HAIC With Oxaliplatin, 5-FU and Bevacizumab Plus Intravenous Toripalimab for Advanced BTC

NCT04217954 | Completed Phase 2

• 1 other identifier: FIBTC
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

Hepatic arterial infusion chemotherapy (HAIC) deliver high concentration of chemotherapeutic agents directly to the liver tumor, was proved to be effective for intrahepatic and perihilar cholangiocarcinoma. Based on the potential synergistic effect of bevacizumab, chemotherapy and PD-1 inhibitor, this phase II clinical study want to test the efficacy and safety using intra-arterial infusion of oxaliplatin, 5-fluorouracil and bevacizumab combined with intravenous infusion of PD-1 inhibitor (Toripalimab) in the treatment of unresectable biliary malignant tumors.

Conditions

Advanced Biliary Tract Cancer

Keywords

hepatic arterial infusion chemotherapy; oxaliplatin; 5-fluorouracil; bevacizumab; Toripalimab; advanced biliary tract cancer

Outcome Measures

Primary Outcomes (1)

• Overall response rate

  CR plus PR according to imRECIST

  From the start of treatment until the end of treatment, up to approximately 3 years

Secondary Outcomes (3)

• Overall survival

  From the start of treatment until death or lost to follow-up, up to approximately 3 years

• Adverse events

  From the start of treatment until the end of treatment, up to approximately 3 years

• Progression-free survival

  From the start of the treatment until first documented progression or death from any cause, whichever came first, assessed up to approximately 3 yearsse date of disease progression

Study Arms (1)

OXA, 5-FU and Bev plus Toripalimab

EXPERIMENTAL

the patients enrolled in this arm would receive hepatic arterial infusion chemotherapy with oxaliplatin, 5-fluorouracil and bevacizumab plus intravenous Toripalimab

Drug: OXA, 5-FU and bevacizumab plus Toripalimab

Interventions

OXA, 5-FU and bevacizumab plus Toripalimab DRUG

1. concomitant treatment: A. HAIC: oxaliplatin (40 mg/m2 for 2 hours), 5-fluorouracil (800 mg/ m2 for 22 hours) on days 1-3, and arterial bevacizumab 300mg for 2 hours on d1 before oxaliplatin through a percutaneously implanted port-catheter system. B. Intravenous PD-1 inhibitor (Toripalimab) 240 mg for 30-60 minutes on d1 before the HAIC. The concomitant treatment repeat every three week, up to 6 cycles. 2. Maintenance treatment: Bevacizumab (300mg) + PD-1 inhibitor (Toripalimab 240mg) will be given intravenously, every 3 weeks.

Also known as: FOLFOX

OXA, 5-FU and Bev plus Toripalimab

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Biliary tract cancer proved by histology or cytology
• Metastatic advanced or locally advanced unresectable biliary tract cancer, including gallbladder cancer, intrahepatic cholangiocarcinoma and perihilar cholangiocarcinoma, decided by hepatobiliary doctor and radiologist.
• At least one measurable lesion within liver;
• No prior intra-arterial/systemic chemotherapy or other systemic therapies
• Prior resection, TACE or ablation will be allowed.
• Age from 18 years old to 80 years old.
• the performance of Eastern Cooperative Oncology Group (ECOG) \<2
• Child-Pugh A or Child-Pugh B (≤ score 7).
• Expectant survival time ≥ 3 months.
• Baseline blood count test and blood biochemical must meet following criteria:
• Hemoglobin ≥ 90 g/L;
• Absolute neutrophil count ≥ 1.5×10\^9/L;
• Blood platelet count ≥ 100×10\^9/L;
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤ 2.5 times of upper limit of normal (ULN);
• Total bilirubin ≤ 2 times of ULN;

You may not qualify if:

• Distal cholangiocarcinoma.
• Allergic to contrast agent.
• Pregnant or lactational.
• Allergic to 5-fluorouracil, or have metabolic disorder of 5-fluorouracil.
• More than 80 years old.
• Previous systematic chemotherapy or radiotherapy.
• Child-Pugh C or Child-Pugh B (≥ score 8).
• Coinstantaneous a lot of malignant hydrothorax or ascites.
• History of organ transplantation (including bone marrow auto-transplantation and peripheral stem cell transplantation).
• Coinstantaneous infection and need anti-infection therapy.
• Hepatitis B virus DNA load ≥ 100 IU/ml (patients whose hepatitis B virus DNA load decreased to \< 100 IU/ml after anti-virus therapy could be enrolled).
• Coinstantaneous peripheral nervous system disorder or with history of obvious mental disorder and central nervous system disorder.
• Diagnosed other kinds of malignant within 5 years, except for non-melanoma skin cancer and carcinoma in situ of cervix.
• Without legal capacity.
• Impact the study because of medical or ethical reasons.

Sponsors & Collaborators

• Peking University: lead

Study Sites (1)

Peking University Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

Related Publications (9)

• Park J, Kim MH, Kim KP, Park DH, Moon SH, Song TJ, Eum J, Lee SS, Seo DW, Lee SK. Natural History and Prognostic Factors of Advanced Cholangiocarcinoma without Surgery, Chemotherapy, or Radiotherapy: A Large-Scale Observational Study. Gut Liver. 2009 Dec;3(4):298-305. doi: 10.5009/gnl.2009.3.4.298. Epub 2009 Dec 31.

  PMID: 20431764 BACKGROUND

• Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, Madhusudan S, Iveson T, Hughes S, Pereira SP, Roughton M, Bridgewater J; ABC-02 Trial Investigators. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010 Apr 8;362(14):1273-81. doi: 10.1056/NEJMoa0908721.

  PMID: 20375404 BACKGROUND

• Boehm LM, Jayakrishnan TT, Miura JT, Zacharias AJ, Johnston FM, Turaga KK, Gamblin TC. Comparative effectiveness of hepatic artery based therapies for unresectable intrahepatic cholangiocarcinoma. J Surg Oncol. 2015 Feb;111(2):213-20. doi: 10.1002/jso.23781. Epub 2014 Sep 1.

  PMID: 25176325 BACKGROUND

• Wang X, Hu J, Cao G, Zhu X, Cui Y, Ji X, Li X, Yang R, Chen H, Xu H, Liu P, Li J, Li J, Hao C, Xing B, Shen L. Phase II Study of Hepatic Arterial Infusion Chemotherapy with Oxaliplatin and 5-Fluorouracil for Advanced Perihilar Cholangiocarcinoma. Radiology. 2017 May;283(2):580-589. doi: 10.1148/radiol.2016160572. Epub 2016 Nov 7.

  PMID: 27820684 BACKGROUND

• Gao F, Yang C. Anti-VEGF/VEGFR2 Monoclonal Antibodies and their Combinations with PD-1/PD-L1 Inhibitors in Clinic. Curr Cancer Drug Targets. 2020;20(1):3-18. doi: 10.2174/1568009619666191114110359.

  PMID: 31729943 BACKGROUND

• Hegde PS, Wallin JJ, Mancao C. Predictive markers of anti-VEGF and emerging role of angiogenesis inhibitors as immunotherapeutics. Semin Cancer Biol. 2018 Oct;52(Pt 2):117-124. doi: 10.1016/j.semcancer.2017.12.002. Epub 2017 Dec 8.

  PMID: 29229461 BACKGROUND

• Mathew M, Enzler T, Shu CA, Rizvi NA. Combining chemotherapy with PD-1 blockade in NSCLC. Pharmacol Ther. 2018 Jun;186:130-137. doi: 10.1016/j.pharmthera.2018.01.003. Epub 2018 Jan 31.

  PMID: 29352857 BACKGROUND

• Dalgleish AG. Rationale for combining immunotherapy with chemotherapy. Immunotherapy. 2015;7(3):309-16. doi: 10.2217/imt.14.111.

  PMID: 25804482 BACKGROUND

• Longo V, Brunetti O, Azzariti A, Galetta D, Nardulli P, Leonetti F, Silvestris N. Strategies to Improve Cancer Immune Checkpoint Inhibitors Efficacy, Other Than Abscopal Effect: A Systematic Review. Cancers (Basel). 2019 Apr 15;11(4):539. doi: 10.3390/cancers11040539.

  PMID: 30991686 BACKGROUND

MeSH Terms

Interventions

Fluorouracil; Bevacizumab; toripalimab; Folfox protocol

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Xiaodong Wang, MD

  Department of Interventional Therapy, Peking University Cancer Hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 1, 2020
• First Posted: January 6, 2020
• Study Start: July 28, 2020
• Primary Completion: May 19, 2023
• Study Completion: June 1, 2023
• Last Updated: June 23, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)