Ablation vs Resection of Colorectal Cancer Liver Metastases (NEW-COMET)

A Randomized Controlled Trial of Needle Ablation With 3D Verification vs Surgical Resection of Colorectal Cancer Liver Metastases

230 patients with colorectal cancer liver metastases will be randomly assigned to resection or thermal ablation.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer Metastatic
• Intervention / Treatment: Procedure: Surgical resection; Procedure: Thermal ablation

Detailed Description

Rationale: The use of thermal ablation of liver tumors is rapidly increasing. This is despite a lack of high-level evidence of the oncologic efficacy of ablation. Ablation is most often used in cases where resection is not possible, but as the technique has improved it is increasingly used as a substitute for resection. A majority of studies on ablation are hampered by selection bias. Selection bias can only be overcome in a randomized controlled trial.

Primary objective:

To compare rates of local tumor progression within 12 months in patients randomly assigned to thermal ablation or surgical resection of colorectal liver metastases.

Secondary objectives:

• To establish a pipeline for immediate three-dimensional verification of the ablated zone following thermal ablation of liver metastases.
• To compare health related quality of life in patients randomly assigned to thermal ablation or surgical resection of colorectal liver metastases.
• To perform a cost-effectiveness analysis (Cost per quality adjusted life year) of thermal ablation and resection of colorectal liver metastases.
• To compare disease-free and overall survival in in patients randomly assigned to thermal ablation or surgical resection of colorectal liver metastases.
• To evaluate the hemodynamic response to thermal ablation and laparoscopic resection of liver tumors.

Study design:

A randomized, controlled, multicenter, double-blinded non-inferiority trial.

Study population:

Two groups of 115 patients (230 in total) with colorectal liver metastasis eligible for radical treatment using EITHER resection OR ablation (not a combination).

Intervention:

Ablation of colorectal liver metastases

Control:

Resection of colorectal liver metastases

Main study parameters/endpoints:

The primary endpoint of the study is local recurrence of cancer at 12 months. Secondary endpoints include overall survival, disease free survival, health related quality of life, postoperative pain, complications, hospital stay and cost-effectiveness.

• Study Type: Interventional
• Enrollment (Estimated): 230
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Åsmund A Fretland, MD PhD; Phone Number: 004723070100; Email: aasmund@fretland.no
• Study Contact Backup: Name: Bjørn Edwin, Professor; Phone Number: 004793008635; Email: bjoedw@ous-hf.no

Study Locations

• Norway
  • Oslo, Norway, 0424
    • Recruiting
    • Oslo University Hospital, Department of Gastrointestinal surgery, The National Hospital
    • Contact: Marianne Moe, Head nurse; Phone Number: +4723070000

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically verified colorectal cancer
• Colorectal liver metastases (proven or suspected) eligible for radical treatment using EITHER resection OR ablation (not a combination), as decided by the liver MDT meeting at the study center
• The patient is fit to undergo both resection and ablation of all liver metastases
• Size of largest lesion up to and including 30 mm
• In case of solitary metastasis, resection plan includes resection of ≤ 2 anatomical segments.
• In case of multiple metastases in one continuous resection, resection plan can include ≤ 4 anatomical segments (including hemihepatectomy)
• ≤ 5 tumors to be treated in one procedure
• Primary tumor either resected (primary first) or with a plan for curative treatment (liver first).

Exclusion Criteria:

• More than 3 lung metastases where 1 is >10mm, or 1 lung metastasis >15 mm (OR: unresectable lung metastases as decided by the lung MDT meeting)

• Presence of extrahepatic, extrapulmonary metastases.
• Surgical indication for removal of enlarged lymph nodes in the hepatic hilum. (Enlarged lymph nodes without indication of removal are not considered an exclusion criterium)
• Tumor closer than 10 mm to right/left main bile duct
• Suspected tumor infiltration to adjacent organs
• Progression (as of RECIST [18]) on 2nd line chemotherapy
• Previous inclusion in this trial
• Not eligible for workup according to study criteria
• Contraindication to contrast enhanced CT scan
• Manifest liver cirrhosis
• Pregnancy
• ECOG performance status ≥3
• Simultaneous resection of primary tumor or any other concomitant surgical procedure
• Any other reason why, in the investigator's opinion, the patient should not be included.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Surgical resection; Liver resection	Procedure: Surgical resection; Resection of metastasis
Experimental: Thermal ablation; Thermal ablation (Microwave or radiofrequency)	Procedure: Thermal ablation; Ablation of metastasis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local tumor progression	Local tumor progression at site of treatment	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival following treatment	60 months
Overall survival (secondary analysis)	A secondary analysis will be performed on a oncologically more homogenous group of patients that fulfil the following requirements: a) no previous surgical procedure on the liver, b) no extrahepatic metastases, and c) that had their primary tumor resected	60 months
Disease free survival	DFS	60 months
Postoperative complications	Morbidity	30 days
Health related quality of life	HRQoL is measured using SF-36	12 months
Cost-Effectiveness	An analysis of cost will be performed to assess cost-effectiveness	12 months
Hemodynamic response	The hemodynamic response to the two interventions will be recorded and compared	7 days
Ventilation methods	The intraoperative movement of the liver will be measured using different ventilation methods (one lung ventilation, jet ventilation, gentle double lung ventilation). The movement of the liver during the different ventilation methods will be assessed in cm.	1 day
Cerebral flow	Intraoperative cerebral blood flow will be measured and related to cardiac output and other hemodynamic measures. Micro bubbles caused by the treatment will be visualized using ultrasonography.	1 day
Inflammatory response	The inflammatory response (cytokines, complement, catecholamines) will be compared.	7 days

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Investigators: Study Director: Bjørn Edwin, Professor, Head of clinical research, The Intervention Centre, Oslo University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2021
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: November 2, 2021
• First Submitted That Met QC Criteria: November 18, 2021
• First Posted (Actual): November 22, 2021

Study Record Updates

• Last Update Posted (Estimated): December 19, 2023
• Last Update Submitted That Met QC Criteria: December 12, 2023
• Last Verified: December 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
• Other Study ID Numbers: REK255384

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD maybe shared pending approval from local data protection officer
• IPD Sharing Time Frame: 3-5 years
• IPD Sharing Access Criteria: Upon contact to PI
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No