Clinical trial NCT04157322: Plasma 5hmC Signatures as a Marker of Colorectal / Appendiceal Peritoneal Metastasis
Official title: 5-hydroxymethylation Signatures in Plasma Circulating Cell-free DNA as Markers for Tumor Burden and Recurrence in Appendiceal and Colorectal Peritoneal Metastasis
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Colorectal Cancer Stage IV
Colorectal Cancer Metastatic
Colorectal Cancer, Genetics of
Appendix Cancer
Lead sponsor: University of Chicago
Sponsor class: OTHER
First posted: 2019-11-08
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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

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.

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).

Eligibility criteria: 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.

Primary outcomes:
measure: clinically detectable recurrence at 1 year after surgery.
timeFrame: 5 years
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: The University of Chicago
state: Illinois
Study officials:
affiliation: University of Chicago
name: Bruce Bissonnette, MD
role: PRINCIPAL_INVESTIGATOR
References: