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

June 6, 2023 updated by: Institut du Cancer de Montpellier - Val d'Aurelle

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

29

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Montpellier, France, 34070
        • Clinique BEAUSOLEIL
      • Montpellier, France, 34295
        • CHRU Montpellier
      • Montpellier, France, 34298
        • Moussin Aurore

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cisplatin
Weekly 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.
Drug: Cisplatin injection
Weekly 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.
Combination product: radiotherapy
A total dose of 45Gy in 25 fractions to the PTV is considered standard but simultaneous integrated boost or two steps boost to specific volumes (positive lymph nodes for example) are accepted and left to the investigator's discretion).

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Cervix biopsies and blood samples analysis
through study completion, an average of 1 year disease free survival

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institut du Cancer de Montpellier - Val d'Aurelle

Investigators

  • Study Chair: Riou Olivier, MD, ICM Val D'Aurelle

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 15, 2017

Primary Completion (Actual)

June 16, 2022

Study Completion (Estimated)

July 1, 2024

Study Registration Dates

First Submitted

August 10, 2017

First Submitted That Met QC Criteria

August 18, 2017

First Posted (Actual)

August 21, 2017

Study Record Updates

Last Update Posted (Actual)

June 7, 2023

Last Update Submitted That Met QC Criteria

June 6, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ICM-URC 2015/27

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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