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

NCT03559803 | Unknown

• 1 other identifier: GHR-002
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 2

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.

Conditions

Cervical Cancer

Keywords

Cervical Cancer; PD-L1; Concurrent Chemoradiotherapy

Outcome Measures

Primary Outcomes (1)

• The change of expression of PD-L1+ on cervix biopsies

  The biopsy was collected at baseline,3 weeks,2 months

  From baseline,3 weeks,2 months

Secondary Outcomes (3)

• The change of expression of PD1 on the non-regulatory CD4+ and CD8+ lymphocytes and Treg cells

  baseline,3 weeks,2 months

• The diversity of T-cell Repertoire in cervix biopsies and blood, respectively

  baseline,3 weeks,2 months

• The change of expression of CD8+PD1+ lymphocytes infiltrate on cervix biopsies

  baseline,3 weeks,2 months

Study Arms (1)

Cisplatin

EXPERIMENTAL

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

Interventions

Cisplatin DRUG

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).

Also known as: radiotherapy

Cisplatin

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age:18-70 years.
• All FIGO stages cervical cancers which are the matter for radiochemotherapy and exclusive brachytherapy indications.
• ECOG:0-1.
• Ability to give informed consent.
• \. Patients must be affiliated to a Social Security System. 6. Patient information and written informed consent form signed.

You may not qualify if:

• Known autoimmune disorder.
• History of HIV and/ or active hepatitis infection.
• History of pelvic radiation or radio-chemotherapy.
• Recurrent or metastatic cervical cancer.
• Contra-indication for cisplatin.
• Patient pregnant and/or breastfeeding.
• Patients with psychological or familial disease potentially hampering compliance with the study protocol and follow-up schedule

Sponsors & Collaborators

• Sichuan University: lead

Study Sites (2)

Guizhou Province People's Hospital

Guizhou, Guizhou, China

Location

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

Location

Related Publications (10)

• Jayshree RS, Sreenivas A, Tessy M, Krishna S. Cell intrinsic & extrinsic factors in cervical carcinogenesis. Indian J Med Res. 2009 Sep;130(3):286-95.

  PMID: 19901438 BACKGROUND

• Folkl A, Bienzle D. Structure and function of programmed death (PD) molecules. Vet Immunol Immunopathol. 2010 Mar 15;134(1-2):33-8. doi: 10.1016/j.vetimm.2009.10.006. Epub 2009 Oct 14.

  PMID: 19931186 BACKGROUND

• Gao Q, Wang XY, Qiu SJ, Yamato I, Sho M, Nakajima Y, Zhou J, Li BZ, Shi YH, Xiao YS, Xu Y, Fan J. Overexpression of PD-L1 significantly associates with tumor aggressiveness and postoperative recurrence in human hepatocellular carcinoma. Clin Cancer Res. 2009 Feb 1;15(3):971-9. doi: 10.1158/1078-0432.CCR-08-1608.

  PMID: 19188168 BACKGROUND

• Yang CY, Lin MW, Chang YL, Wu CT, Yang PC. Programmed cell death-ligand 1 expression in surgically resected stage I pulmonary adenocarcinoma and its correlation with driver mutations and clinical outcomes. Eur J Cancer. 2014 May;50(7):1361-9. doi: 10.1016/j.ejca.2014.01.018. Epub 2014 Feb 15.

  PMID: 24548766 BACKGROUND

• Madore J, Vilain RE, Menzies AM, Kakavand H, Wilmott JS, Hyman J, Yearley JH, Kefford RF, Thompson JF, Long GV, Hersey P, Scolyer RA. PD-L1 expression in melanoma shows marked heterogeneity within and between patients: implications for anti-PD-1/PD-L1 clinical trials. Pigment Cell Melanoma Res. 2015 May;28(3):245-53. doi: 10.1111/pcmr.12340. Epub 2014 Dec 22.

  PMID: 25477049 BACKGROUND

• Muenst S, Schaerli AR, Gao F, Daster S, Trella E, Droeser RA, Muraro MG, Zajac P, Zanetti R, Gillanders WE, Weber WP, Soysal SD. Expression of programmed death ligand 1 (PD-L1) is associated with poor prognosis in human breast cancer. Breast Cancer Res Treat. 2014 Jul;146(1):15-24. doi: 10.1007/s10549-014-2988-5. Epub 2014 May 20.

  PMID: 24842267 BACKGROUND

• Shi F, Shi M, Zeng Z, Qi RZ, Liu ZW, Zhang JY, Yang YP, Tien P, Wang FS. PD-1 and PD-L1 upregulation promotes CD8(+) T-cell apoptosis and postoperative recurrence in hepatocellular carcinoma patients. Int J Cancer. 2011 Feb 15;128(4):887-96. doi: 10.1002/ijc.25397.

  PMID: 20473887 BACKGROUND

• Heeren AM, Punt S, Bleeker MC, Gaarenstroom KN, van der Velden J, Kenter GG, de Gruijl TD, Jordanova ES. Prognostic effect of different PD-L1 expression patterns in squamous cell carcinoma and adenocarcinoma of the cervix. Mod Pathol. 2016 Jul;29(7):753-63. doi: 10.1038/modpathol.2016.64. Epub 2016 Apr 8.

  PMID: 27056074 BACKGROUND

• Lim SH, Hong M, Ahn S, Choi YL, Kim KM, Oh D, Ahn YC, Jung SH, Ahn MJ, Park K, Zo JI, Shim YM, Sun JM. Changes in tumour expression of programmed death-ligand 1 after neoadjuvant concurrent chemoradiotherapy in patients with squamous oesophageal cancer. Eur J Cancer. 2016 Jan;52:1-9. doi: 10.1016/j.ejca.2015.09.019. Epub 2015 Nov 26.

  PMID: 26623522 BACKGROUND

• Zhang J, Fang W, Qin T, Yang Y, Hong S, Liang W, Ma Y, Zhao H, Huang Y, Xue C, Huang P, Hu Z, Zhao Y, Zhang L. Co-expression of PD-1 and PD-L1 predicts poor outcome in nasopharyngeal carcinoma. Med Oncol. 2015 Mar;32(3):86. doi: 10.1007/s12032-015-0501-6. Epub 2015 Feb 22.

  PMID: 25702326 BACKGROUND

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

Cisplatin; Radiotherapy

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Therapeutics

Study Officials

• You Lu, MD

  West China Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chair of Department of Thoracic Oncology

Study Record Dates

• First Submitted: April 9, 2018
• First Posted: June 18, 2018
• Study Start: October 1, 2016
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: January 22, 2019

Record last verified: 2019-01

Locations

CN (2)