Metastatic Breast Cancer
Conditions
Keywords
Metastatic, Locally advanced, Estradiol therapy, Estrogen therapy
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
Interventions
DRUGEstradiol
Estradiol is a therapeutic option for the treatment of advanced ER+ breast cancer
Sponsors
Dartmouth-Hitchcock Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy 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%.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Contacts
CONTACTResearch Nurse
PRINCIPAL_INVESTIGATORMuhammad Azfal, MD
Dartmouth-Hitchcock Medical Center
Outcome results
None listed