Toripalimab Combined With Gemcitabine/5--fluoropyrimidine for Advanced Cholangiocarcinoma

Advanced Cholangiocarcinoma Clinical Trial

Official title:

Clinical Study of Toripalimab Monoclonal Antibody Combined With Gemcitabine/5--fluoropyrimidine in the Treatment of Advanced Cholangiocarcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03982680
• Other study ID #: cholangiocarcinoma
• Status: Recruiting
• Phase: Phase 2
• Start date: July 13, 2019
• Est. completion date: December 30, 2021

Study information

• Verified date: July 2019
• Source: Jiangmen Central Hospital
• Contact: Deng wenjing, master
• Phone: (+86)07503165905
• Email: wjdeng2011[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study is a phase II clinical trial of single arm. The purpose is to evaluate the safety and efficacy of anti-PD-1 antibody Toripalimab combined with chemotherapy(gemcitabine+5-fluorine pyrimidine) in unresectable advanced cholangiocarcinoma patients.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 30, 2021
• Est. primary completion date: May 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• histologically or cytologically confirmed cholangiocarcinoma

• stage IV disease,no system therapy for advanced disease

• one or more lesions that can be measured by imaging assessment

• 18 to 70 years of age and life expectancy exceeds 3 months

• adequate specimens for detection of PD-1/PD-L1 and MMR

• karnofsky performance status(KPS) score =70%

• routine blood routine, liver and kidney function and electrocardiogram were basically normal without contraindication of chemotherapy.

Exclusion Criteria:

• dual cancers other than cholangiocarcinoma

• metastasis of central nervous system

• unreleased biliary obstruction

• acute infections requiring treatment

• non-infectious pneumonia requires glucocorticoid therapy, active autoimmune diseases, or systemic immunosuppressive therapy.

Related Conditions & MeSH terms

• Advanced Cholangiocarcinoma
• Cholangiocarcinoma

Intervention

Drug:
• Toripalimab
3mg/kg on d1 and d15 q4W*4cycles,then 3mg/kg q3w for 1 year in total
• Gemcitabine
1250mg/m2 on d1 and d15 q4W*4cycles
• 5- fluorine pyrimidine
400mg/m2 intravenous injection plus 5-FU 2.4g-3.6g/m2 continuous intravenous drip for 48h on d1 and d15 q4W*4cycles

Locations

Country	Name	City	State
China	Jiangmen central hospital	Jiangmen	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Jiangmen Central Hospital

Country where clinical trial is conducted

China, 

References & Publications (12)

Asaoka Y, Ijichi H, Koike K. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med. 2015 Nov 12;373(20):1979. doi: 10.1056/NEJMc1510353. — View Citation

GBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015 Jan 10;385(9963):117-71. doi: 10.1016/S0140-6736(14)61682-2. Epub 2014 Dec 18. — View Citation

Gotwals P, Cameron S, Cipolletta D, Cremasco V, Crystal A, Hewes B, Mueller B, Quaratino S, Sabatos-Peyton C, Petruzzelli L, Engelman JA, Dranoff G. Prospects for combining targeted and conventional cancer therapy with immunotherapy. Nat Rev Cancer. 2017 May;17(5):286-301. doi: 10.1038/nrc.2017.17. Epub 2017 Mar 24. Review. — View Citation

Gou M, Zhang Y, Si H, Dai G. Efficacy and safety of nivolumab for metastatic biliary tract cancer. Onco Targets Ther. 2019 Jan 25;12:861-867. doi: 10.2147/OTT.S195537. eCollection 2019. — View Citation

Herbst RS, Soria JC, Kowanetz M, Fine GD, Hamid O, Gordon MS, Sosman JA, McDermott DF, Powderly JD, Gettinger SN, Kohrt HE, Horn L, Lawrence DP, Rost S, Leabman M, Xiao Y, Mokatrin A, Koeppen H, Hegde PS, Mellman I, Chen DS, Hodi FS. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014 Nov 27;515(7528):563-7. doi: 10.1038/nature14011. — View Citation

Jain A, Javle M. Molecular profiling of biliary tract cancer: a target rich disease. J Gastrointest Oncol. 2016 Oct;7(5):797-803. Review. — View Citation

Morizane C, Ueno M, Ikeda M, Okusaka T, Ishii H, Furuse J. New developments in systemic therapy for advanced biliary tract cancer. Jpn J Clin Oncol. 2018 Aug 1;48(8):703-711. doi: 10.1093/jjco/hyy082. Review. — View Citation

Okusaka T, Nakachi K, Fukutomi A, Mizuno N, Ohkawa S, Funakoshi A, Nagino M, Kondo S, Nagaoka S, Funai J, Koshiji M, Nambu Y, Furuse J, Miyazaki M, Nimura Y. Gemcitabine alone or in combination with cisplatin in patients with biliary tract cancer: a comparative multicentre study in Japan. Br J Cancer. 2010 Aug 10;103(4):469-74. doi: 10.1038/sj.bjc.6605779. Epub 2010 Jul 13. — View Citation

Sabbatino F, Villani V, Yearley JH, Deshpande V, Cai L, Konstantinidis IT, Moon C, Nota S, Wang Y, Al-Sukaini A, Zhu AX, Goyal L, Ting DT, Bardeesy N, Hong TS, Fernandez-del Castillo C, Tanabe KK, Lillemoe KD, Ferrone S, Ferrone CR. PD-L1 and HLA Class I Antigen Expression and Clinical Course of the Disease in Intrahepatic Cholangiocarcinoma. Clin Cancer Res. 2016 Jan 15;22(2):470-8. doi: 10.1158/1078-0432.CCR-15-0715. Epub 2015 Sep 15. — View Citation

Takakura H, Domae S, Ono T, Sasaki A. The Immunological Impact of Chemotherapy on the Tumor Microenvironment of Oral Squamous Cell Carcinoma. Acta Med Okayama. 2017 Jun;71(3):219-226. doi: 10.18926/AMO/55204. — View Citation

Taube JM, Klein A, Brahmer JR, Xu H, Pan X, Kim JH, Chen L, Pardoll DM, Topalian SL, Anders RA. Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy. Clin Cancer Res. 2014 Oct 1;20(19):5064-74. doi: 10.1158/1078-0432.CCR-13-3271. Epub 2014 Apr 8. — View Citation

Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012 Jun 28;366(26):2443-54. doi: 10.1056/NEJMoa1200690. Epub 2012 Jun 2. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	the value of PD-1/PD-L1	to analyze the predictive value of PD-1/PD-L1 for efficacy and toxicity	from the beginning of the first line systemic therapy until the end of follow-up,assessed up to 24 months
Other	the value of MMR	to analyze the predictive value of MMR for efficacy and toxicity	from the beginning of the first line systemic therapy until the end of follow-up,assessed up to 24 months
Primary	6-month PFS rate	the rate of 6-month progression free survival	6-month after the beginning of first line systemic therapy
Primary	mPFS	the median of progression free survival	from the beginning of the first line systemic therapy until the date of first documented progression or date of death from any cause,whichever came first,assessed up to 24 months
Primary	Toxic side effects	assess according to the National Cancer Institute-Common Terminology Criteria for Adverse Events 3.0	from the beginning of the first line systemic therapy until the end of follow-up,assessed up to 24 months
Secondary	ORR	the objective response rate	from the beginning of the first line systemic therapy until the date of completion of therapy,assessed up to 13 months
Secondary	DCR	the disease control rate	from the beginning of the first line systemic therapy until the date of completion of therapy,assessed up to 13 months
Secondary	1-year OS rate	the rate of 1-year overall survival	1 year after the beginning of the first line systemic therapy
Secondary	mOS	the median of overall survival	from the beginning of the first line systemic therapy until the date of death from any cause,assessed up to 24 months