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

Sponsor

University of Aarhus (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04798898

Collaborator

Aarhus University Hospital (Other), Rigshospitalet, Denmark (Other)

200

Enrollment

Location

Arms

Anticipated Duration (Months)

7.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Liver Metastasis Colon Cancer	Device: RFA (radiofrequency ablation)	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Improving Survival of COlorectal LIver Metastases by RFA-mediated Immunostimulation

Anticipated Study Start Date :

Sep 1, 2022

Anticipated Primary Completion Date :

Jun 1, 2023

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Overall survival [3 years]
Median survival in each arm

Secondary Outcome Measures

One-year survival [1 year]
One-year survival in each arm
Two-year survival [2 years]
Two-year survival in each arm
Three-year survival [3 years]
Three-year survival in each arm
Recurrence rate [1, 2, and 3 years]
Recurrence rate at 1, 2, and 3 years follow-up

Other Outcome Measures

Complications [30-day postoperatively]
Immediate postoperative complications (bleeding, surgical site infection, intraabdominal abscesses, bile leak)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Aarhus University Hospital, Department of Surgery	Aarhus		Denmark	8200

Sponsors and Collaborators

University of Aarhus
Aarhus University Hospital
Rigshospitalet, Denmark

Investigators

Principal Investigator: Frank V Mortensen, MD, DMSc, Aarhus University Hospital

Study Documents (Full-Text)

Study Protocol and Statistical Analysis Plan - Nov 1, 2021

More Information

Publications

None provided.

Responsible Party:

University of Aarhus

ClinicalTrials.gov Identifier:

NCT04798898

Other Study ID Numbers:

ISCOLIM

First Posted:

Mar 15, 2021

Last Update Posted:

May 19, 2022

Last Verified:

May 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Neoplasm Metastasis

Liver Neoplasms

Study Results

No Results Posted as of May 19, 2022