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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03255252
Recruitment Status : Active, not recruiting
First Posted : August 21, 2017
Last Update Posted : December 21, 2021
Sponsor:
Information provided by (Responsible Party):
Institut du Cancer de Montpellier - Val d'Aurelle

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Cervical Cancer Drug: Cisplatin injection Combination Product: radiotherapy Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 29 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: radiothérapy with concomittant chemotherapy
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Assessment Study to Evaluate Specific Immune Response in Locally Advanced Cervix Cancer After Radio-chemotherapy (IMMUVIX)
Actual Study Start Date : July 15, 2017
Estimated Primary Completion Date : July 2022
Estimated Study Completion Date : July 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Biopsy
Drug Information available for: Cisplatin

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).




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

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): NCT03255252


Locations
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France
Clinique Beausoleil
Montpellier, France, 34070
CHRU Montpellier
Montpellier, France, 34295
ICM Val d'Aurelle
Montpellier, France, 34298
Sponsors and Collaborators
Institut du Cancer de Montpellier - Val d'Aurelle
Investigators
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Study Chair: Jean-Pierre BLEUSE, MD ICM Val d'Aurelle
Publications:

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Responsible Party: Institut du Cancer de Montpellier - Val d'Aurelle
ClinicalTrials.gov Identifier: NCT03255252    
Other Study ID Numbers: ICM-URC 2015/27
First Posted: August 21, 2017    Key Record Dates
Last Update Posted: December 21, 2021
Last Verified: December 2021
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
Additional relevant MeSH terms:
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Uterine Cervical Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Cisplatin
Antineoplastic Agents