ctDNA as a Assisted Diagnosis, Early Intervention and Prognostic Marker for Peritoneal Metastases From Colorectal Cancer

Study Overview
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Brief Summary
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This is a prospective, open-label, randomized controlled clinical trial, by monitoring the serum ctDNA mutational profile using NGS, aiming to elucidate the correlation between the postoperative ctDNA status and the assisted diagnosis, early intervention and prognosis for colorectal cancer peritoneal metastases.

Official Title
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Circulating Tumor DNA (ctDNA) as a Assisted Diagnosis, Early Intervention and Prognostic Marker for Peritoneal Metastases From Colorectal Cancer: A Prospective, Open-label, Randomized Controlled Study

Conditions
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Colorectal Cancer, Peritoneal Metastases

Intervention / Treatment
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* Diagnostic Test: ctDNA monitoring
* Diagnostic Test: Imageology


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must be a man or woman of at 18-75; Patients must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-21； Patients with primary colorectal cancer proven by pathology； Patients with high risk factors for peritoneal metastasis (simultaneous peritoneal metastasis, ovarian metastasis, PT4, CT4, tumor perforation, tumor-complete intestinal obstruction, mucinous adenocarcinoma/signet ring cell carcinoma of PT3, positive surgical margin, and tumor rupture and hemorrhage); 6-12 months after colorectal cancer radical surgery, patients who have two consecutive positive ctDNA tests within one month; Patients who have finished standard adjuvant therapy after surgery; (Choose 5-FU or 5-FU analog-based chemotherapy regimen, and the perioperative chemotherapy should not exceed 6 months)； Patients who are negative of recurrence or metastasis in conventional oncology examination (serology, endoscopy, imaging) ; Written informed consent must be obtained from patients and ability for patients to comply with the requirements of the study. Exclusion Criteria: Patients who were diagnosed with other malignant tumors within 2 years before diagnosis of colorectal cancer; ASA class Ⅳ to Ⅴ; Patients who have other existence of distant metastasis outside the abdomen; Patients with serious mental illness; Patients with severe cardiovascular disease, uncontrollable infections, or other uncontrollable co-diseases; Patients who cannot be followed up as scheduled; Patients who participated in other clinical studies within 3 months prior to the trial; Pregnant or nursing women, men or women of childbearing potential who are unwilling to employ adequate contraception.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ctDNA monitoring<br>ctDNA monitoring will be performed at protocol-specified intervals and requirement | Diagnostic Test: ctDNA monitoring<br>* Patients who undergoing radical surgery for colorectal cancer for 6 12 months and with 2 consecutive positive ctDNA testing results within 1 month will be enrolled, and diagnostic laparoscopy will be performed immediately after enrollment. Patients with positive peritoneal metastasis (PCI score <20) will be treated with CRS+HIPEC. Tumor markers, endoscopic and imaging examinations, and ctDNA monitoring will be performed every 3 months in patients with negative peritoneal metastasis. Laparoscopy will be performed when imaging suggested peritoneal metastasis (oligometastases). Re-diagnostic laparoscopy will be performed 24 months after radical surgery when there is no radiographic evidence of recurrence or metastasis. Follow-up time will up to 36 months after colorectal cancer surgery.<br>|
| Active Comparator: Imageology (SOC)<br>Imaging examination will be performed at protocol-specified intervals and requirement | Diagnostic Test: Imageology<br>* Patients who undergoing radical surgery for colorectal cancer for 6 12 months and with 2 consecutive positive ctDNA testing results within 1 month will be enrolled. and there will be no need to conduct endoscopic exploration immediately after enrollment. Tumor markers, endoscopic and imaging examinations, and ctDNA monitoring will be performed every 3 months until imaging suggested peritoneal metastasis (oligometastases). Patients with positive peritoneal metastasis (PCI score <20) will be treated with CRS+HIPEC. Re-diagnostic laparoscopy will be performed 24 months after radical surgery when there is no radiographic evidence of recurrence or metastasis. Follow-up time will up to 36 months after colorectal cancer surgery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peritoneal Metastasis Free Survival (PMFS) | The survival rate without peritoneal metastasis (oligometastatic) at 24 months after radical resection of colorectal cancer. | Through study completion, up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detection Rate (DR) | DR of ctDNA monitoring for predicting peritoneal metastasis with abdominal exploration as the reference. DR of imageological examination for predicting peritoneal metastasis with abdominal exploration as the reference. DR of combination of ctDNA monitoring and imageological examination for predicting peritoneal metastasis with abdominal exploration as the reference. Will be compared in both arms. | Interim analyses: After 69 patients have been enrolled, up to 1.5 years | 
| Positive Percent Agreement (PPA) | PPA of ctDNA monitoring for predicting peritoneal metastasis with abdominal exploration as the reference. PPA of imageological examination for predicting peritoneal metastasis with abdominal exploration as the reference. PPA of combination of ctDNA monitoring and imageological examination for predicting peritoneal metastasis with abdominal exploration as the reference. Will be compared in both arms. | Interim analyses: After 69 patients have been enrolled, up to 1.5 years | 
| Negative Percent Agreement (NPA) | NPA of ctDNA monitoring for predicting peritoneal metastasis with abdominal exploration as the reference. NPA of imageological examination for predicting peritoneal metastasis with abdominal exploration as the reference. NPA of combination of ctDNA monitoring and imageological examination for predicting peritoneal metastasis with abdominal exploration as the reference. Will be compared in both arms. | Interim analyses: After 69 patients have been enrolled, up to 1.5 years | 
| The time of peritoneal metastasis diagnosed after radical surgery | Will be compared in both arms. | Interim analyses: After 69 patients have been enrolled, up to 1.5 years | 
| Peritoneal Cancer Index (PCI) Score | This scale measures the extent of peritoneal cancer throughout the peritoneal cavity. The range of this scale is from 0 to 39. 0 = no disease within the peritoneal cavity 0-9 = minimal disease 10-29 = moderate disease 30-39 = extensive disease Lower values are considered a better outcome for the patient. Will be compared in both arms. | Interim analyses: After 69 patients have been enrolled, up to 1.5 years | 
| Completeness of Cytoreduction (CC) Score | The degree to which the disease was able to be excised during the procedure. This scale ranges from CC0-CC3. CC0 = all disease has been cleared, with no visible peritoneal carcinomatosis after CRS CC1 = microscopic disease remains (Nodules persisting < 2.5 mm after CRS) CC2 = macroscopic disease remains (Nodules persisting between 2.5 mm and 2.5 cm) CC3 = Substantial Macroscopic disease remains (Nodules persisting > 2.5 cm) Lower values are considered a better outcome, with CC0/1 classed as favourable and CC2/3 indicating an incomplete clearance of disease. Will be compared in both arms. | Interim analyses: After 69 patients have been enrolled, up to 1.5 years | 
| The ctDNA clearance rate before and after CRS+HIPEC treatment | Will be compared in both arms. | Interim analyses: After 69 patients have been enrolled, up to 1.5 years | 
| The rate of Disease Free Survival (DFS) at 3 years after radical resection of colorectal cancer | Whether the patient is still alive and free of disease or not. Will be compared in both arms. | Through study completion, up to 3 years | 
| The Overall Survival (OS) at 3 years after radical resection of colorectal cancer | Whether the patient is still alive or not. Will be compared in both arms. | Through study completion, up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ctDNA