Improving Survival of COlorectal LIver Metastases by RFA-mediated Immunostimulation

Study Overview
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Brief Summary
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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.

Detailed Description
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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

Official Title
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Improving Survival of COlorectal LIver Metastases by RFA-mediated Immunostimulation

Conditions
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Liver Metastasis Colon Cancer

Intervention / Treatment
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* Device: RFA (radiofrequency ablation)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention (+RFA) arm<br>Preoperative partial RFA necrosis in the liver metastasis followed by liver resection | Device: RFA (radiofrequency ablation)<br>* Preoperative RFA-induced partial necrosis of the liver metastasis<br>|
| No Intervention: Control (-RFA) arm<br>Liver resection | |

What is the study measuring?
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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 |