Detection of MSI in Circulating Tumor DNA of Colorectal Carcinoma Patients

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

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.

Study Overview

• Status: Terminated
• Conditions: Microsatellite Instability; Colorectal Cancer Stage IV
• Intervention / Treatment: Procedure: Specimen Collection; Procedure: Serial Liquid Biopsy

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 6

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • USC / Norris Comprehensive Cancer Center
    • Newport Beach, California, United States, 92663
      • USC Norris Oncology/Hematology-Newport Beach

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients newly diagnosed with stage IV colorectal cancer and with defined microsatellite instability status before initiation of systemic immunotherapy will be recruited.

Description

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).

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Ancillary-correlative (Specimen collection); 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; Undergo collection of blood samples; Procedure: Serial Liquid Biopsy; Undergo serial liquid biopsy

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Southern California
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Heinz Josef Lenz, MD, University of Southern California

Study record dates

Study Major Dates

• Study Start (Actual): September 5, 2018
• Primary Completion (Actual): September 18, 2023
• Study Completion (Actual): September 18, 2023

Study Registration Dates

• First Submitted: July 11, 2018
• First Submitted That Met QC Criteria: July 11, 2018
• First Posted (Actual): July 20, 2018

Study Record Updates

• Last Update Posted (Actual): August 29, 2024
• Last Update Submitted That Met QC Criteria: August 27, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Genomic Instability; Colorectal Neoplasms; Microsatellite Instability
• Other Study ID Numbers: 3C-18-2 (Other Identifier: USC / Norris Comprehensive Cancer Center); P30CA014089 (U.S. NIH Grant/Contract); NCI-2018-01169 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No