Clinical trial NCT03559803: A Prospective Study of Monitoring Immune Response in Locally Advanced Cervix Cancer
Official title: A Prospective Study of Dynamic Monitoring Specific Immune Response in Locally Advanced Cervix Cancer After Radio-chemotherapy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Cervical Cancer
Keywords: Cervical Cancer
PD-L1
Concurrent Chemoradiotherapy
Lead sponsor: Sichuan University
Sponsor class: OTHER
First posted: 2018-06-18
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: The change of expression of PD-L1+ on cervix biopsies
timeFrame: From baseline,3 weeks,2 months
Secondary outcomes:
measure: The change of expression of PD1 on the non-regulatory CD4+ and CD8+ lymphocytes and Treg cells
timeFrame: baseline,3 weeks,2 months
measure: The diversity of T-cell Repertoire in cervix biopsies and blood, respectively
timeFrame: baseline,3 weeks,2 months
measure: The change of expression of CD8+PD1+ lymphocytes infiltrate on cervix biopsies
timeFrame: baseline,3 weeks,2 months
Other outcomes:
Locations:
city: Guizhou
country: China
facility: Guizhou Province People's Hospital
state: Guizhou
city: Chendu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
Study officials:
affiliation: West China Hospital
name: You Lu, MD
role: PRINCIPAL_INVESTIGATOR
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