CClinicalTrials.gg
TerminatedNCT03255252IMMUVIXUpdated May 18, 2025

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

A Phase 2 interventional study of Cisplatin injection and radiotherapy in Cervical Cancer, sponsored by Institut du Cancer de Montpellier - Val d'Aurelle. Terminated at 3 sites in France. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-05-18.

Sponsored by Institut du Cancer de Montpellier - Val d'Aurelle · Phase 2, Interventional, and Treatment

Why this study was terminated
insufficient recruitment
Phase
Phase 2
Study type
Interventional
Enrollment
29
Allocation
Not applicable
Ages
18 Years and older
Sex
Female
01

Study 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.
Read the 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.
02

Conditions studied

  • Cervical Cancer
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
Female
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
29 participants (actual)

Study arms

  • 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 · Combination Product: radiotherapy

Interventions

  • DrugCisplatin 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 productradiotherapy

    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).

05

What researchers measure

Primary outcomes

  1. Expression of CD8+CD39+PD1+ lymphocytes infiltrate on cervix biopsies

    Cervix biopsies analysis

    Time frame: through study completion, an average of 1 year disease free survival

Secondary outcomes

  1. Effect on 1-year DFS of other putative biomarkers (CD73, CD39, PD1 and Tim3) on the non-regulatory CD4+ and CD8+ lymphocytes

    Cervix biopsies and blood samples analysis

    Time frame: through study completion, an average of 1 year disease free survival

06

Study locations

3 sites
  • Clinique Beausoleil
    Montpellier, 34070, France
  • CHRU Montpellier
    Montpellier, 34295, France
  • Moussin Aurore
    Montpellier, 34298, France
07

References and documents

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Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT03255252
Lead sponsor
Institut du Cancer de Montpellier - Val d'Aurelle
Responsible party
Sponsor
First posted
Aug 21, 2017
Start date
Jul 15, 2017
Primary completion
Jun 16, 2022
Completion
Nov 23, 2023
Last update
May 18, 2025

Study contacts

Riou Olivier, MD
study chair · ICM Val d'Aurelle

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
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