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

A study testing Cisplatin in people with Cervical Cancer, run by Sichuan University at 2 sites in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Trial 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… Read more about this study

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Cervical Cancer
What is being tested?: Cisplatin
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 58 participants
Where: 2 sitesChina
Study dates: Oct 2016to Dec 2019
Phase: Interventional
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

2 sites in 1 country.

China2 sites

West China Hospital, Sichuan University
Chengdu, Sichuan, 610041
Guizhou Province People's Hospital
Guizhou, Guizhou

Other trials in China

About this study

Official title: A Prospective Study of Dynamic Monitoring Specific Immune Response in Locally Advanced Cervix Cancer After Radio-chemotherapy

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.

Read the 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.

Conditions: Cervical Cancer
Being tested: Cisplatin
Keywords: Cervical Cancer, PD-L1, Concurrent Chemoradiotherapy
Medical subject headings: Uterine Cervical Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CisplatinDrug
Also called radiotherapy
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).

Study groups in NCT03559803
Study group	Role	What they receive
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. Receives: Drug: Cisplatin

What is being measured

The primary outcome is the main question the study is designed to answer.

The change of expression of PD-L1+ on cervix biopsies
The biopsy was collected at baseline,3 weeks,2 months
Measured: 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
The blood was collected at baseline,3 weeks,2 months
Measured: baseline,3 weeks,2 months
The diversity of T-cell Repertoire in cervix biopsies and blood, respectively
The blood and biopsies were collected at baseline,3 weeks,2 months
Measured: baseline,3 weeks,2 months
The change of expression of CD8+PD1+ lymphocytes infiltrate on cervix biopsies
The biopsy was collected at baseline,3 weeks,2 months
Measured: baseline,3 weeks,2 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 2016Dec 2019

First posted18 Jun 2018
Study startOct 2016
Primary completionDec 2019 (estimated)
Study completionDec 2019 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (10)Papers the sponsor has linked to this study.
Other trials for Cervical CancerStudies of the same condition, open and under way.
More trials run by Sichuan UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 58 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03559803
Sponsor's protocol ID: GHR-002
Status last verified: Jan 2019
First submitted: 9 Apr 2018
Last updated: 22 Jan 2019
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Undecided

Publications

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.
PubMed 19901438
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.
PubMed 19931186
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.
PubMed 19188168
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.
PubMed 24548766
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.
PubMed 25477049
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.
PubMed 24842267
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.
PubMed 20473887
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.
PubMed 27056074
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.
PubMed 26623522
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.
PubMed 25702326

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Cervical Cancer trials

Study at a glance

From the registry record, last updated by the sponsor on 22 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Prospective Study of Dynamic Monitoring Specific Immune Response in Locally Advanced Cervix Cancer After Radio-chemotherapy
ClinicalTrials.gov ID: NCT03559803
Acronym / sponsor ID: GHR-002
Conditions: Cervical Cancer
Keywords: Cervical Cancer, PD-L1, Concurrent Chemoradiotherapy
Study type: Interventional
Recruitment status: Unknown status
Enrolment: 58 participants (actual)
Lead sponsor: Sichuan UniversityUniversity, hospital or other
Study start: Oct 2016 (actual)
Primary completion: Dec 2019 (estimated)
Study completion: Dec 2019 (estimated)
First posted: 18 Jun 2018 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Perspectives:

To analyse if the change of specific immune response will correlate with clinical effect of advanced cervix cancer after radio-chemotherapy.

Detailed description

To analyse if the change of specific immune response will correlate with clinical effect of advanced cervix cancer after radio-chemotherapy.

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 design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Cisplatin	Experimental	Drug: CisplatinWeekly 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.

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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

Key exclusion criteria (7 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CisplatinAlso: radiotherapyDrug: 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).	Drug	Cisplatin

Primary outcome

The change of expression of PD-L1+ on cervix biopsies
Time frame: From baseline,3 weeks,2 months
The biopsy was collected at baseline,3 weeks,2 months

3 secondary outcomes

The change of expression of PD1 on the non-regulatory CD4+ and CD8+ lymphocytes and Treg cells
Time frame: baseline,3 weeks,2 months
The diversity of T-cell Repertoire in cervix biopsies and blood, respectively
Time frame: baseline,3 weeks,2 months
The change of expression of CD8+PD1+ lymphocytes infiltrate on cervix biopsies
Time frame: baseline,3 weeks,2 months

Results and safety

Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2019.
Background: PubMed 19901438Jayshree RS, Sreenivas A, Tessy M, Krishna S. Cell intrinsic & extrinsic factors in cervical carcinogenesis. Indian J Med Res. 2009 Sep;130(3):286-95.
Background: PubMed 19931186Folkl 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.
Background: PubMed 19188168Gao 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.
Background: PubMed 24548766Yang 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.
Background: PubMed 25477049Madore 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.
Background: PubMed 24842267Muenst 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.
Background: PubMed 20473887Shi 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.
Background: PubMed 27056074Heeren 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.
Background: PubMed 26623522Lim 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.
Background: PubMed 25702326Zhang 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.
Individual participant dataSharing planned: Undecided

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

You Lu, MD principal investigator

West China Hospital

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Cisplatin in people with Cervical Cancer, run by Sichuan University at 2 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 22 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The change of expression of PD-L1+ on cervix biopsies (time frame: From baseline,3 weeks,2 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03559803, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2019.