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

Phase 2

Terminated

• Conditions: Cervical Cancer
• Interventions: Drug: Cisplatin injection; Combination Product: radiotherapy

• Registration Number: NCT03255252
• Lead Sponsor: 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.

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 Timeline

• Study Start: 2017-07-15
• Study First Submitted: 2017-08-10
• Study First Submitted QC: 2017-08-18
• Study First Posted: 2017-08-21
• Primary Completion: 2022-06-16
• Study Completion: 2023-11-23
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-16
• Last Update Posted: 2025-05-18

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Female
• Target Recruitment: 29

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cisplatin	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.
Cisplatin	radiotherapy	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.

Primary Outcome Measures

Name	Time	Method
Expression of CD8+CD39+PD1+ lymphocytes infiltrate on cervix biopsies	through study completion, an average of 1 year disease free survival	Cervix biopsies analysis

Secondary Outcome Measures

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

Trial Locations

Locations (3)

Clinique Beausoleil; 🇫🇷 Montpellier, France

CHRU Montpellier; 🇫🇷 Montpellier, France

Moussin Aurore; 🇫🇷 Montpellier, France