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

Primary Purpose

Immune Evasion, Tumor, Neoplastic Cells, Circulating, Circulating Tumor Cell

Status

Unknown status

Phase

Not Applicable

Locations

France

Study Type

Interventional

Intervention

RFA interventions

About this trial

This is an interventional other trial for Immune Evasion, Tumor focused on measuring Colo-rectal cancer, Lung metastasis, Radiofrequency ablation, Tumor infiltrating lymphocytes, Circulating tumor cells, Circulating DNA

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patient older than 18 years-old.
OMS performance status ≤ 2.
Colorectal cancer histologically established previously.
Primary tumor resected.
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.
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)
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.

Sites / Locations

Institut BergonieRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Single arm

Arm Description

Each patient is treated with 2 RFA interventions.

Outcomes

Primary Outcome Measures

Immune response triggered by RFA: Change from rate of tumor infiltrating T lymphocytes on tumoral stroma measured before and after RFA1.

Immune response triggered by RFA: Change from rate of tumor infiltrating T lymphocytes on tumoral stroma measured before and after RFA2.

Immune response triggered by RFA: Quantification of interaction of PD-1 and PD-L1 in lung metastases using immune Förster Resonance Energy Transfer (iFRET).

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.

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.

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.

Rate of Circulating DNA and tumor cells.

Expression of PDL-1 ligand on tumor cells from biopsies.

Change from baseline size of RFA treated tumor sites at 3 months based on CT scanner.

Change from baseline size of RFA treated tumor sites at 6 months based on CT scanner.

Change from baseline size of RFA treated tumor sites at 9 months based on CT scanner.

Change from baseline size of RFA treated tumor sites at 12 months based on CT scanner.

Change from baseline metastatic disease at 3 months

Change from baseline metastatic disease at 6 months

Change from baseline metastatic disease at 9 months

Change from baseline metastatic disease at 12 months

Full Information

NCT ID

NCT03960021

First Posted

April 2, 2019

Last Updated

May 21, 2019

Sponsor

Institut Bergonié

Collaborators

Groupement Interrégional de Recherche Clinique et d'Innovation

1. Study Identification

Unique Protocol Identification Number

NCT03960021

Brief Title

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

Acronym

ARFIM

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2019

Overall Recruitment Status

Unknown status

Study Start Date

March 4, 2019 (Actual)

Primary Completion Date

March 2021 (Anticipated)

Study Completion Date

March 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Institut Bergonié

Collaborators

Groupement Interrégional de Recherche Clinique et d'Innovation

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

Colo-rectal cancer, Lung metastasis, Radiofrequency ablation, Tumor infiltrating lymphocytes, Circulating tumor cells, Circulating DNA

7. Study Design

Primary Purpose

Other

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Single arm

Arm Type

Experimental

Arm Description

Each patient is treated with 2 RFA interventions.

Intervention Type

Radiation

Intervention Name(s)

RFA interventions

Intervention Description

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.

Primary Outcome Measure Information:

Title

Immune response triggered by RFA: Change from rate of tumor infiltrating T lymphocytes on tumoral stroma measured before and after RFA1.

Time Frame

Day 1

Title

Immune response triggered by RFA: Change from rate of tumor infiltrating T lymphocytes on tumoral stroma measured before and after RFA2.

Time Frame

Week 6

Title

Immune response triggered by RFA: Quantification of interaction of PD-1 and PD-L1 in lung metastases using immune Förster Resonance Energy Transfer (iFRET).

Time Frame

Day 1

Title

Immune response triggered by RFA: Quantification of interaction of PD-1 and PD-L1 in lung metastases using immune Förster Resonance Energy Transfer (iFRET).

Time Frame

Day 2

Title

Immune response triggered by RFA: Quantification of interaction of PD-1 and PD-L1 in lung metastases using immune Förster Resonance Energy Transfer (iFRET).

Time Frame

Week 6

Secondary Outcome Measure Information:

Title

Time Frame

Day 1

Title

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.

Time Frame

Day 1

Title

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.

Time Frame

Day 2

Title

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.

Time Frame

Week 6

Title

Rate of Circulating DNA and tumor cells.

Time Frame

Day 1

Title

Rate of Circulating DNA and tumor cells.

Time Frame

Day 2

Title

Rate of Circulating DNA and tumor cells.

Time Frame

Week 6

Title

Expression of PDL-1 ligand on tumor cells from biopsies.

Time Frame

Day 1

Title

Expression of PDL-1 ligand on tumor cells from biopsies.

Time Frame

Week 6

Title

Change from baseline size of RFA treated tumor sites at 3 months based on CT scanner.

Time Frame

Month 3

Title

Change from baseline size of RFA treated tumor sites at 6 months based on CT scanner.

Time Frame

Month 6

Title

Change from baseline size of RFA treated tumor sites at 9 months based on CT scanner.

Time Frame

Month 9

Title

Change from baseline size of RFA treated tumor sites at 12 months based on CT scanner.

Time Frame

Month 12

Title

Change from baseline metastatic disease at 3 months

Time Frame

Month 3

Title

Change from baseline metastatic disease at 6 months

Time Frame

Month 6

Title

Change from baseline metastatic disease at 9 months

Time Frame

Month 9

Title

Change from baseline metastatic disease at 12 months

Time Frame

Month 12

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Jean PALUSSIERE, MD

Phone

+33.5.56.33.33.33

j.palussiere@bordeaux.unicancer.fr

First Name & Middle Initial & Last Name or Official Title & Degree

Simone MATHOULIN-PELISSIER, MD, PhD

s.mathoulin@bordeaux.unicancer.fr

Facility Information:

Facility Name

Institut Bergonie

City

Bordeaux

ZIP/Postal Code

33076

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jean PALUSSIERE, MD

Phone

+33.5.56.33.33.33

j.palussiere@bordeaux.unicancer.fr

First Name & Middle Initial & Last Name & Degree

Marianne FONCK, MD

m.fonck@bordeaux.unicancer.fr

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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