Improving Survival of COlorectal LIver Metastases by RFA-mediated Immunostimulation (ISCOLIM)

To examine radio frequency ablation as a treatment supplement to stimulate immunogenicity and improve survival for patients undergoing curative-intent surgery for colorectal liver metastases.

Study Overview

• Status: Recruiting
• Conditions: Liver Metastasis Colon Cancer
• Intervention / Treatment: Device: RFA (radiofrequency ablation)

Detailed Description

PURPOSE:

To investigate the impact of immunostimulation using radio frequency ablation (RFA) on survival in patients undergoing curative-intent surgery for colorectal liver metastases (CRLM).

HYPOTHESIS:

RFA-mediated partial destruction of CRLM will stimulate the immune system to recognize otherwise hidden cancer antigens, which in turn will improve survival by inhibiting micrometastases and recurrence.

BACKGROUND:

CRLM affects around 1,600 individuals in Denmark each year. State-of-the-art treatment includes liver resection, RFA treatment, radiation therapy, and chemotherapy. Of all individuals undergoing surgery, 50% will experience local or distant recurrence of the disease within five years. Although liver resection is the gold standard, RFA treatment has evolved considerably in recent years. RFA is a parenchymal-sparing treatment for hepatic malignancies, inducing a localized coagulation necrosis of the tumor. This leads to release of tumor antigens, which activates the patients' immune system. However, many cancer cells, including those from CRLM, have the ability to hide their antigens to the patients' immune systems. Using RFA as immunostimulation prior to surgery, these antigens may become visible to the immune system, which in turn can help eradicating all tumor cells and decrease the risk of tumor recurrence. Combined, this likely improves survival.

METHODS:

220 patients with CRLM planned for surgery will be enrolled in this study. Patients will be randomized to +/- RFA treatment before surgery. Under guidance of ultrasonography, a single-electrode RFA-needle is placed in a CRLM with a diameter of at least 3 cm, which is later going to be resected. In 20 of the patients, we will draw blood samples for determination of immune status both pre- and postoperatively. All patients will be part of a work-up with regular CT-scans.

ENDPOINTS:

Disease free survival and overall survival. Secondarily, we will examine the effect of RFA treatment of tumors on the innate and adaptive immune system in 20 patients

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jakob Kirkegård, MD, PhD; Phone Number: +4524995027; Email: jakob.kirkegaard@auh.rm.dk

Study Locations

• Denmark
  • Aarhus, Denmark, 8200
    • Recruiting
    • Aarhus University Hospital, Department of Surgery
    • Contact: Jakob Kirkegård, MD, PhD; Email: jakob.kirkegaard@auh.rm.dk
    • Principal Investigator: Frank V Mortensen, MD, DMSc
    • Sub-Investigator: Jakob Kirkegård, MD, PhD
    • Sub-Investigator: Andrea Lund, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with colorectal liver metastases planned for resection
• At least one tumor size >=3cm
• Performance status 0-1

Exclusion Criteria:

• Liver cirrhosis
• Extrahepatic metastases that can not be addressed curatively
• Other malignant diseases within 5 years prior to diagnosis
• Prior RFA treatment

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: Intervention (+RFA) arm; Preoperative partial RFA necrosis in the liver metastasis followed by liver resection	Device: RFA (radiofrequency ablation); Preoperative RFA-induced partial necrosis of the liver metastasis
No Intervention: Control (-RFA) arm; Liver resection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Median survival in each arm	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
One-year survival	One-year survival in each arm	1 year
Two-year survival	Two-year survival in each arm	2 years
Three-year survival	Three-year survival in each arm	3 years
Recurrence rate	Recurrence rate at 1, 2, and 3 years follow-up	1, 2, and 3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complications	Immediate postoperative complications (bleeding, surgical site infection, intraabdominal abscesses, bile leak)	30-day postoperatively

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Aarhus University Hospital; Rigshospitalet, Denmark
• Investigators: Principal Investigator: Frank V Mortensen, MD, DMSc, Aarhus University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 2022
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: March 9, 2021
• First Submitted That Met QC Criteria: March 12, 2021
• First Posted (Actual): March 15, 2021

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Liver Diseases; Neoplastic Processes; Neoplasm Metastasis; Liver Neoplasms
• Other Study ID Numbers: ISCOLIM

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