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

• ClinicalTrials.gov Identifier: NCT05129787
• Recruitment Status: Recruiting
• First Posted: November 22, 2021
• Last Update Posted: December 19, 2023
• Sponsor: Oslo University Hospital
• Information provided by (Responsible Party): Åsmund Avdem Fretland, Oslo University Hospital

Tracking Information

• First Submitted Date: November 2, 2021
• First Posted Date: November 22, 2021
• Last Update Posted Date: December 19, 2023
• Actual Study Start Date: December 16, 2021
• Estimated Primary Completion Date: December 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 18, 2021)

Local tumor progression [ Time Frame: 12 months ]

Local tumor progression at site of treatment

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 12, 2023)

• Overall survival [ Time Frame: 60 months ]
  Overall survival following treatment
• Overall survival (secondary analysis) [ Time Frame: 60 months ]
  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
• Disease free survival [ Time Frame: 60 months ]
  DFS
• Postoperative complications [ Time Frame: 30 days ]
  Morbidity
• Health related quality of life [ Time Frame: 12 months ]
  HRQoL is measured using SF-36
• Cost-Effectiveness [ Time Frame: 12 months ]
  An analysis of cost will be performed to assess cost-effectiveness
• Hemodynamic response [ Time Frame: 7 days ]
  The hemodynamic response to the two interventions will be recorded and compared
• Ventilation methods [ Time Frame: 1 day ]
  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.
• Cerebral flow [ Time Frame: 1 day ]
  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.
• Inflammatory response [ Time Frame: 7 days ]
  The inflammatory response (cytokines, complement, catecholamines) will be compared.

Original Secondary Outcome Measures (submitted: November 18, 2021)

• Overall survival [ Time Frame: 60 months ]
  Overall survival following treatment
• Overall survival (secondary analysis) [ Time Frame: 60 months ]
  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
• Disease free survival [ Time Frame: 60 months ]
  DFS
• Postoperative complications [ Time Frame: 30 days ]
  Morbidity
• Health related quality of life [ Time Frame: 12 months ]
  HRQoL is measured using SF-36
• Cost-Effectiveness [ Time Frame: 12 months ]
  An analysis of cost will be performed to assess cost-effectiveness

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Ablation vs Resection of Colorectal Cancer Liver Metastases
• Official Title: A Randomized Controlled Trial of Needle Ablation With 3D Verification vs Surgical Resection of Colorectal Cancer Liver Metastases
• Brief Summary: 230 patients with colorectal cancer liver metastases will be randomly assigned to resection or 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
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Masking Description:

Masking will be performed by large drapings on wounds and masking of operation notes

Primary Purpose: Treatment

• Condition: Colorectal Cancer Metastatic

Intervention

• Procedure: Surgical resection
  Resection of metastasis
• Procedure: Thermal ablation
  Ablation of metastasis

Study Arms

• Active Comparator: Surgical resection
  Liver resection
  Intervention: Procedure: Surgical resection
• Experimental: Thermal ablation
  Thermal ablation (Microwave or radiofrequency)
  Intervention: Procedure: Thermal ablation

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 18, 2021): 230
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2025
• Estimated Primary Completion Date: December 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Åsmund A Fretland, MD PhD; 004723070100; aasmund@fretland.no

Contact: Bjørn Edwin, Professor; 004793008635; bjoedw@ous-hf.no

• Listed Location Countries: Norway

Administrative Information

• NCT Number: NCT05129787
• Other Study ID Numbers: REK255384
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: IPD maybe shared pending approval from local data protection officer
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Supporting Materials: Analytic Code
• Time Frame: 3-5 years
• Access Criteria: Upon contact to PI

• Current Responsible Party: Åsmund Avdem Fretland, Oslo University Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Oslo University Hospital
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Oslo University Hospital
• Verification Date: December 2023