CAPEOX vs Observation in Colorectal Cancer Patients With Positive MRD

A Randomized Controlled Trial of CAPEOX vs Observation in Early-stage Colorectal Cancer Patients With Positive MRD After Curative Surgery

Patients with stage Ⅰ colorectal cancer or stage Ⅱ colon cancer usually have a good prognosis and are not recommended to receive adjuvant chemotherapy after radical surgery. With the advances in liquid biopsy technology, detection of circulating tumor DNA (ctDNA) can effectively identify early-stage cancer patients with minimal residual disease (MRD) after surgery. According to the growing number of MRD studies in solid tumor, colorectal cancer patients with ctDNA-MRD detection have a poor clinical outcome and are likely to relapse within two years. This study aims to assess the efficacy of adjuvant chemotherapy with capecitabine plus oxaliplatin (CAPEOX) compared with conventional observation in MRD-positive patients with stage I colorectal cancer and clinically low-risk stage II colon cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Capecitabine tablets; Drug: Oxaliplatin

• Study Type: Interventional
• Enrollment (Anticipated): 38
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Kefeng Ding, MD, PhD; Phone Number: +8687784720; Email: dingkefeng@zju.edu.cn
• Study Contact Backup: Name: Qian Xiao, MD, PhD; Email: qxiao3@zju.edu.cn

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200433
      • Changhai Hospital of Shanghai
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310016
      • Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
    • Hangzhou, Zhejiang, China, 310999
      • Second Affiliated Hospital Zhejiang University College of Medicine
    • Ningbo, Zhejiang, China, 315010
      • The second hospital of Ningbo City

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Colorectal cancer confirmed by pathology, and the TNM stage (AJCC v8) is stage I or stage II. Stage II patients have T3 colonic adenocarcinoma with proficient mismatch-repair system (by immunohistochemistry for four mismatch repair proteins MSH1, MSH2, MSH6, and PMS2) and have no the following clinical risk factors: a) less than 12 lymph nodes examined; b) mucinous carcinoma; c) poor differentiation; d) bowel obstruction or perforation; e) lymphatic/vascular invasion, perineural invasion; f) close, indeterminate, uncertain, positive margins
2. ECOG performance status 0-1
3. No neoadjuvant therapy before surgery
4. Appropriate for active surveillance (i.e., no adjuvant chemotherapy) based on current practice patterns or according to the Chinese Society of Clinical Oncology guidelines for Colorectal Cancer (version 2022)
5. No history of other primary cancers in the past 3 years
6. No history of bone marrow, stem cell or organ transplant
7. Blood samples from 7 to 21 days after surgery were tested positive for ctDNA (tested by MinerVa MRD assay)
8. Pregnancy test done within 14 days before randomization must be negative (for women of childbearing potential only)
9. Voluntarily join the study and sign the informed consent document
10. No unstable or any medical condition that affects patient safety and study compliance evaluated by researchers
11. Availability and provision of adequate surgical tumor tissue for molecular diagnostics

Exclusion Criteria:

1. Patients with multiple primary colorectal cancers
2. Patients with another primary cancer

3. Patients have the following conditions by blood test, or have obvious contraindication in adjuvant chemotherapy:

   1. Moderate/severe renal impairment (GFR<30 ml/min), as calculated by the Cockcroft and Gault equation
   2. Absolute neutrophil count <1.5×109/L
   3. Platelet count < 75×109/L
   4. Hemoglobin <90 g/L
   5. Aspartate aminotransferase/Alanine aminotransferase >2.5 × upper limit of normal
4. Lactating women
5. Have serious or uncontrolled medical condition that may preclude compliance with the protocol

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CAPEOX; Drug CAPEOX (Oxaliplatin 130 mg/m2 IV day 1, Capecitabine 1000 mg/m2, twice daily PO for 14 days, repeat every 3 weeks) for at most 8 cycles.	Drug: Capecitabine tablets; Capecitabine 1000 mg/m2, twice daily PO for 14 days, repeat every 3 weeks, for at most 8 cycles.; Drug: Oxaliplatin; Oxaliplatin 130 mg/m2 IV day 1, combined with Capecitabine, for at most 8 cycles.
No Intervention: Observation; Patients undergo active surveillance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Recurrence-free survival	18 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Clearance of circulating tumor DNA (ctDNA)	6 months

Collaborators and Investigators

• Sponsor: Zhejiang University
• Collaborators: GeneCast Biotechnology Co., Ltd.
• Investigators: Principal Investigator: Kefeng Ding, MD, PhD, Second Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2023
• Primary Completion (Anticipated): September 1, 2026
• Study Completion (Anticipated): December 1, 2026

Study Registration Dates

• First Submitted: January 16, 2023
• First Submitted That Met QC Criteria: January 16, 2023
• First Posted (Estimate): January 26, 2023

Study Record Updates

• Last Update Posted (Estimate): January 26, 2023
• Last Update Submitted That Met QC Criteria: January 16, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Capecitabine; Oxaliplatin
• Other Study ID Numbers: IR2022577

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