Detection of MSI in Circulating Tumor DNA of Colorectal Carcinoma Patients

Study Overview
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Brief Summary
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This pilot trial studies how well serial liquid biopsies work in detecting microsatellite instability in participants with stage IV colorectal cancer. Serial liquid biopsies may help doctors learn better methods to track cancer in the bloodstream and how to use these to improve cancer treatments.

Detailed Description
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PRIMARY OBJECTIVES: I. To test the hypothesis that there is high level of concordance between the electrophoretic mobility profile of microsatellite biomarkers in circulating cell-free deoxyribonucleic acid (ccfDNA) versus in primary tumor tissues in patients with colorectal carcinomas displaying microsatellite instability. II. To test the hypothesis that changes in the electrophoretic mobility profile of microsatellite biomarkers in liquid biopsies from patients with colorectal carcinoma correlate with therapeutic responsiveness measured based on Response Evaluation Criteria in Solid Tumors (RECIST) criteria. III. To determine whether microsatellite alleles generated as a result of microsatellite instability detectable in liquid biopsy specimens from patients with colorectal carcinoma represent the entire cancer cell population or only a subset of cancer cells differentially affected by genomic instability. OUTLINE: Participants undergo collection of blood samples to evaluate microsatellite instability via serial liquid biopsies at baseline, then every 6 weeks and at progression or 9 months.

Official Title
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Detection of Microsatellite Instability (MSI) in Circulating Tumor DNA of Patients With Stage IV Colorectal Carcinoma

Conditions
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Microsatellite Instability, Colorectal Cancer Stage IV

Intervention / Treatment
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* Procedure: Specimen Collection
* Procedure: Serial Liquid Biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients newly diagnosed with stage IV colorectal cancer and with defined microsatellite instability status before initiation of systemic immunotherapy. Trackable cancer-driver mutation in the primary tumor documented before initiation of chemotherapy. Zubrod performance status of 0 or 1. Patients have measurable disease according to RECIST version (v)1.1. Ability to understand and willing to sign a written informed consent. Exclusion Criteria: Severe anemia (hemoglobin [Hb] < 8 g/dL).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Ancillary-correlative (Specimen collection)<br>Participants undergo collection of blood samples in addition to the usual amount collected when they come in for their regular cancer treatments or doctor?s appointment every 6-8 weeks until disease progression or stopping at 9 months. | Procedure: Specimen Collection<br>* Undergo collection of blood samples<br>Procedure: Serial Liquid Biopsy<br>* Undergo serial liquid biopsy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between presence of MSI present in circulating tumor DNA versus in primary tumor specimens | MSI testing distinguishes between tumors into one of 3 phenotypic categories: MSI-High (MSI-H) is reported when > 30% of biomarkers show instability; Microsatellite stable (MSS) is reported in the absence of instability. The third category, MSI-Low (MSI-L) is diagnostically equivalent to MSS, and is reported when MSI is present in < 30% of biomarkers. MSI status will be determined by polymerase chain reaction (PCR) using commercial kits provided by Promega. | Up to 1 year |