Clinical trial NCT03364621: Comprehensive Genomic Profiling of Colorectal Cancer Patients With Isolated Liver Metastases to Understand Response & Resistance to Cancer Therapy
Official title: Comprehensive Genomic Profiling of Colorectal Cancer Patients With Isolated Liver Metastases to Understand Response & Resistance to Cancer Therapy
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Colorectal Cancer
Colorectal Cancer Metastatic
Hepatic Metastases
Keywords: Liver resection
Metastasis
Molecular profiling
Epigenetic analysis
Genomic analysis
Sequencing
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: Terry Fox Research Institute
name: British Columbia Cancer Agency
First posted: 2017-12-06
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Utilization rates of characterized genomic and epigenetic features associated with chemotherapy resistance and tumor recurrence in clinical environments
timeFrame: 5 years
Secondary outcomes:
measure: Identification of epigenetic profiles of recurring tumor clones through serial DNA characterization on the NGS platform
timeFrame: 5 years
measure: Identification of epigenetic profiles of recurring tumor clones through serial RNA characterization on the NGS platform
timeFrame: 5 years
measure: Identification of DNA methylation profiles of recurring tumor clones through serial methylome analysis via MethylSeq
timeFrame: 5 years
measure: Non-invasive detection of cfDNA methylation profiles by performing ultra-deep targeted NGS on blood samples
timeFrame: 5 years
measure: Non-invasive detection of cfDNA methylation profiles by performing cfMeDIP-seq on blood samples
timeFrame: 5 years
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: Vancouver Regional Cancer Centre
state: British Columbia
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
Study officials:
affiliation: Princess Margaret Cancer Centre
name: Lillian Siu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Princess Margaret Cancer Centre
name: Kyaw Aung, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: British Columbia Cancer Agency
name: Daniel Renouf, MD
role: PRINCIPAL_INVESTIGATOR
References: