A Prospective Study of Monitoring Immune Response in Locally Advanced Cervix Cancer

Not Applicable

• Conditions: Cervical Cancer
• Interventions: Drug: Cisplatin

• Registration Number: NCT03559803
• Lead Sponsor: Sichuan University

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.

Study Timeline

• Study Start: 2016-10
• Study First Submitted: 2018-04-09
• Study First Submitted QC: 2018-06-14
• Study First Posted: 2018-06-18
• Status Verified: 2019-01
• Last Update Submitted: 2019-01-18
• Last Update Posted: 2019-01-22
• Primary Completion: 2019-12
• Study Completion: 2019-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 58

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.

5. Patients must be affiliated to a Social Security System. 6. Patient information and written informed consent form signed.

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cisplatin	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
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 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

Trial Locations

Locations (2)

Guizhou Province People's Hospital; 🇨🇳 Guizhou, Guizhou, China

West China Hospital, Sichuan University; 🇨🇳 Chendu, Sichuan, China