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

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ClinicalTrials.gov Identifier: NCT03960021
Recruitment Status : Recruiting
First Posted : May 22, 2019
Last Update Posted : May 22, 2019
Sponsor:
Collaborator:
Groupement Interrégional de Recherche Clinique et d'Innovation
Information provided by (Responsible Party):
Institut Bergonié

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 Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
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 : March 4, 2019
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : March 2022

Resource links provided by the National Library of Medicine


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.




Primary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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 Measures :
  1. 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. [ Time Frame: Day 1 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. Rate of Circulating DNA and tumor cells. [ Time Frame: Day 1 ]
  6. Rate of Circulating DNA and tumor cells. [ Time Frame: Day 2 ]
  7. Rate of Circulating DNA and tumor cells. [ Time Frame: Week 6 ]
  8. Expression of PDL-1 ligand on tumor cells from biopsies. [ Time Frame: Day 1 ]
  9. Expression of PDL-1 ligand on tumor cells from biopsies. [ Time Frame: Week 6 ]
  10. Change from baseline size of RFA treated tumor sites at 3 months based on CT scanner. [ Time Frame: Month 3 ]
  11. Change from baseline size of RFA treated tumor sites at 6 months based on CT scanner. [ Time Frame: Month 6 ]
  12. Change from baseline size of RFA treated tumor sites at 9 months based on CT scanner. [ Time Frame: Month 9 ]
  13. Change from baseline size of RFA treated tumor sites at 12 months based on CT scanner. [ Time Frame: Month 12 ]
  14. Change from baseline metastatic disease at 3 months [ Time Frame: Month 3 ]
  15. Change from baseline metastatic disease at 6 months [ Time Frame: Month 6 ]
  16. Change from baseline metastatic disease at 9 months [ Time Frame: Month 9 ]
  17. Change from baseline metastatic disease at 12 months [ Time Frame: Month 12 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03960021


Contacts
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Contact: Jean PALUSSIERE, MD +33.5.56.33.33.33 j.palussiere@bordeaux.unicancer.fr
Contact: Simone MATHOULIN-PELISSIER, MD, PhD s.mathoulin@bordeaux.unicancer.fr

Locations
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France
Institut Bergonie Recruiting
Bordeaux, France, 33076
Contact: Jean PALUSSIERE, MD    +33.5.56.33.33.33    j.palussiere@bordeaux.unicancer.fr   
Contact: Marianne FONCK, MD       m.fonck@bordeaux.unicancer.fr   
Sponsors and Collaborators
Institut Bergonié
Groupement Interrégional de Recherche Clinique et d'Innovation

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Responsible Party: Institut Bergonié
ClinicalTrials.gov Identifier: NCT03960021     History of Changes
Other Study ID Numbers: IB 2018-03
2018-A01996-49 ( Other Identifier: ID-RCB ANSM )
First Posted: May 22, 2019    Key Record Dates
Last Update Posted: May 22, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Institut Bergonié:
Colo-rectal cancer
Lung metastasis
Radiofrequency ablation
Tumor infiltrating lymphocytes
Circulating tumor cells
Circulating DNA

Additional relevant MeSH terms:
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Neoplasms
Colorectal Neoplasms
Neoplasm Metastasis
Neoplasms, Second Primary
Rectal Neoplasms
Neoplastic Cells, Circulating
Lung Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplastic Processes
Pathologic Processes
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases