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

Phase 2

Recruiting

• Conditions: Metastatic Breast Cancer
• Interventions: Drug: Estradiol

• Registration Number: NCT05716516
• Lead Sponsor: Dartmouth-Hitchcock Medical Center

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

Study Timeline

• Study First Submitted: 2023-01-28
• Study First Submitted QC: 2023-01-28
• Study First Posted: 2023-02-08
• Study Start: 2023-05-04
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-16
• Last Update Posted: 2024-07-17
• Primary Completion: 2026-05
• Study Completion: 2027-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 36

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Clinical Benefit Rate	12 months	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.

Secondary Outcome Measures

Name	Time	Method
Objective response rate	8 weeks	The objective response rate (complete + partial responses) to the first 8 weeks of treatment with 17b-estradiol will be ascertained and compared between subjects harboring amplified/mutant ESR1 and wild-type ESR1.
Progression-free survival	12 months	Progression-free survival with 17b-estradiol treatment will be ascertained and compared between subjects harboring amplified/mutant ESR1 and wild-type ESR1.
Tumor Metabolic response	12 months	Tumor metabolic response will be defined as the best response at any time point per PERCIST. The metabolic response rate (complete + partial metabolic response) will be ascertained and compared between subjects treated with 17b-estradiol harboring amplified/mutant ESR1 and wild-type ESR1.
Adverse event profiles	12 months	The number of participants with treatment-related adverse events as assessed by CTCAE v5.0 will be collected

Trial Locations

Locations (1)

Dartmouth-Hitchcock Medical Center; 🇺🇸 Lebanon, New Hampshire, United States