Clinical trial NCT04798898: Improving Survival of COlorectal LIver Metastases by RFA-mediated Immunostimulation
Official title: Improving Survival of COlorectal LIver Metastases by RFA-mediated Immunostimulation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Liver Metastasis Colon Cancer
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Aarhus University Hospital
name: Rigshospitalet, Denmark
First posted: 2021-03-15
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Eligibility criteria: 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

Primary outcomes:
measure: Overall survival
timeFrame: 3 years
Secondary outcomes:
measure: One-year survival
timeFrame: 1 year
measure: Two-year survival
timeFrame: 2 years
measure: Three-year survival
timeFrame: 3 years
measure: Recurrence rate
timeFrame: 1, 2, and 3 years
Other outcomes:
measure: Complications
timeFrame: 30-day postoperatively
Locations:
city: Aarhus
country: Denmark
facility: Aarhus University Hospital, Department of Surgery
Study officials:
affiliation: Aarhus University Hospital
name: Frank V Mortensen, MD, DMSc
role: PRINCIPAL_INVESTIGATOR
References: