Anatomical Resection VS. Nonanatomical Resection for Colorectal Liver Metastases With Gene Mutation or Right-sidedness

Anatomical Resection Versus Nonanatomical Resection for Colorectal Liver Metastases Patients With Gene Mutation or Right-sidedness: The ARCLAMP Randomized Controlled Trial

In this study, colorectal cancer patients with initially resectable liver-only metastases, as prospectively confirmed by a local multidisciplinary team (MDT) according to predefined criteria, will be tested for RAS and BRAF tumor mutation status. Patients with gene mutant or right-sidedness will be randomised between anatomical resection (AR) or nonanatomical resection (NAR). The primary end-point is the relapse-free survival.

Study Overview

• Status: Not yet recruiting
• Conditions: Liver Metastases; Colorectal Carcinoma
• Intervention / Treatment: Procedure: anatomical liver resection; Procedure: nonanatomical liver resection

Detailed Description

This study is a prospective, single-center, randomized control trial. The major including criteria are (1) Histologically confirmed colorectal cancer initially resectable liver-only metastases ; (2) patient has the opportunity to perform either anatomical resection (AR) or nonanatomical resection (NAR) surgery; (3) the number of metastasis is 1-3; (4) KRAS/NRAS/BRAF mutation or right-sidedness. Patients will be randomised between AR or NAR. Patients will be stratified for gene mutation and right-sidedness.

Based upon the segmental anatomy of the liver according to Couinaud system, AR is defined as the resection of one or more complete hepatic segments in our study, including bisegmentectomy, right hemihepatectomy, left hemihepatectomy, extended right hemihepatectomy, extended left hemihepatectomy, single segmentectomy, caudate lobectomy, or a combination thereof. NAR, also called as wedge resection, is defined as the resection of the tumor with a margin of normal parenchyma regardless of the hepatic anatomy.

The primary end-point is the relapse-free survival. The secondary end-points are postoperative complication, postoperative mortality, hospital length of stay, and overall survival.

• Study Type: Interventional
• Enrollment (Estimated): 176
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jianmin Xu, MD; Phone Number: 86-18917982975; Email: xujmin@aliyun.com
• Study Contact Backup: Name: Yijiao Chen, MD; Phone Number: 86-13636443958; Email: 13636443958@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Zhongshan Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age ≥ 18 and ≤ 75 years;
2. Histological proof of colorectal adenocarcinoma;
3. Resectable colorectal liver metastasis without detectable extrahepatic distant metastatic disease (determined by a local MDT);
4. Suitable for anatomical or nonanatomical liver resection (determined by a local MDT);
5. Number of metastasis is 1 to 3;
6. KRAS/NRAS/BRAF mutation or right-sidedness;
7. Performance Status (ECOG) 0~1;
8. Adequate hematological function: Neutrophils≥1.5 x109/l and platelet count≥100 x109/l; Hb ≥9g/dl (within 1 week prior to randomization);
9. Adequate liver and renal function: total bilirubin ≤2.0 mg/dl, serum transaminases ≤ 5x upper limit of normal(ULN), and serum creatinine ≤ 1.5x ULN and creatinine clearance ≥ 30 ml/min;
10. Written informed consent.

Exclusion Criteria:

1. Previous systemic treatment for metastatic disease;
2. Previous surgery for metastatic disease;
3. Extrahepatic metastases;
4. Unresectable primary tumor;
5. Major cardiovascular events (myocardial infarction, severe/unstable angina, congestive heart failure, CVA) within 12 months before randomisation;
6. Second primary malignancy within the past 5 years;
7. Acute or subacute intestinal obstruction;
8. Drug or alcohol abuse;
9. No legal capacity or limited legal capacity;
10. Pregnant or lactating women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: anatomical resection group; Based upon the segmental anatomy of the liver according to Couinaud system, anatomical resection (AR) is defined as the resection of one or more complete hepatic segments in our study, including bisegmentectomy, right hemihepatectomy, left hemihepatectomy, extended right hemihepatectomy, extended left hemihepatectomy, single segmentectomy, caudate lobectomy, or a combination thereof.	Procedure: anatomical liver resection; Based upon the segmental anatomy of the liver according to Couinaud system, anatomical resection (AR) was defined as resection of 1 or more complete hepatic segments in our study, including bisegmentectomy, right hemihepatectomy, left hemihepatectomy, extended right hemihepatectomy, extended left hemihepatectomy, single segmentectomy, caudate lobectomy, or a combination of these.
Active Comparator: nonanatomical resection group; nonanatomical resection (NAR), also called as wedge resection, is defined as the resection of the tumor with a margin of normal parenchyma regardless of the hepatic anatomy.	Procedure: nonanatomical liver resection; Nonanatomical resection(NAR), known as wedge resection, was defined as resection of the tumor with a margin of normal parenchyma without regard to hepatic anatomy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
relapse-free survival	The relapse-free survival (PFS) was defined as the period from the start of initial liver resection to the date of tumor relapse or death	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
postoperative hospital stay	The postoperative hospital stay is defined as the number of date from the first day after operation to discharge.	30 days post operatively
postoperative complication	Patients will be evaluated for surgical morbidity during 1 month. Postoperative morbidity will be scored according 'Clavien-Dindo Grade'.	After surgery during one month
overall survival	The overall survival (OS) was defined as the period from the start of initial liver resection until death from any cause, at which point the data was censored.	5 years
postoperative mortality	any death occured within 90 days after the last resection of primary and metastatic lesions	After surgery during 90 days

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Principal Investigator: Jianmin Xu, MD, Fudan University

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2023
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: May 15, 2023
• First Submitted That Met QC Criteria: May 21, 2023
• First Posted (Actual): May 31, 2023

Study Record Updates

• Last Update Posted (Actual): May 31, 2023
• Last Update Submitted That Met QC Criteria: May 21, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• 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; Hematinics; Liver Extracts
• Other Study ID Numbers: ARCLAMP

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