Predictive Value of Postoperative Circulating Tumor DNA Monitoring for Colorectal Cancer Recurrence

The Predictive Value of Postoperative Circulating Tumor DNA Monitoring in Assessing the Risk of Recurrence in Stage I-IV Colorectal Cancer Patients, An Observational Study

This observational study aims to assess the predictive value of postoperative circulating tumor DNA (ctDNA) monitoring in evaluating the risk of recurrence in stage I-IV colorectal cancer patients. The study involves the collection of blood samples from patients who have undergone surgery for colorectal cancer. Sensitivity-enhanced molecular biology techniques are utilized to detect ctDNA in these samples. The correlation between ctDNA detection and the risk of recurrence is evaluated by analyzing patient follow-up data and clinical information. The findings of this study may contribute to the development of improved postoperative management strategies, such as identifying high-risk individuals and implementing additional treatment measures to reduce the risk of recurrence.

Study Overview

• Status: Active, not recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Other: Serial ctDNA monitoring

• Study Type: Observational
• Enrollment (Estimated): 220

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun yat-sen University Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Stage I-IV colorectal cancer with curative intent.

Description

Inclusion Criteria:

1. Age ≥ 18 years at the time of signing the informed consent form.
2. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0-1.
3. Histologically confirmed colorectal cancer located from the ileocecal junction to the rectosigmoid junction, with a distance of >15cm from the anal verge. Regardless of mismatch repair (MMR) status, Rat sarcoma (RAS) gene and proto-oncogene serine/threonine-protein kinase (RAF) gene status.
4. Pathologically or cytologically confirmed American Joint Committee on Cancer (AJCC) tumor node metastasis (TNM) stage I-IV colorectal cancer patients (8th edition).
5. No evidence of distant metastasis confirmed by comprehensive examination (no distant organ or lymph node metastasis).

6. Normal organ function, as indicated by the following criteria:

   • Hematology criteria: For patients who have not received blood transfusion, white blood cell (WBC) ≥ 3.5/4.0 × 10^9/L, neutrophils ≥ 1.5 × 10^9/L, platelet (PLT) ≥ 100 × 10^9/L.
   • Biochemistry criteria: Crea and bilirubin (BIL) ≤ 1.0 times the upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times ULN, alkaline phosphatase (ALP) ≤ 2.5 × ULN, total bilirubin (Tbil) ≤ 1.5 × ULN.
7. Ability to provide clinical data required for the study.
8. Sufficient tumor tissue available for analysis.
9. Patients capable of achieving R0 radical resection.
10. Patients capable of adhering to the planned schedule, actively participating in regular clinical follow-up, and necessary treatments.

Exclusion Criteria:

1. History of concurrent or prior malignancies (excluding adequately treated cervical carcinoma in situ, basal cell carcinoma, or squamous cell carcinoma of the skin).
2. Patients who have received neoadjuvant therapy.
3. Patients with other severe diseases that may affect follow-up and short-term survival, as determined by the investigator.
4. Any other medical, social, or psychological conditions that, in the opinion of the investigator, would make the patient unsuitable for participation in this study.
5. Inability to undergo clinical follow-up using contrast-enhanced magnetic resonance imaging (MRI) or contrast-enhanced computed tomography (CT).

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort; Patients with stage I to IV colorectal cancer	Other: Serial ctDNA monitoring; Baseline blood samples, surgical resected tumor tissue, blood samples after surgery (D5-7), blood samples before adjuvant therapy and blood samples after adjuvant therapy (every 3 months for up to 2 years follow-up) will be collected from colorectal patients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-year recurrence free survival rate of the cohort evaluated by ctDNA	To evaluate the correlation between circulating tumor DNA (ctDNA) detection and recurrence-free survival.	2 years post surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time point of ctDNA MRD test for recurrence monitoring	To assess time from positive ctDNA test to clinical recurrence.	Within 4-6 week post operation
The ctDNA positive rate in stage III colorectal cancer	To assess positive rate of ctDNA minimal residual disease (MRD) test in stage III of colorectal cancer patient after surgery.	Within 4-6 week post operation

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: Guangzhou Burning Rock Dx Co., Ltd.
• Investigators: Principal Investigator: Gong Chen, PhD, Sun Yat-sen University

Publications and helpful links

General Publications

• Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12. Erratum In: CA Cancer J Clin. 2020 Jul;70(4):313.
• Reinert T, Henriksen TV, Christensen E, Sharma S, Salari R, Sethi H, Knudsen M, Nordentoft I, Wu HT, Tin AS, Heilskov Rasmussen M, Vang S, Shchegrova S, Frydendahl Boll Johansen A, Srinivasan R, Assaf Z, Balcioglu M, Olson A, Dashner S, Hafez D, Navarro S, Goel S, Rabinowitz M, Billings P, Sigurjonsson S, Dyrskjot L, Swenerton R, Aleshin A, Laurberg S, Husted Madsen A, Kannerup AS, Stribolt K, Palmelund Krag S, Iversen LH, Gotschalck Sunesen K, Lin CJ, Zimmermann BG, Lindbjerg Andersen C. Analysis of Plasma Cell-Free DNA by Ultradeep Sequencing in Patients With Stages I to III Colorectal Cancer. JAMA Oncol. 2019 Aug 1;5(8):1124-1131. doi: 10.1001/jamaoncol.2019.0528. Erratum In: JAMA Oncol. 2019 Jun 13;:
• Siegel RL, Miller KD, Goding Sauer A, Fedewa SA, Butterly LF, Anderson JC, Cercek A, Smith RA, Jemal A. Colorectal cancer statistics, 2020. CA Cancer J Clin. 2020 May;70(3):145-164. doi: 10.3322/caac.21601. Epub 2020 Mar 5.
• Govindarajan A, Fraser N, Cranford V, Wirtzfeld D, Gallinger S, Law CH, Smith AJ, Gagliardi AR. Predictors of multivisceral resection in patients with locally advanced colorectal cancer. Ann Surg Oncol. 2008 Jul;15(7):1923-30. doi: 10.1245/s10434-008-9930-1. Epub 2008 May 13.

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2022
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: November 16, 2023
• First Submitted That Met QC Criteria: November 16, 2023
• First Posted (Actual): November 22, 2023

Study Record Updates

• Last Update Posted (Actual): December 4, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: recurrence; circulating tumor DNA
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Disease Attributes; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Recurrence
• Other Study ID Numbers: pilotCRC-MRD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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