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

Primary Purpose

Metastatic Breast Cancer

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Olaparib
17b-estradiol
Sponsored by
Gary Schwartz
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Breast Cancer focused on measuring metastatic, locally advanced, estradiol therapy, olaparib

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept 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).

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Treatment Arm

    Arm Description

    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.

    Outcomes

    Primary Outcome Measures

    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.

    Secondary Outcome Measures

    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.
    Objective response rate
    The proportion of evaluable patients experiencing objective response (complete or partial response per RECIST) will be measured.
    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.
    Plasma Olaparib concentration
    The concentration of Olaparib in plasma will be measured over 6 hours.
    Plasma 17b-Estradiol/Estrone concentration
    The concentration of 17b-Estradiol/Estrone in plasma will be measured over 6 hours.

    Full Information

    First Posted
    May 24, 2023
    Last Updated
    June 2, 2023
    Sponsor
    Gary Schwartz
    Collaborators
    Dartmouth-Hitchcock Medical Center
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05900895
    Brief Title
    Estradiol Plus Olaparib for Breast Cancer (PHOEBE)
    Acronym
    PHOEBE
    Official Title
    Phase 1b Study of Olaparib and Estradiol in Advanced ER+ Breast Cancer (PHOEBE)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    June 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    September 2023 (Anticipated)
    Primary Completion Date
    September 2027 (Anticipated)
    Study Completion Date
    September 2028 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor-Investigator
    Name of the Sponsor
    Gary Schwartz
    Collaborators
    Dartmouth-Hitchcock Medical Center

    4. Oversight

    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

    5. 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.
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Metastatic Breast Cancer
    Keywords
    metastatic, locally advanced, estradiol therapy, olaparib

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Sequential Assignment
    Model Description
    Single-arm, 3+3 design with a dose-expansion cohort.
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    6 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Treatment Arm
    Arm Type
    Experimental
    Arm Description
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    Olaparib
    Other Intervention Name(s)
    Lynparza
    Intervention Description
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    17b-estradiol
    Other Intervention Name(s)
    Estrace
    Intervention Description
    17b-estradiol will be taken orally three times per day.
    Primary Outcome Measure Information:
    Title
    Determine the Phase II dose of olaparib in combination with 17b-estradiol
    Description
    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.
    Time Frame
    8 weeks
    Secondary Outcome Measure Information:
    Title
    Clinical benefit rate
    Description
    The proportion of evaluable patients experiencing clinical benefit (stable disease at 24 weeks, complete or partial response per RECIST) will be measured.
    Time Frame
    6 months
    Title
    Objective response rate
    Description
    The proportion of evaluable patients experiencing objective response (complete or partial response per RECIST) will be measured.
    Time Frame
    6 months
    Title
    Progression-free survival
    Description
    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.
    Time Frame
    12 months
    Title
    Plasma Olaparib concentration
    Description
    The concentration of Olaparib in plasma will be measured over 6 hours.
    Time Frame
    6 hours
    Title
    Plasma 17b-Estradiol/Estrone concentration
    Description
    The concentration of 17b-Estradiol/Estrone in plasma will be measured over 6 hours.
    Time Frame
    6 hours

    10. Eligibility

    Sex
    Female
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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).
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Research Nurse
    Phone
    1-800-639-6918
    Email
    Cancer.Research.Nurse@dartmouth.edu
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Gary Schwartz, MD
    Organizational Affiliation
    Dartmouth-Hitchcock Medical Center
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

    Estradiol Plus Olaparib for Breast Cancer (PHOEBE)

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