Cervical Cancer
Conditions
Keywords
Cervical Cancer, PD-L1, Concurrent Chemoradiotherapy
Brief summary
Perspectives: To analyse if the change of specific immune response will correlate with clinical effect of advanced cervix cancer after radio-chemotherapy. To evaluate the specific immune response throughout monitor the change of the programmed death-1(PD-1) in CD8 T cell and CD4 T cell and Treg cell in blood at baseline, before first brachytherapy and before the last brachytherapy in the advanced Cervix Cancer patients. To use immunohistochemistry (IHC) technique to monitor the change of programmed death-ligand 1 (PD-L1),CD68,CD8,CD4,PD1 and Treg expression in biopsy at baseline, before first brachytherapy and before the last brachytherapy in the advanced Cervix Cancer patients. To detect the change of T cell receptor(TCR) repertoire and Tumor mutation burden (TMB) at baseline, before first brachytherapy and before the last brachytherapy in the advanced Cervix Cancer patients.
Detailed description
Cervical cancer is the fourth most common cancer among women worldwide. At present, patients with cervical cancer are treated with radical hysterectomy and pelvic lymphadenectomy or chemoradiation. To improve the prognosis of cervical cancer patients, novel immunotherapeutic strategies need to be developed. Now there are some clinical phase I/II trials ongoing to assess the effects of ipilimumab, pembrolizumab and nivolumab in advanced cervical cancer,but information on the clinical significance of PD-L1 expression in cervical cancer is largely lacking.In this study, the investigator's primary objective: To analyse if the change of specific immune response will correlate with clinical effect of advanced cervix cancer after radio-chemotherapy. To evaluate the specific immune response throughout monitor the change of PD-1 in CD8 T cell and CD4 T cell and Treg cell in blood at baseline, before first brachytherapy and before the last brachytherapy in the advanced Cervix Cancer patients. To use IHC technique to monitor the change of PD-L1, CD68,CD8,CD4,PD1 and Treg expression in biopsy at baseline, before first brachytherapy and before the last brachytherapy in the advanced Cervix Cancer patients. To detect the change of TCR repertoire and TMB at baseline, before first brachytherapy and before the last brachytherapy in the advanced Cervix Cancer patients.
Interventions
DRUGCisplatin
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).
Sponsors
Sichuan University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Age:18-70 years. 2. All FIGO stages cervical cancers which are the matter for radiochemotherapy and exclusive brachytherapy indications. 3. ECOG:0-1. 4. Ability to give informed consent. 4\. Patients must be affiliated to a Social Security System. 6. Patient information and written informed consent form signed.
Exclusion criteria
1. Known autoimmune disorder. 2. History of HIV and/ or active hepatitis infection. 3. History of pelvic radiation or radio-chemotherapy. 4. Recurrent or metastatic cervical cancer. 5. Contra-indication for cisplatin. 6. Patient pregnant and/or breastfeeding. 7. Patients with psychological or familial disease potentially hampering compliance with the study protocol and follow-up schedule
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The change of expression of PD-L1+ on cervix biopsies | From baseline,3 weeks,2 months | The biopsy was collected at baseline,3 weeks,2 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The change of expression of PD1 on the non-regulatory CD4+ and CD8+ lymphocytes and Treg cells | baseline,3 weeks,2 months | The blood was collected at baseline,3 weeks,2 months |
| The diversity of T-cell Repertoire in cervix biopsies and blood, respectively | baseline,3 weeks,2 months | The blood and biopsies were collected at baseline,3 weeks,2 months |
| The change of expression of CD8+PD1+ lymphocytes infiltrate on cervix biopsies | baseline,3 weeks,2 months | The biopsy was collected at baseline,3 weeks,2 months |
Countries
China
Outcome results
None listed