Plasma Circulating Tumor DNA Analyses in ER+ Metastatic Breast Cancer

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Other: Observational

Detailed Description

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.

• Study Type: Observational

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

Females with ER+ metastatic breast cancer receiving 2nd, 3rd, or 4th line systemic endocrine therapy

Description

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

Study Plan

How is the study designed?

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: UNC Lineberger Comprehensive Cancer Center
• Investigators: Principal Investigator: Gaorav P Gupta, MD, PhD, University of North Carolina, Chapel Hill

Publications and helpful links

Helpful Links

• UNC Lineberger Comprehensive Cancer Center Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2017
• Primary Completion (Actual): July 9, 2020
• Study Completion (Actual): July 9, 2020

Study Registration Dates

• First Submitted: May 15, 2017
• First Submitted That Met QC Criteria: May 18, 2017
• First Posted (Actual): May 22, 2017

Study Record Updates

• Last Update Posted (Actual): May 21, 2021
• Last Update Submitted That Met QC Criteria: May 18, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: DNA; Circulating tumor cells
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: LCCC 1642; 16-2952 (Other Identifier: UNC IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No