Plasma Circulating Tumor DNA Analyses in ER+ Metastatic Breast Cancer

Study Overview
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Brief Summary
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The purpose of this study is to evaluate whether increased mutant ESR1 allele fraction in plasma ctDNA 3-6 weeks after initiating salvage endocrine therapy is predictive of progression free survival in patients with ER+ metastatic breast cancer.

Detailed Description
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The primary objective of this 110 patient correlative biomarker study is to evaluate whether changes in mutant ESR1 allele fraction in plasma circulating tumor DNA (ctDNA) are predictive of progression-free survival in metastatic ER+ breast cancer patients who are receiving 2nd, 3rd, or 4th line systemic endocrine therapy. A secondary goal of this study is to explore the prevalence and kinetics of hotspot and non-hotspot ctDNA ESR1 mutations in this patient population, prior to initiating a new line of endocrine therapy as well as upon clinical progression, to identify potential mechanisms of resistance. Although initially to be opened at UNC Chapel Hill, our goal is to expand enrollment to include Rex Cancer Center in Raleigh, North Carolina, and collaborating institutions through the Translational Breast Cancer Research Consortium.

Official Title
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LCCC 1642: Plasma Circulating Tumor DNA (ctDNA) Analyses in ER+ Metastatic Breast Cancer

Conditions
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Metastatic Breast Cancer

Intervention / Treatment
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* Other: Observational


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years of age Female gender Biopsy proven diagnosis of breast cancer Stage IV disease diagnosed either by radiographic studies or biopsy ER+ by immunohistochemistry on primary and/or metastatic tissue biopsy (>10%) HER2 non-amplified (1+ or below by immunohistochemistry, and/or Her2 FISH <2 HER2-to-CEP17 ratio) Progressed on at least one prior line of endocrine therapy for metastatic disease Three or fewer prior endocrine-containing therapies for recurrent/metastatic disease Two or fewer prior lines of cytotoxic chemotherapy for recurrent/metastatic disease Plans to initiate 2nd, 3rd, or 4th line endocrine therapy for metastatic disease Recent re-staging scans within 4 weeks of study enrollment, with radiographically identifiable disease No concurrent or prior diagnosis of malignancy other than breast cancer for the past 5 years. Patients with a history of in situ cancer or basal or localized squamous cell skin cancer remain eligible Intends to pursue treatment as well as clinical and radiographic follow-up at UNC Health Care Signed an institutional review board (IRB)-approved informed consent document for this protocol and HIPAA consent form Exclusion Criteria: < 18 years of age Tissue biopsies that support the presence of both ER+ and ER- metastatic breast cancer in the same patient Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent Pregnant or lactating women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: Observational|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival Prediction | To evaluate whether increased mutant ESR1 allele fraction in plasma ctDNA 3-6 weeks after initiating salvage endocrine therapy is predictive of progression free survival in patients with ER+ metastatic breast cancer. | Through study completion, an average of 3-6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DNA Analysis of Hotspot Mutation Prevalence | To evaluate the overall spectrum and prevalence of hotspot and non-hotspot ESR1 mutations in plasma ctDNA prior to initiating 2nd, 3rd, or 4th endocrine therapy and after clinical disease progression. | Through study completion, an average of 3-6 weeks | 
| DNA Analysis of Mutation and Radiographic Response Correlation | Exploratory analysis of whether changes in mutant ESR1 allele fraction in plasma ctDNA at the time of re-staging scans correlates with radiographic response. | Through study completion, an average of 3-6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DNA, Circulating tumor cells