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Assessment Study to Evaluate Specific Immune Response in Locally Advanced Cervix Cancer After Radio-chemotherapy

NCT03255252

Description:

Perspectives: - To set-up another clinical trial with this specific phenotype as the main stratification factor. Therefore a more aggressive or a more specific systemic treatment (with or without an immunomodulator) could be proposed to those selected patients in the field of personalized medicine. - To evaluate the use of the smear as a surrogate non-invasive technique to biopsy for immunomonitoring. - To use the CTC/PD-L1 assay as a liquid biopsy in future clinical trials for stratification and monitoring of cancer patients undergoing immune checkpoint treatments. This specific subset of CTCs might represent metastatic cells with a high potential to escape T cell-mediated lysis and might therefore be the actual targets of immunotherapy.

Related Conditions:
  • Cervical Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Assessment Study to Evaluate Specific Immune Response in Locally Advanced Cervix Cancer After Radio-chemotherapy
  • Official Title: Assessment Study to Evaluate Specific Immune Response in Locally Advanced Cervix Cancer After Radio-chemotherapy (IMMUVIX)

Clinical Trial IDs

  • ORG STUDY ID: ICM-URC 2015/27
  • NCT ID: NCT03255252

Conditions

  • Cervical Cancer

Interventions

DrugSynonymsArms
Cisplatin injectionCisplatin

Purpose

Perspectives: - To set-up another clinical trial with this specific phenotype as the main stratification factor. Therefore a more aggressive or a more specific systemic treatment (with or without an immunomodulator) could be proposed to those selected patients in the field of personalized medicine. - To evaluate the use of the smear as a surrogate non-invasive technique to biopsy for immunomonitoring. - To use the CTC/PD-L1 assay as a liquid biopsy in future clinical trials for stratification and monitoring of cancer patients undergoing immune checkpoint treatments. This specific subset of CTCs might represent metastatic cells with a high potential to escape T cell-mediated lysis and might therefore be the actual targets of immunotherapy.

Detailed Description

      Cervical cancer is a real worldwide health care issue. High-risk human papillomavirus
      (HR-HPV) chronic infection is a co-factor in the development of the cervical cancer.

      The HR-HPV genome encodes two oncoproteins (E6 and E7) which are required to sustain the
      malignant phenotype of pre-neoplastic lesions and are considered as foreign antigens
      recognized by the immune system, Many studies have suggested that local immunologic escape
      can cause the emergence of HPV-induced cervical cancer Radio-chemotherapy is the gold
      standard treatment for locally advanced cervical cancer, resulting in 2 year-control rates of
      about 70 to 85 %. A better and earlier understanding of the reasons for tumor escape may
      hopefully help to improve these outcomes.

      Both radiation and chemotherapy are myelosuppressive treatments, but new treatment modalities
      such as Intensity-Modulated Radiation Therapy (IMRT) may allow a more rapid hematologic
      recovery. In addition to this immunosuppressive microenvironment, a significant number of
      tumor-infiltrating lymphocytes (TILs) are detected in cervical cancer tissue, highlighting
      interactions between tumor and immune cells.

      Another issue is the fact that cancer cells develop different strategies to bypass the immune
      surveillance, such as a down-regulation of class I human leucocyte antigen (HLA) on tumor
      cells surface.

      Furthermore, there is growing evidence of the importance of immune cells in response to
      cervical cancer treatment. TILs have been correlated with cervical cancer patients' outcome.
      More precisely, the location and type of these immune cells seem to be of great importance
      for the tumor response to treatment.

      Receptors with negative regulatory function have been identified on the surface of those T
      cells, including CTLA4 and PD1 and seem to play a great role in tumor escape to treatment.

      The presence of circulating tumor cells (CTCs) was shown to be correlated with a poor
      patient's prognosis in many cancers. A recent study suggested a potential mechanism of immune
      escape of these CTCs resulting in metastasis spreading.

      The hypothesis of this study is that the frequency of PD1+,CD39+, specific phenotype of the
      non-regulatory CD4+ and CD8+ T cells among TILs is involved with the lack of response to the
      treatment and correlates with an early relapse after the treatment (i.e. patients with a very
      poor prognosis).

      Perspectives:

        -  To set-up another clinical trial with this specific phenotype as the main stratification
           factor. Therefore a more aggressive or a more specific systemic treatment (with or
           without an immunomodulator) could be proposed to those selected patients in the field of
           personalized medicine.

        -  To evaluate the use of the smear as a surrogate non-invasive technique to biopsy for
           immunomonitoring.

        -  To use the CTC/PD-L1 assay as a liquid biopsy in future clinical trials for
           stratification and monitoring of cancer patients undergoing immune checkpoint
           treatments. This specific subset of CTCs might represent metastatic cells with a high
           potential to escape T cell-mediated lysis and might therefore be the actual targets of
           immunotherapy.
    

Trial Arms

NameTypeDescriptionInterventions
CisplatinExperimentalWeekly cisplatin (40 mg/m²) will be administered during radiotherapy. At least 3 cycles of cisplatin should be performed according to the hematological and renal functions but not mandatory.
  • Cisplatin injection

Eligibility Criteria

        Inclusion Criteria:

          -  Age ≥ 18 years.

          -  HPV-positive cervical cancer proven* by biopsy.

          -  All FIGO stages cervical cancers which are the matter for radio-chemotherapy and
             exclusive brachytherapy indications.

          -  ECOG performance status ≤2.

          -  Ability to give informed consent.

          -  Patients must be affiliated to a Social Security System.

          -  Patient information and written informed consent form signed.

        Exclusion Criteria:

          -  Adenocarcinoma of cervix.

          -  Known autoimmune disorder.

          -  History of HIV and/ or hepatitis infection.

          -  History of pelvic radiation or radio-chemotherapy.

          -  Recurrent or metastatic cervical cancer.

          -  Contra-indication for cisplatin.

          -  Patient pregnant and/or breastfeeding.

          -  History of other malignancy within the previous 5 years (except for appropriately
             treated melanoma skin carcinoma).

          -  Patients with psychological, familial, sociological or geographical condition
             potentially hampering compliance with the study protocol and follow-up schedule
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Expression of CD8+CD39+PD1+ lymphocytes infiltrate on cervix biopsies
Time Frame:through study completion, an average of 1 year disease free survival
Safety Issue:
Description:Cervix biopsies analysis

Secondary Outcome Measures

Measure:Effect on 1-year DFS of other putative biomarkers (CD73, CD39, PD1 and Tim3) on the non-regulatory CD4+ and CD8+ lymphocytes
Time Frame:through study completion, an average of 1 year disease free survival
Safety Issue:
Description:Cervix biopsies and blood samples analysis

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Institut du Cancer de Montpellier - Val d'Aurelle

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