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

Advanced Biliary Tract Cancer Clinical Trial

Official title:

Hepatic Arterial Infusion Chemotherapy With Oxaliplatin, 5-fluorouracil and Bevacizumab Plus Intravenous Toripalimab for Advanced Biliary Tract Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04217954
• Other study ID #: FIBTC
• Status: Completed
• Phase: Phase 2
• Start date: July 28, 2020
• Est. completion date: June 1, 2023

Study information

• Verified date: June 2023
• Source: Peking University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: June 1, 2023
• Est. primary completion date: May 19, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Biliary tract cancer proved by histology or cytology

2. Metastatic advanced or locally advanced unresectable biliary tract cancer, including gallbladder cancer, intrahepatic cholangiocarcinoma and perihilar cholangiocarcinoma, decided by hepatobiliary doctor and radiologist.

3. At least one measurable lesion within liver;

4. No prior intra-arterial/systemic chemotherapy or other systemic therapies

5. Prior resection, TACE or ablation will be allowed.

6. Age from 18 years old to 80 years old.

7. the performance of Eastern Cooperative Oncology Group (ECOG) <2

8. Child-Pugh A or Child-Pugh B (= score 7).

9. Expectant survival time = 3 months.

10. Baseline blood count test and blood biochemical must meet following criteria:

1. Hemoglobin = 90 g/L;

2. Absolute neutrophil count = 1.5×10^9/L;

3. Blood platelet count = 100×10^9/L;

4. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) = 2.5 times of upper limit of normal (ULN);

5. Total bilirubin = 2 times of ULN;

6. Serum creatinine = 1.5 times of ULN;

7. Albumin = 30 g/L.

11. Patients sign informed consent.

Exclusion Criteria:

1. Distal cholangiocarcinoma.

2. Allergic to contrast agent.

3. Pregnant or lactational.

4. Allergic to 5-fluorouracil, or have metabolic disorder of 5-fluorouracil.

5. More than 80 years old.

6. Previous systematic chemotherapy or radiotherapy.

7. Child-Pugh C or Child-Pugh B (= score 8).

8. Coinstantaneous a lot of malignant hydrothorax or ascites.

9. History of organ transplantation (including bone marrow auto-transplantation and peripheral stem cell transplantation).

10. Coinstantaneous infection and need anti-infection therapy.

11. 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).

12. Coinstantaneous peripheral nervous system disorder or with history of obvious mental disorder and central nervous system disorder.

13. Diagnosed other kinds of malignant within 5 years, except for non-melanoma skin cancer and carcinoma in situ of cervix.

14. Without legal capacity.

15. Impact the study because of medical or ethical reasons.

16. Uncorrectable coagulation disorder.

17. Obvious abnormal in ECG or obvious clinical symptoms of heart disease, like congestive heart failure (CHF), coronary heart disease with obvious clinical symptoms, unmanageable arrhythmia and hypertension.

18. History of myocardial infarction within 12 months, or Grade III/IV of heart function.

19. Severe liver disease (like cirrhosis), renal disease, respiratory disease, unmanageable diabetes or other kinds of systematic disease.

Related Conditions & MeSH terms

• Advanced Biliary Tract Cancer
• Biliary Tract Neoplasms

Intervention

Drug:
• OXA, 5-FU and bevacizumab plus Toripalimab
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. Maintenance treatment: Bevacizumab (300mg) + PD-1 inhibitor (Toripalimab 240mg) will be given intravenously, every 3 weeks.

Locations

Country	Name	City	State
China	Peking University Cancer Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking University

Country where clinical trial is conducted

China, 

References & Publications (9)

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. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall survival	date from the start of treatment until death or lost to follow-up, whichever happen first, assessed at least 6 months	From the start of treatment until death or lost to follow-up, up to approximately 3 years
Secondary	Adverse events	type and incidence of adverse events	From the start of treatment until the end of treatment, up to approximately 3 years
Secondary	Progression-free survival	date from the first treatment to the date of disease progression, lost to follow-up or death, whichever happen first	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