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

Study Overview
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Brief Summary
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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.

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

Conditions
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Advanced Biliary Tract Cancer

Intervention / Treatment
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* Drug: OXA, 5-FU and bevacizumab plus Toripalimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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; Serum creatinine ≤ 1.5 times of ULN; Albumin ≥ 30 g/L. Patients sign informed consent. Exclusion Criteria: 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. Uncorrectable coagulation disorder. 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. History of myocardial infarction within 12 months, or Grade III/IV of heart function. Severe liver disease (like cirrhosis), renal disease, respiratory disease, unmanageable diabetes or other kinds of systematic disease.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OXA, 5-FU and Bev plus Toripalimab<br>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<br>* 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.<br>* Other names: FOLFOX;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Adverse events | type and incidence of adverse events | From the start of treatment until the end of treatment, up to approximately 3 years | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hepatic arterial infusion chemotherapy, oxaliplatin, 5-fluorouracil, bevacizumab, Toripalimab, advanced biliary tract cancer