Dartmouth-Hitchcock Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: May 24, 2023
• First Submitted That Met QC Criteria: June 2, 2023
• First Posted (Actual): June 13, 2023

Study Record Updates

• Last Update Posted (Actual): November 20, 2025
• Last Update Submitted That Met QC Criteria: November 17, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: olaparib; metastatic; locally advanced; estradiol therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Neoplastic Processes; Skin Diseases; Breast Diseases; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Breast Neoplasms; Neoplasm Metastasis; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Estrenes; Estranes; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Estradiol; olaparib
• Other Study ID Numbers: STUDY02002007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes