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

Official title

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

Overview

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

Interventions

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

Primary outcome measures

• Clinical Benefit Rate [Time frame: 12 months]

Secondary outcome measures (4)

• 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

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%.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Dartmouth-Hitchcock Medical Center — Lebanon

Identifiers

NCT: NCT05716516 · STUDY02001740 · NCI-2023-05453

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗