Plasma 5hmC Signatures as a Marker of Colorectal / Appendiceal Peritoneal Metastasis

5-hydroxymethylation Signatures in Plasma Circulating Cell-free DNA as Markers for Tumor Burden and Recurrence in Appendiceal and Colorectal Peritoneal Metastasis

Patients with peritoneal metastasis of colorectal or high grade appendiceal origin who are candidates for cytoreductive surgery with HIPEC (hyperthermic intraperitoneal chemotherapy) will be enrolled in this study. Blood collection for measurements of plasma cell-free DNA hydroxymethylation signatures will be performed at different time points, before and after surgery, in order to determine if plasma hydroxymethylation signatures are more sensitive than conventional tumor markers in identifying clinically detectable recurrence at 1 year after surgery.

Study Overview

• Status: Active, not recruiting
• Conditions: Colorectal Cancer Metastatic; Colorectal Cancer Stage IV; Appendix Cancer; Colorectal Cancer, Genetics of
• Intervention / Treatment: Diagnostic test: prospective single arm biomarker (plasma cell-free DNA hydroxymethylation) study

Detailed Description

This will be a prospective single arm biomarker (plasma-free DNA 5-hydroxymethylation) study. Fifty-five Adult patients with peritoneal metastases of colorectal and appendiceal origin who are candidates for a curative surgery and fulfill the inclusion criteria will be offered to participate in this study. In addition to the postoperative standard of care oncological surveillance of these patients which includes periodic physical examinations, cross sectional imaging studies (CT or MRI) and blood work for conventional tumor markers, serial measurements of plasma hydroxymethylation signatures will be performed. We will use a model developed in a separate pilot study to identify recurrent peritoneal metastasis based on 5hmC signatures. As part of this study, blood collection for measurements of plasma hydroxymethylation signatures of target genes will be performed at seven time points:

• Just before surgery (During the preoperative clinic visit or at the operating room).
• 5-7 days after surgery (just before hospital discharge).
• 6 weeks after surgery (first postoperative clinic visit).
• 3 months after surgery (second postoperative clinic visit).
• 6 months after surgery (third postoperative clinic visit).
• 9 months after surgery (fourth postoperative clinic visit).
• 12 months after surgery (fifth postoperative clinic visit). Standard of care surveillance elements that include patient history and physical examination, conventional blood biomarkers (CEA, CA 19-9 and CA 125) and cross sectional imaging of the chest, abdomen and pelvis will be undertaken simultaneously at similar time points. We will then compare the sensitivities of DNA hydroxymethylation signatures and conventional blood biomarkers in diagnosing clinically detectable recurrence at 1 year after surgery. We hypothesize that plasma hydroxymethylation signatures have higher sensitivity in identifying clinically detectable recurrence when compared with conventional tumor markers (CEA, CA 19-9 and CA 125).

• Study Type: Observational
• Enrollment (Estimated): 55

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago

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

Adult patients with peritoneal metastasis of colorectal or high grade appendiceal origin who are candidates for cytoreductive surgery with hyperthermic intraperitoneal chemotherapy

Description

Inclusion Criteria:

I. Histologic proof of colorectal adenocarcinoma or high grade appendiceal tumors (appendiceal adenocarcinoma or ex-goblet adenocarcinoma Tang B or C).

II. Age ≥ 18 years. III. Patients with known peritoneal metastasis (PM) who are candidates for complete cytoreduction and HIPEC. Known PM - diagnosed previously by diagnostic laparoscopy / laparotomy or clear radiological evidence of PM.

IV. Neoadjuvant chemotherapy permitted. V. The patient is able to provide informed consent. VI. The patient is planned to undergo his / her postoperative surveillance at UCM, as this study's protocol requires multiple clinic visits.

VII. No evidence of systemic metastasis.

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Exclusion Criteria:

Vulnerable subjects will not participate in this study.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
clinically detectable recurrence at 1 year after surgery.	Clear radiological evidence of recurrent disease.; Histopathological proof (by means of endoscopy, imaging guided biopsy or diagnostic surgery) of recurrent disease.; A new lesion revealed by physical examination	5 years

Collaborators and Investigators

• Sponsor: University of Chicago
• Investigators: Principal Investigator: Bruce Bissonnette, MD, University of Chicago

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2019
• Primary Completion (Estimated): October 31, 2025
• Study Completion (Estimated): October 31, 2025

Study Registration Dates

• First Submitted: November 6, 2019
• First Submitted That Met QC Criteria: November 6, 2019
• First Posted (Actual): November 8, 2019

Study Record Updates

• Last Update Posted (Actual): February 14, 2024
• Last Update Submitted That Met QC Criteria: February 12, 2024
• Last Verified: February 1, 2024

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; Cecal Diseases; Cecal Neoplasms; Colorectal Neoplasms; Appendiceal Neoplasms
• Other Study ID Numbers: IRB19-0913

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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