This phase II trial tests how well estradiol therapy works in treating estrogen receptor (ER) positive breast cancer with known estrogen receptor 1 (ESR1) gene mutation and wild-type status that has spread from where it first started (the breast) to other places in the body (metastatic) or that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Patients with ER positive breast cancer are typically treated with anti-estrogen therapies that blocks ER signaling; however, patients can develop a resistance to anti-estrogen drugs, where the cancer remains despite treatment. Upon the development of anti-estrogen-resistant breast cancer, patients can be treated with estradiol. Estradiol is an estrogen hormone that naturally occurs in humans and is a type of hormone replacement therapy that is used to relieve symptoms of low estrogen. Although not clearly understood, this form of high dose estrogen replacement therapy has been shown to cause the death of tumor cells in breast cancer cell lines in patients with metastatic or advanced disease. The ESR1 gene which encodes the ER can be mutated or changed, or it can be amplified, in which there are multiple copies of the ESR1 gene. If the ESR1 gene is unchanged it is referred to as wild-type. ESR1-mutant/amplified and ESR1-wild-type are two states of the ESR1 gene found in ER positive breast cancer, and are being compared in this study. These ESR1 alterations are examples of biomarkers. Biomarkers are substances inside the body that can signal normal or abnormal processes within the body. They may also be used to learn about how a type of cancer may react to treatment. By evaluating the response to estradiol treatment based on ESR1 status, researchers may be able to gain a better understanding of how biomarkers, such as ESR1, can be used to direct treatment decisions in future patients with breast cancer.
Additional locations may be listed on ClinicalTrials.gov for NCT05716516.
Locations matching your search criteria
United States
New Hampshire
Lebanon
Dartmouth Hitchcock Medical Center/Dartmouth Cancer CenterStatus: Active
Contact: Mary Dickinson Chamberlin
Phone: 603-653-6181
PRIMARY OBJECTIVE:
I. Determine whether subjects harboring ESR1-mutant/amplified breast cancer have a higher rate of clinical benefit from therapeutic estradiol (17 beta-[17b]-estradiol) therapy than subjects with ESR1-wild-type breast cancer.
SECONDARY OBJECTIVES:
I. Determine whether subjects harboring ESR1-mutant/amplified breast cancer have a higher objective response rate from 17b-estradiol therapy than subjects with ESR1-wild-type breast cancer.
II. Determine whether subjects harboring ESR1-mutant/amplified breast cancer have longer progression-free survival on 17b-estradiol therapy than subjects with ESR1-wild-type breast cancer.
III. Determine whether subjects harboring ESR1-mutant/amplified breast cancer have a higher tumor metabolic response rate from 17b-estradiol therapy than subjects with ESR1-wild-type breast cancer.
IV. Determine the adverse event profile of 17b-estradiol in this patient population.
EXPLORATORY OBJECTIVES:
I. Identify genetic lesions in tumor tissue and plasma predictive of clinical benefit, objective response, tumor metabolic response, and progression-free survival on 17b-estradiol.
II. Determine the rate of clinical benefit and interval of progression-free survival from physician’s choice therapy in patients previously treated with 17b-estradiol as the prior line of therapy, and determine whether response to 17b-estradiol predicts response to next-line therapy.
III. Determine whether a higher tumor baseline signature of estrogen receptor (ER) transcriptional activity is predictive of sensitivity to 17b-estradiol therapy.
IV. Identify molecular changes that occur in response to 17b-estradiol therapy in tumors.
OUTLINE:
Patients receive 17b-estradiol orally (PO) three times daily (TID) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patient also undergo positron emission tomography (PET)/computed tomography (CT) or CT with bone scan throughout the trial. Patients undergo blood sample collection during screening, on study, and at disease progression and may undergo tumor biopsy on study.
After completion of study treatment, patients are followed up to 30 days or may optionally be treated with physician’s choice and monitored for response during the observational phase of the study until disease progression.
Lead OrganizationDartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Principal InvestigatorMary Dickinson Chamberlin