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出境医 / 临床实验 / Immune Mechanisms After Radiofrequency Ablation of Pulmonary Metastases From Colorectal Cancer Origin (ARFIM)

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

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 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.
Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated 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 : March 4, 2019
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : March 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.
Outcome Measures
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 ]

Eligibility Criteria
Layout table for eligibility information
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.
Contacts and Locations

Contacts
Layout table for location contacts
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
Layout table for location information
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
Tracking Information
First Submitted Date  ICMJE April 2, 2019
First Posted Date  ICMJE May 22, 2019
Last Update Posted Date May 22, 2019
Actual Study Start Date  ICMJE March 4, 2019
Estimated Primary Completion Date March 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 21, 2019)
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: May 21, 2019)
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • Rate of Circulating DNA and tumor cells. [ Time Frame: Day 1 ]
  • Rate of Circulating DNA and tumor cells. [ Time Frame: Day 2 ]
  • Rate of Circulating DNA and tumor cells. [ Time Frame: Week 6 ]
  • Expression of PDL-1 ligand on tumor cells from biopsies. [ Time Frame: Day 1 ]
  • Expression of PDL-1 ligand on tumor cells from biopsies. [ Time Frame: Week 6 ]
  • Change from baseline size of RFA treated tumor sites at 3 months based on CT scanner. [ Time Frame: Month 3 ]
  • Change from baseline size of RFA treated tumor sites at 6 months based on CT scanner. [ Time Frame: Month 6 ]
  • Change from baseline size of RFA treated tumor sites at 9 months based on CT scanner. [ Time Frame: Month 9 ]
  • Change from baseline size of RFA treated tumor sites at 12 months based on CT scanner. [ Time Frame: Month 12 ]
  • Change from baseline metastatic disease at 3 months [ Time Frame: Month 3 ]
  • Change from baseline metastatic disease at 6 months [ Time Frame: Month 6 ]
  • Change from baseline metastatic disease at 9 months [ Time Frame: Month 9 ]
  • Change from baseline metastatic disease at 12 months [ Time Frame: Month 12 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Immune Mechanisms After Radiofrequency Ablation of Pulmonary Metastases From Colorectal Cancer Origin
Official Title  ICMJE Immune Mechanisms After Radiofrequency Ablation of Pulmonary Metastases From Colorectal Cancer Origin- ARFIM Study
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE
  • Immune Evasion, Tumor
  • Neoplastic Cells, Circulating
  • Circulating Tumor Cell
  • Pulmonary Metastasis
  • Colo-rectal Cancer
Intervention  ICMJE 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.
Study Arms  ICMJE Experimental: Single arm
Each patient is treated with 2 RFA interventions.
Intervention: Radiation: RFA interventions
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 21, 2019) 		20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2022
Estimated Primary Completion Date March 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
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
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03960021
Other Study ID Numbers  ICMJE IB 2018-03
2018-A01996-49 ( Other Identifier: ID-RCB ANSM )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Institut Bergonié
Study Sponsor  ICMJE Institut Bergonié
Collaborators  ICMJE Groupement Interrégional de Recherche Clinique et d'Innovation
Investigators  ICMJE Not Provided
PRS Account Institut Bergonié
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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