Clinical trial NCT05716516: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Metastatic Breast Cancer
Keywords: Metastatic
Locally advanced
Estradiol therapy
Estrogen therapy
Lead sponsor: Dartmouth-Hitchcock Medical Center
Sponsor class: OTHER
First posted: 2023-02-08
Enrollment: 36
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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%.

Primary outcomes:
measure: Clinical Benefit Rate
timeFrame: 12 months
Secondary outcomes:
measure: Objective response rate
timeFrame: 8 weeks
measure: Progression-free survival
timeFrame: 12 months
measure: Tumor Metabolic response
timeFrame: 12 months
measure: Adverse event profiles
timeFrame: 12 months
Other outcomes:
Locations:
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
Study officials:
affiliation: Dartmouth-Hitchcock Medical Center
name: Mary Chamberlin, MD
role: PRINCIPAL_INVESTIGATOR
References: