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

Metastatic Breast Cancer Clinical Trial

— ESTHER  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05716516
• Other study ID #: 22SCH740
• Status: Recruiting
• Phase: Phase 2
• Start date: May 4, 2023
• Est. completion date: May 2027

Study information

• Verified date: November 2023
• Source: Dartmouth-Hitchcock Medical Center
• Contact: Research Nurse
• Phone: 1-800-639-6918
• Email: Cancer.Research.Nurse[@]dartmouth.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: May 2027
• Est. primary completion date: May 2026
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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%.

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

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

Locations

Country	Name	City	State
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire

Sponsors (1)

Lead Sponsor	Collaborator
Dartmouth-Hitchcock Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	12 months
Secondary	Objective response rate	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.	8 weeks
Secondary	Progression-free survival	Progression-free survival with 17b-estradiol treatment will be ascertained and compared between subjects harboring amplified/mutant ESR1 and wild-type ESR1.	12 months
Secondary	Tumor Metabolic response	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.	12 months
Secondary	Adverse event profiles	The number of participants with treatment-related adverse events as assessed by CTCAE v5.0 will be collected	12 months