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

• Sponsor: University of Chicago (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04157322
• Collaborator: (none)
• Enrollment: 55
• Location: 1
• Anticipated Duration (Months): 74.2
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer Stage IV; Colorectal Cancer Metastatic; Colorectal Cancer, Genetics of; Appendix Cancer	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 Design

• Study Type: Observational
• Anticipated Enrollment: 55 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: 5-hydroxymethylation Signatures in Plasma Circulating Cell-free DNA as Markers for Tumor Burden and Recurrence in Appendiceal and Colorectal Peritoneal Metastasis
• Actual Study Start Date: Aug 26, 2019
• Anticipated Primary Completion Date: Oct 31, 2021
• Anticipated Study Completion Date: Oct 31, 2025

Outcome Measures

Primary Outcome Measures

1. clinically detectable recurrence at 1 year after surgery. [5 years]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

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

2. 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.

3. Neoadjuvant chemotherapy permitted. V. The patient is able to provide informed consent.

4. The patient is planned to undergo his / her postoperative surveillance at UCM, as this study's protocol requires multiple clinic visits.

5. No evidence of systemic metastasis.

Exclusion Criteria:

Vulnerable subjects will not participate in this study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The University of Chicago	Chicago	Illinois	United States	60637

Sponsors and Collaborators

• University of Chicago

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Chicago
• ClinicalTrials.gov Identifier: NCT04157322
• Other Study ID Numbers: IRB19-0913
• First Posted: Nov 8, 2019
• Last Update Posted: Nov 8, 2019
• Last Verified: Nov 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Colorectal Neoplasms; Appendiceal Neoplasms

Study Results

No Results Posted as of Nov 8, 2019