Immune Mechanisms After Radiofrequency Ablation of Pulmonary Metastases From Colorectal Cancer Origin

NCT ID: NCT03960021

Last Updated: 2025-10-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-04
• Study Completion Date: 2022-03-15

Brief Summary

Local percutaneous thermal ablation is frequently proposed in the management of metastatic diseases. Radiofrequency ablation (RFA) has demonstrated good results when the metastatic disease is limited and slowly evolving. The destruction of solid metastasis by RF leads to inflammatory and immunological mechanisms that remain poorly understood. These pathological events may influence the overall and anti-tumor host immune responses. The purpose of the study is to identify and quantify some immune mechanisms triggered by RFA of pulmonary metastases from colorectal cancer origin.

Detailed Description

RFA could provide activatory signals and become a source of tumor antigens for the immune system. Generating a massive and transient release of antigens, RFA could boost lymphocyte proliferation and production of inflammatory cytokines in response to tumor extracts. Herein, the investigator aims to demonstrate that RFA can amplify the specific T cell response in metastatic cancer patients. In order to ensure this, he plans to assess and quantify tumor infiltrating lymphocytes through tumoral biopsies. He also plans to measure the CD4, CD8 and NK lymphocytes release, the circulating DNA and tumoral cells release, during RFA of lung metastases. On tumoral biopsies, the expression of PDL-1 ligand will also be evaluated and measured. Participants with bilateral metastases or with 5 or more unilateral metastases will be recruited. The two RFA interventions will be carried out within 4-6 weeks of each other. Blood samples and tumoral biopsies will be performed during each intervention. Biopsies will be performed on a metastasis before the thermal ablation. Blood samples will be performed just before RFA, 30 min after RFA and one day after. Analysis, identification and measure of lymphocytes release will be performed with flow cytometry. All analysis and measurements will be performed in the Bio-Pathology department of Institut Bergonié.

Conditions

Immune Evasion, Tumor; Neoplastic Cells, Circulating; Circulating Tumor Cell; Pulmonary Metastasis; Colo-rectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single arm

Each patient is treated with 2 RFA interventions.

Group Type: EXPERIMENTAL

RFA interventions

Intervention Type: RADIATION

Each patient is treated with 2 RFA interventions. Abiopsy of one metastasis is done at each RF session. Histological samples are sent to the Bio-pathology department of Institut Bergonié for tumor infiltrating lymphocytes counting. Primary outcome results from this counting (stromal TILs ≥ 20% is considered as a significant level, a comparative measurement before and after RF will be performed). In parallel blood samples are performed before and after RFA to analyze the kinetics of peripheral blood T lymphocytes subsets, tumoral circulating cells and tumoral DNA.

Interventions

RFA interventions

Each patient is treated with 2 RFA interventions. Abiopsy of one metastasis is done at each RF session. Histological samples are sent to the Bio-pathology department of Institut Bergonié for tumor infiltrating lymphocytes counting. Primary outcome results from this counting (stromal TILs ≥ 20% is considered as a significant level, a comparative measurement before and after RF will be performed). In parallel blood samples are performed before and after RFA to analyze the kinetics of peripheral blood T lymphocytes subsets, tumoral circulating cells and tumoral DNA.

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

1. Patient older than 18 years-old.

2. OMS performance status ≤ 2.

3. Colorectal cancer histologically established previously.

4. Primary tumor resected.

5. Lung metastasis:

1. Bilateral metastasis (or unilateral metastases that need to undergo the RF in two separate sessions due to the number of metastases ≥ 5)

2. Maximal diameter ≤ 4 cm,

3. non or slowly progressive, with or without chemotherapy,

4. eligible to RFA.

6. Thorax-abdomen-pelvis CT scan and PET scan:

1. performed within 8 weeks before inclusion

2. finding no more than 10 metastatic nodules (liver + lung or lung alone)

7. Maximum of 8 weeks between the last cycle of chemotherapy and the first RFA.

8. Decision of local treatment agreed at the multidisciplinary digestive tumor board.

9. Life expectancy ≥ 3 months.

10. Voluntarily signed and dated written informed consent prior to any study specific procedure.

11. Patients with a French social security in compliance with the Law relating to biomedical research (Article 1121-11 of French Public Health Code).

Exclusion Criteria

1. Other than lung or liver metastases.

2. Contraindication to general anesthesia.

3. Contraindication to RFA: tumor location (< 1cm from the hilum), lung insufficiency (FEV/sec < 1l),

4. Pregnant or lactating women.

5. Concomitant participation to another interventional research.

6. Patient unable to follow and comply with the study procedures because of any geographical, social or psychological reasons.

7. Patient deprived of liberty or under legal protection measure.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Groupement Interrégional de Recherche Clinique et d'Innovation

OTHER

Sponsor Role: collaborator

Institut Bergonié

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jean PALUSSIERE, MD

Role: PRINCIPAL_INVESTIGATOR

Institut Bergonié

Locations

Institut Bergonie

Bordeaux, , France

Countries

France

References

Miles J, Soubeyran I, Marliot F, Pangon N, Italiano A, Bellera C, Ward SG, Pages F, Palussiere J, Larijani B. Determination of Interactive States of Immune Checkpoint Regulators in Lung Metastases after Radiofrequency Ablation. Cancers (Basel). 2022 Nov 22;14(23):5738. doi: 10.3390/cancers14235738.

Reference Type: BACKGROUND

PMID: 36497220 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2018-A01996-49

Identifier Type: OTHER

Identifier Source: secondary_id

IB 2018-03

Identifier Type: -

Identifier Source: org_study_id