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

Sponsor

Institut Bergonié (Other)

Overall Status

Unknown status

CT.gov ID

NCT03960021

Collaborator

Groupement Interrégional de Recherche Clinique et d'Innovation (Other)

Enrollment

Location

Arm

35.9

Anticipated Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Immune Evasion, Tumor Neoplastic Cells, Circulating Circulating Tumor Cell Pulmonary Metastasis Colo-rectal Cancer	Radiation: RFA interventions	N/A

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

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

Actual Study Start Date :

Mar 4, 2019

Anticipated Primary Completion Date :

Mar 1, 2021

Anticipated Study Completion Date :

Mar 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single arm Each patient is treated with 2 RFA interventions.	Radiation: 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.

Arm

Intervention/Treatment

Experimental: Single arm

Each patient is treated with 2 RFA interventions.

Radiation: 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.

Outcome Measures

Primary Outcome Measures

Immune response triggered by RFA: Change from rate of tumor infiltrating T lymphocytes on tumoral stroma measured before and after RFA1. [Day 1]
Immune response triggered by RFA: Change from rate of tumor infiltrating T lymphocytes on tumoral stroma measured before and after RFA2. [Week 6]
Immune response triggered by RFA: Quantification of interaction of PD-1 and PD-L1 in lung metastases using immune Förster Resonance Energy Transfer (iFRET). [Day 1]
Immune response triggered by RFA: Quantification of interaction of PD-1 and PD-L1 in lung metastases using immune Förster Resonance Energy Transfer (iFRET). [Day 2]
Immune response triggered by RFA: Quantification of interaction of PD-1 and PD-L1 in lung metastases using immune Förster Resonance Energy Transfer (iFRET). [Week 6]

Secondary Outcome Measures

Immune response triggered by RFA: Distribution of blood factors related to the immune response of the kinetics of peripheral blood T lymphocytes subsets NK, CD4, CD8 and their activated receptor subgroups HLADR+, CD25+, CD38+ release before RFA1. [Day 1]
Immune response triggered by RFA: Change from baseline (before RFA1) blood factors related to the immune response of the kinetics of peripheral blood T lymphocytes subsets NK, CD4, CD8. [Day 1]
Immune response triggered by RFA: Change from baseline (before RFA1) blood factors related to the immune response of the kinetics of peripheral blood T lymphocytes subsets NK, CD4, CD8. [Day 2]
Immune response triggered by RFA: Change from baseline (before RFA2) blood factors related to the immune response of the kinetics of peripheral blood T lymphocytes subsets NK, CD4, CD8. [Week 6]
Rate of Circulating DNA and tumor cells. [Day 1]
Rate of Circulating DNA and tumor cells. [Day 2]
Rate of Circulating DNA and tumor cells. [Week 6]
Expression of PDL-1 ligand on tumor cells from biopsies. [Day 1]
Expression of PDL-1 ligand on tumor cells from biopsies. [Week 6]
Change from baseline size of RFA treated tumor sites at 3 months based on CT scanner. [Month 3]
Change from baseline size of RFA treated tumor sites at 6 months based on CT scanner. [Month 6]
Change from baseline size of RFA treated tumor sites at 9 months based on CT scanner. [Month 9]
Change from baseline size of RFA treated tumor sites at 12 months based on CT scanner. [Month 12]
Change from baseline metastatic disease at 3 months [Month 3]
Change from baseline metastatic disease at 6 months [Month 6]
Change from baseline metastatic disease at 9 months [Month 9]
Change from baseline metastatic disease at 12 months [Month 12]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patient older than 18 years-old.
OMS performance status ≤ 2.
Colorectal cancer histologically established previously.
Primary tumor resected.
Lung metastasis:
Bilateral metastasis (or unilateral metastases that need to undergo the RF in two separate sessions due to the number of metastases ≥ 5)
Maximal diameter ≤ 4 cm,
non or slowly progressive, with or without chemotherapy,
eligible to RFA.
Thorax-abdomen-pelvis CT scan and PET scan:
performed within 8 weeks before inclusion
finding no more than 10 metastatic nodules (liver + lung or lung alone)
Maximum of 8 weeks between the last cycle of chemotherapy and the first RFA.
Decision of local treatment agreed at the multidisciplinary digestive tumor board.
Life expectancy ≥ 3 months.
Voluntarily signed and dated written informed consent prior to any study specific procedure.
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:

Other than lung or liver metastases.
Contraindication to general anesthesia.
Contraindication to RFA: tumor location (< 1cm from the hilum), lung insufficiency (FEV/sec < 1l),
Pregnant or lactating women.
Concomitant participation to another interventional research.
Patient unable to follow and comply with the study procedures because of any geographical, social or psychological reasons.
Patient deprived of liberty or under legal protection measure.