STUDY02001740;22SCH740: Estradiol For ER+ Advanced Breast Cancer (ESTHER)

NCT ID: NCT05716516

Last Updated: 2026-01-14

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-05-04
• Study Completion Date: 2027-05-31

Brief Summary

Determine whether subjects harboring ESR1-mutant/amplified breast cancer have a higher rate of clinical benefit from 17b-estradiol therapy than subjects with ESR1-wild-type breast cancer

Detailed Description

Patients with endocrine-resistant breast cancer are eligible. Treatment Phase: Patients will be treated with 17b-estradiol until disease progression. At this point, the patient will end protocol therapy. Clinical benefit, progression-free survival, objective response, tumor metabolic response, and toxicity will be determined. Observational Phase (optional): After disease progression on 17b-estradiol, patients will be treated at their oncologist's discretion. Clinical benefit, progression-free survival, and objective response will be measured during this line of treatment of physician's choice until another instance of disease progression. In consented subjects who undergo a clinically indicated tumor biopsy of recurrent or metastatic disease prior to the start of 17b-estradiol treatment, when feasible, acquisition of additional tumor tissue is requested for research purposes. Optional: patients will be asked to provide tumor tissue via a research biopsy on Day 3-4 of 17b-estradiol treatment. Archived tumor tissue and clinical-grade tumor and plasma DNA/RNA sequencing results will be used for research purposes. Blood samples will be obtained at baseline, on Day 3-4 of 17b-estradiol therapy (optional), and upon disease progression on 17b-estradiol. Plasma and buffy coat will be extracted and frozen. Tumor tissue and plasma specimens will be analyzed to identify molecular biomarkers predictive of sensitivity/resistance to 17b-estradiol therapy

Conditions

Metastatic Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment Arm

Treatment Phase: Patients will be treated with 17b-estradiol until disease progression. At this point, the patient will end protocol therapy

Group Type: OTHER

Estradiol

Intervention Type: DRUG

Estradiol is a therapeutic option for the treatment of advanced ER+ breast cancer

Interventions

Estradiol

Estradiol is a therapeutic option for the treatment of advanced ER+ breast cancer

Intervention Type: DRUG

Other Intervention Names

Estrace

Eligibility Criteria

Inclusion Criteria

• Post-menopausal women with ER+ breast cancer.
• Metastatic or locoregional recurrence not amenable to treatment with curative
• intent.
• Received ≥1 prior line of endocrine-based therapy (e.g., including tamoxifen, aromatase inhibitors, fulvestrant, or combinations) in the advanced/metastatic setting

Exclusion Criteria

• During the study Treatment Phase with 17b-estradiol, no concurrent anti-cancer therapies are allowed with the following exceptions:

• Exception: Trastuzumab is allowed for the treatment of subjects with a history of HER2+ disease, and will be used at the physician's discretion.
• Exception: Anti-resorptive bone therapies (e.g., bisphosphonates, denosumab) are permitted.
• Any investigational cancer therapy in the last 3 weeks.
• Known CNS disease, unless clinically stable for ≥ 3 months.
• 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%.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Dartmouth-Hitchcock Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Muhammad.Z.Afzal

Associate Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mary Chamberlin, MD

Role: PRINCIPAL_INVESTIGATOR

Dartmouth-Hitchcock Medical Center

Locations

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Research Nurse

Role: CONTACT

Cancer.Research.Nurse@dartmouth.edu

1-800-639-6918

Other Identifiers

NCI-2023-05453

Identifier Type: OTHER

Identifier Source: secondary_id

STUDY02001740

Identifier Type: -

Identifier Source: org_study_id