High Definition Single Cell Analysis in Colorectal Cancer

This research clinical trial studies high definition single cell analysis in blood and tissue samples from patients with colorectal cancer which has spread to the liver. High definition single cell analysis allows doctors to study the properties of cancer cells that are sometimes found in the blood of patients and to determine how the genes and proteins in them may change over time. Studying samples from patients with colorectal cancer in the laboratory may help doctors learn more about how cancer spreads, as well as how to predict the disease outcomes in patients with cancer.

Study Overview

• Status: Completed
• Conditions: Stage IV Colorectal Cancer; Metastatic Carcinoma in the Liver
• Intervention / Treatment: Other: Biomarker Analysis; Other: Cytology Specimen Collection Procedure

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the level of correlation between solid tumor touch preparations and liquid biopsies (circulating tumor cells [CTCs]) from patients with surgically resected colorectal cancer (CRC) metastases to the liver using single-cell high-content analysis, including gene copy number variation (CNV) and to establish one or more bio-signatures that represent the liquid and solid biopsy correlation for each patient and for the patient population.

SECONDARY OBJECTIVES:

I. To demonstrate the technical validity and reproducibility of the bio-signatures by comparing the two pre-resection liquid biopsy samples drawn one week prior to and on the day of surgery.

TERTIARY OBJECTIVES:

I. Compare biosignatures between pre-surgical and post-surgical blood samples. II. Compare biosignatures between resected metastatic liver tumor tissue, primary colon tumor tissue (if available), and pre-surgical blood samples.

III. Compare biosignatures between blood samples prior to resection with those obtained after resection and at the time of recurrence.

OUTLINE:

Patients undergo blood collection 1 week prior surgery, before and after surgery on the same day, and 1 week and 3 months after surgery. Patients also undergo tissue collection during the surgery. Blood and tissue samples are processed for high definition single cell analysis including whole-genome CNV profiles, protein expression, and cell morphology.

After completion of study, patients are followed up for up to 2 years.

• Study Type: Observational
• Enrollment (Actual): 24

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92037
      • Scripps Cancer Center
    • Los Angeles, California, United States, 90033
      • USC / Norris Comprehensive Cancer Center
    • Los Angeles, California, United States, 90033
      • Los Angeles County-USC Medical Center
    • Newport Beach, California, United States, 92663
      • Hoag Memorial Hospital Presbyterian
    • Newport Beach, California, United States, 92663
      • USC Norris Oncology/Hematology-Newport Beach
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

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 with metastatic CRC with single- and multi-focal hepatic lesions scheduled for resection (metastatectomy)

Description

Inclusion Criteria:

• Able to provide informed consent

• Metastatic colorectal adenocarcinoma to the liver (hepatic mCRC)

  • Synchronous or metachronous
  • Solitary or multifocal
  • Concurrent abdominal lymph node metastasis is allowable
• Hepatic mCRC deemed surgically resectable by the study team with plans to undergo surgery
• Has not received any systemic chemotherapy for at least 21 days prior to scheduled hepatic resection

Exclusion Criteria:

• Non-adenocarcinoma metastatic colorectal cancer (e.g. neuroendocrine carcinoma); mucinous component is permitted
• Metastatic CRC that involves organ(s)/tissue(s) other than abdominal lymph nodes and/or liver
• Has received any systemic chemotherapy within 21 days prior to scheduled hepatic resection

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Ancillary-Correlative (blood and tumor tissue collection); Patients undergo collection of blood collection 1 week prior surgery, before and after surgery on the same day, and 1 week and 3 months after surgery. Patients also undergo and tissue collection during the surgery. Blood and tissue samples are processed for high definition single cell analysis including, whole-genome CNV profiles, protein expression, and cell morphology.

Other: Biomarker Analysis; Correlative studies; Other: Cytology Specimen Collection Procedure; Undergo collection of blood and tissue samples; Other Names: Cytologic Sampling

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HD-SCA liquid biopsy biosignatures assessed by cell morphology, protein expression, and whole genome CNV profiles	Biosignatures will be compared between cells from tumor tissue within the same patient, cells from blood samples within the same patient, cells from tumor tissue and blood samples within the same patient, cells from tumor tissue and blood samples across different patients. Upon these comparisons, biosignatures will be established which represent liquid and solid biopsy correlations for each patient and for the patient population. Descriptive statistics will be used to determine means, correlations, and variability of biosignatures between different specimens and time points, and within and acr	Up to 2 years
HD-SCA solid tumor biosignatures assessed by cell morphology, protein expression, and whole genome CNV profiles	Biosignatures will be compared between cells from tumor tissue within the same patient, cells from blood samples within the same patient, cells from tumor tissue and blood samples within the same patient, cells from tumor tissue and blood samples across different patients. Upon these comparisons, biosignatures will be established which represent liquid and solid biopsy correlations for each patient and for the patient population. Descriptive statistics will be used to determine means, correlations, and variability of biosignatures between different specimens and time points, and within and acr	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HD-SCA biosignatures in pre-resection liquid biopsy samples assessed by cell morphology, protein expression, and whole genome CNV profiles	The technical validity and reproducibility of the biosignatures will be demonstrated by comparing two pre-resection liquid biopsy samples. This reflects a change in the timing of specimen collection from the original protocol. Descriptive statistics will be used to determine means, correlations, and variability of biosignatures between different specimens and time points, and within and across patients.	Up to day 1 of surgery

Collaborators and Investigators

• Sponsor: University of Southern California
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Peter Kuhn, University of Southern California

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2016
• Primary Completion (Actual): May 29, 2020
• Study Completion (Actual): May 29, 2020

Study Registration Dates

• First Submitted: June 19, 2016
• First Submitted That Met QC Criteria: June 19, 2016
• First Posted (Estimated): June 22, 2016

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 9, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: 3C-15-4 (Other Identifier: USC / Norris Comprehensive Cancer Center); P30CA014089 (U.S. NIH Grant/Contract); NCI-2016-00736 (Registry Identifier: CTRP (Clinical Trial Reporting Program))