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

Sponsor

Peking University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04217954

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Biliary Tract Cancer	Drug: OXA, 5-FU and bevacizumab plus Toripalimab	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

32 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jul 28, 2020

Anticipated Primary Completion Date :

Jul 28, 2022

Anticipated Study Completion Date :

Jul 28, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: OXA, 5-FU and Bev plus Toripalimab 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 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. Other Names: FOLFOX

Arm

Intervention/Treatment

Experimental: OXA, 5-FU and Bev plus Toripalimab

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

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.

Other Names:

FOLFOX

Outcome Measures

Primary Outcome Measures

Progression-free survival [From the start of treatment until disease progression, lost to follow-up or death, up to approximately 3 years]
date from the first treatment until disease progression, lost to follow-up or death, whichever happen first, assessed at least 2 months
Overall response rate [From the start of treatment until the end of treatment, up to approximately 3 years]
CR plus PR according to imRECIST

Secondary Outcome Measures

Overall survival [From the start of treatment until death or lost to follow-up, up to approximately 3 years]
date from the start of treatment until death or lost to follow-up, whichever happen first, assessed at least 6 months
Adverse events [From the start of treatment until the end of treatment, up to approximately 3 years]
type and incidence of adverse events
CA 19-9 level [From the start of treatment until the end of treatment, up to approximately 3 years]
The change of CA 19-9 before and after the treatment
The signal in dynamic contrast enhanced (DCE)-MRI [From the start of treatment until the end of treatment, up to approximately 3 years]
The change of signal in DCE-MRI before and after the treatment
The change in diffusion weighted imaging (DWI) of MRI [From the start of treatment until the end of treatment, up to approximately 3 years]
The change in DWI of MRI, including apparent diffusion coefficient (ADC), before and after the treatment

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.