RecruitingInterventionalPhase 2

Phase II Study of Estradiol Therapy to Target ER-Mutant and ER-Wild-Type ER+ Metastatic or Advanced Breast Cancer

NCT ID: NCT05716516Sponsor: Dartmouth-Hitchcock Medical CenterLast updated: 2026-05-05

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

Arms & interventions

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

Outcome measures

Primary

Clinical Benefit Rate
The clinical benefit rate (complete responses + partial responses + stable disease at 24 weeks) will be ascertained and compared between subjects treated with 17b-estradiol harboring amplified/mutant ESR1 and wild-type ESR1.
Time frame: 12 months

Secondary

Objective response rate
Time frame: 8 weeks
Progression-free survival
Time frame: 12 months
Tumor Metabolic response
Time frame: 12 months
Adverse event profiles
Time frame: 12 months

Eligibility criteria

Sex: FemaleAge: 18 Years and olderHealthy volunteers: No

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%.

Study locations (1)

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756

Recruiting