Clinical trial NCT04217954: HAIC With Oxaliplatin, 5-FU and Bevacizumab Plus Intravenous Toripalimab for Advanced BTC
Official title: Hepatic Arterial Infusion Chemotherapy With Oxaliplatin, 5-fluorouracil and Bevacizumab Plus Intravenous Toripalimab for Advanced Biliary Tract Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Advanced Biliary Tract Cancer
Keywords: hepatic arterial infusion chemotherapy
oxaliplatin
5-fluorouracil
bevacizumab
Toripalimab
advanced biliary tract cancer
Lead sponsor: Peking University
Sponsor class: OTHER
First posted: 2020-01-06
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Overall response rate
timeFrame: From the start of treatment until the end of treatment, up to approximately 3 years
Secondary outcomes:
measure: Overall survival
timeFrame: From the start of treatment until death or lost to follow-up, up to approximately 3 years
measure: Adverse events
timeFrame: From the start of treatment until the end of treatment, up to approximately 3 years
measure: Progression-free survival
timeFrame: 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
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Cancer Hospital
state: Beijing
Study officials:
affiliation: Department of Interventional Therapy, Peking University Cancer Hospital
name: Xiaodong Wang, MD
role: STUDY_DIRECTOR
References:
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.
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.
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