Comprehensive Genomic Profiling of Colorectal Cancer Patients With Isolated Liver Metastases to Understand Response & Resistance to Cancer Therapy (COMPARISON)

This is a prospective study investigating the disease course of patients with colorectal cancer that have had their cancer spread to their liver. The aim of this study is find potential biomarkers for disease recurrence and therapeutic targets for prognostic information.

Study Overview

• Status: Active, not recruiting
• Conditions: Colorectal Cancer; Colorectal Cancer Metastatic; Hepatic Metastases

Detailed Description

Colorectal cancer (CRC), the 2nd leading cause of cancer mortality, often has a pattern of targeting the liver during initial metastases. The Comprehensive Genomic Profiling of Colorectal Cancer Patients with Isolated Liver Metastases to Understand Response and Resistance to Cancer Therapy (COMPARISON) study aims to assess the disease course of CRC by collecting primary tumor and metastatic liver specimens following pre-operative chemotherapy. If relapse occurs following surgical resection of the liver, biopsies will also be done for molecular analysis. As a result, these samples can be analyzed for chemotherapy resistance mechanisms and therapeutic targets to determine potential clinical outcomes for this particular subset of CRC patients.

• Study Type: Observational
• Enrollment (Actual): 17

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • Vancouver Regional Cancer Centre
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

metastatic colorectal cancer, isolated liver metastases, at least 3 rounds of chemotherapy (FOLFOX or FOLFIRI +/- Bevacizumab) prior to planned liver resection

Description

Eligibility Criteria:

1. Patients must have histologically confirmed CRC with isolated liver metastasis
2. Patients must be planned for a hepatic metastasectomy
3. Patients must have received at least 3 cycles of chemotherapy (FOLFOX or FOLFIRI with or without Bevacizumab) prior to the planned hepatic metastasectomy
4. Primary tumor must be considered resectable with a plan for this to either occur concurrently with the liver resection or subsequent to this.
5. If primary has already been resected before liver resection, archival tissue must be available for genomic analysis
6. Patients must be 18yrs of age or older
7. Ability to understand and willing to sign a written informed consent document

Exclusion Criteria:

1. Patients with un-resectable or borderline resectable isolated liver metastases as judged by the multidisciplinary hepatobiliary tumor board at PM or BCCA after a course of pre-operative chemotherapy will be excluded
2. Patients with evidence of possible metastatic disease at any sites outside the liver are not eligible
3. Patients with any major co-morbidity or co-morbidities that will render liver resection very high risk in investigator's opinion
4. Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures.
5. Patients with a previous history of another primary cancer treated within 5 years of study entry are not eligible except those with basal cell or squamous cell carcinoma of the skin and intraepithelial neoplasia.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Metastatic Colorectal Cancer with Isolated Liver Metastasis; Patients with advanced colorectal cancer with isolated liver metastasis. Primary cancer must be resectable (if no archival exists) and patient must be planned for liver resection with at least 3 cycles of chemotherapy prior to liver surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Utilization rates of characterized genomic and epigenetic features associated with chemotherapy resistance and tumor recurrence in clinical environments	5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Identification of epigenetic profiles of recurring tumor clones through serial DNA characterization on the NGS platform	5 years
Identification of epigenetic profiles of recurring tumor clones through serial RNA characterization on the NGS platform	5 years
Identification of DNA methylation profiles of recurring tumor clones through serial methylome analysis via MethylSeq	5 years
Non-invasive detection of cfDNA methylation profiles by performing ultra-deep targeted NGS on blood samples	5 years
Non-invasive detection of cfDNA methylation profiles by performing cfMeDIP-seq on blood samples	5 years

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Collaborators: British Columbia Cancer Agency; Terry Fox Research Institute
• Investigators: Principal Investigator: Kyaw Aung, MD, Princess Margaret Cancer Centre; Principal Investigator: Daniel Renouf, MD, British Columbia Cancer Agency; Principal Investigator: Lillian Siu, MD, Princess Margaret Cancer Centre

Study record dates

Study Major Dates

• Study Start (Actual): August 29, 2017
• Primary Completion (Anticipated): June 29, 2024
• Study Completion (Anticipated): June 29, 2024

Study Registration Dates

• First Submitted: November 9, 2017
• First Submitted That Met QC Criteria: November 30, 2017
• First Posted (Actual): December 6, 2017

Study Record Updates

• Last Update Posted (Actual): May 15, 2023
• Last Update Submitted That Met QC Criteria: May 12, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Sequencing; Metastasis; Liver resection; Molecular profiling; Epigenetic analysis; Genomic analysis
• 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; Neoplastic Processes; Colorectal Neoplasms; Neoplasm Metastasis
• Other Study ID Numbers: COMPARISON-001

Drug and device information, study documents

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