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

Colorectal Cancer Metastatic Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04157322
• Other study ID #: IRB19-0913
• Status: Active, not recruiting
• Start date: August 26, 2019
• Est. completion date: October 31, 2025

Study information

• Verified date: February 2024
• Source: University of Chicago
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 55
• Est. completion date: October 31, 2025
• Est. primary completion date: October 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Appendiceal Neoplasms
• Appendix Cancer
• Colorectal Cancer Metastatic
• Colorectal Cancer Stage IV
• Colorectal Cancer, Genetics of
• Colorectal Neoplasms

Intervention

Diagnostic Test:
• prospective single arm biomarker (plasma cell-free DNA hydroxymethylation) study
Blood draw

Locations

Country	Name	City	State
United States	The University of Chicago	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
University of Chicago

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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