ctDNA-guided Adjuvant Chemotherapy in Liver Metastasis of Colorectal Cancer

ctDNA-guided Adjuvant Chemotherapy in Liver Metastasis of Colorectal Cancer: A Prospective Multicenter Randomized Controlled Clinical Trial

The goal of this clinical trial is to compare in resectable colorectal cancer liver metastasis patients.The main question it aims to answer is whether the 3-year progression-free survival rate (PFS) of "watching and waiting" is non-inferior to adjuvant chemotherapy in postoperative ctDNA-negative resectable colorectal cancer liver metastasis patients.Participants will undergo ctDNA testing after resection of colorectal cancer liver metastasis, and will be randomly assigned to receive adjuvant chemotherapy or "watching and waiting" treatment strategy. The researchers will compare the outcomes between the two groups to see if the PFS between the two groups is similar.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; Chemotherapy Effect; Liver Metastases; Circulating Tumor Cell
• Intervention / Treatment: Drug: FOLFOX chemotherapy regimen; Procedure: Colorectal cancer resection combined with liver metastasis resection.

• Study Type: Interventional
• Enrollment (Anticipated): 490
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • GuangZhou, Guangdong, China
      • Recruiting
      • The Sixth Affiliate Hospital of Sun Yat-Sen University
      • Contact: Yaoyi Huang, BS; Phone Number: 86-15986423743; Email: huangyy355@mail2.sysu.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Both genders are eligible; aged between 18-75 years old; have received neoadjuvant chemotherapy;
2. Patients with liver metastatic colorectal cancer who have achieved R0 resection according to MDT evaluation (including patients with metastases treated with ablation therapy that achieved similar R0 resection effects);
3. Patients with negative ctDNA after surgery;
4. ASA grade <IV and/or ECOG performance status score ≤ 2;
5. Have sufficient understanding of the study and voluntarily sign an informed consent form.

Exclusion Criteria:

1. Patients with distant metastases, including pelvic, ovarian, peritoneal, etc.;
2. Patients with a history of other malignancies;
3. Patients with severe liver, kidney, heart and lung dysfunction, coagulation dysfunction, or serious underlying diseases who cannot tolerate chemotherapy;
4. Patients who are allergic to any component in the study;
5. Patients who have received other tumor-related investigational drug therapy;
6. Patients with severe uncontrolled recurrent infections or other serious uncontrolled concurrent diseases;
7. Patients with other factors that may affect the study results or lead to premature termination of the study, such as alcoholism, drug abuse, other serious diseases that require comprehensive treatment (including mental disorders), and serious abnormal laboratory tests;
8. Patients with a history of severe mental illness;
9. Pregnant or lactating women;
10. Patients with other clinical or laboratory conditions that the investigator deems unsuitable for participation in the trial.

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: Watching and waiting group; Watch and Wait strategy is one of the treatment strategies of advanced rectal cancer, which recommends no immediate surgery with close surveillance.	Procedure: Colorectal cancer resection combined with liver metastasis resection.; The preferred surgical approach is resection of the corresponding colon segment with regional lymph node dissection. If conditions permit, synchronous resection of the primary lesion and liver metastases of colorectal cancer can be performed to achieve curative resection.
Active Comparator: Adjuvant chemotherapy group; Chemotherapy regimens recommended include oxaliplatin-based CapeOx or FOLFOX regimens, or single-agent 5-FU/LV, capecitabine, or combination with targeted therapy.	Drug: FOLFOX chemotherapy regimen; Chemotherapy regimens recommended include oxaliplatin-based CapeOx or FOLFOX regimens, or single-agent 5-FU/LV, capecitabine, or combination with targeted therapy.; Other Names: CapeOx chemotherapy regimen; Procedure: Colorectal cancer resection combined with liver metastasis resection.; The preferred surgical approach is resection of the corresponding colon segment with regional lymph node dissection. If conditions permit, synchronous resection of the primary lesion and liver metastases of colorectal cancer can be performed to achieve curative resection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3-year progression-free survival	PFS is defined as the time from randomization to the occurrence of any progression or death from any cause.	3 years after operation.
5-year progression-free survival	PFS is defined as the time from randomization to the occurrence of any progression or death from any cause.	5 years after operation.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3-year overall survival	Overall survival is defined as the time from randomization to death from any cause. For patients who are still alive at the time of the final analysis, the date of the last contact will be recorded.	3 years after operation.
3-year overall survival	Overall survival is defined as the time from randomization to death from any cause. For patients who are still alive at the time of the final analysis, the date of the last contact will be recorded.	5 years after operation.
Complications	When evaluating the safety and tolerability of adjuvant therapy, researchers typically assess adverse events (AEs) based on their incidence and severity, and then grade them according to the NCI CTCAE version 5.0. NCI CTCAE 5.0 categorizes AEs into 5 grades based on severity, including grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (life-threatening), and grade 5 (death).	5 years.

Collaborators and Investigators

• Sponsor: Sixth Affiliated Hospital, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2023
• Primary Completion (Anticipated): February 20, 2031
• Study Completion (Anticipated): February 20, 2033

Study Registration Dates

• First Submitted: March 20, 2023
• First Submitted That Met QC Criteria: April 14, 2023
• First Posted (Actual): April 18, 2023

Study Record Updates

• Last Update Posted (Actual): April 18, 2023
• Last Update Submitted That Met QC Criteria: April 14, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Colorectal Cancer; Circulating Tumor DNA; Liver Metastases
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Liver Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplastic Processes; Colorectal Neoplasms; Neoplasm Metastasis; Liver Neoplasms; Neoplastic Cells, Circulating
• Other Study ID Numbers: 1010(CG)2022-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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