HAIC Combined With Toripalimab and Donafenib for Advanced BTC

Biliary Tract Adenocarcinoma Clinical Trial

Official title:

Phase II Study to Evaluate the Efficacy and Safety of HAIC Combined With Toripalimab and Donafenib in Patients With Advanced Biliary Tract Cancer

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05350943
• Other study ID #: 2021-GZWK-04
• Status: Enrolling by invitation
• Phase: Phase 2
• Start date: March 1, 2022
• Est. completion date: November 2023

Study information

• Verified date: October 2022
• Source: Fudan University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a single center, single arm, phase II, prospective study to evaluate the efficacy and safety of Hepatic Arterial Infusion Chemotherapy (HAIC) combined with PD-1 inhibitor immunotherapy Toripalimab and Tyrosine Kinase Inhibitor Donafenib in patients with advanced biliary tract cancer.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 70
• Est. completion date: November 2023
• Est. primary completion date: November 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• 18 to 80 years of age, of any sex;

• Histologically/Cytologically confirmed diagnosis of unresectable advanced adenocarcinoma of the gallbladder, intrahepatic bile duct and extrahepatic bile duct.

• At least one measurable lesion umder CT/MRI as defined by RECIST1.1 criteria

• Patients must have adequate organ and marrow function as defined below:

Blood test:

Hemoglobin (HB) =90 g/L Absolute neutrophil count (ANC) =1.5×10^9/L; Platelet (PLT) =80×10^9/L;

Biochemical test:

total bilirubin=2×ULN (institutional upper limit of norm) AST(SGOT)/ALT(SGPT)=2.5 ×ULN creatinine clearance= 50 ml/min as calculated by the Cockroft-Gault formula

• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0-1;

• Indocyanine Green Retention Rates at 15 min (ICGR15<22%;

• Life expectancy of > 3 months;

Exclusion Criteria

• Patients with other malignant tumors should be excluded

• Female patients who are pregnant or breast-feeding. Female patients who are pregnant during the study should also exit.

• Patient has enter any other clinical trails within 4 weeks prior to study entry.

• Patient known with a severe and/or uncontrolled medical disease.

• Chronic non-healing wound/bone fracture

• History of organ transplant

• Patients with abnormal coagulation function (PT>16s, APTT>43s, TT>21s, Fbg<2g/L), those have bleeding tendency (14 days prior to randomization must meet: INR is within the normal range without any use of anticoagulants); patients treated with anticoagulants or vitamin K antagonists such as warfarin, heparin or analogous therapy; use for preventive purposes is permitted provided that the international normalized ratio of prothrombin time (INR) = 1.5, take low-dose warfarin (1 mg PO, QD) or low-dose aspirin (do not exceed 100 mg per day);

• Previous history of aterial/venous thrombosis such as cerebrovascular accidents, pulmonary embolism or deep venous thrombosis within one year prior to patients recruitment.

• Hitstory of psychiatric drug abuse and hasn't come clean, or with psychiatric illness/social situations that would limit compliance with study requirements

• History of immunodeficiency, or other acquired/congenital immunodeficiency diseases

• Concomitant diseases that severely endanger the safety of the subject or affect the study completion according to the judgment of the investigator

• Willingness to sign a written informed consent document, with good compliance.

Related Conditions & MeSH terms

• Adenocarcinoma
• Biliary Tract Adenocarcinoma

Intervention

Procedure:
• HAIC
After successful percutaneous hepatic artery cannulation, superior mesenteric arteriogram and hepatic arteriogram were performed, and after confirming that the subjects were eligible for enrollment according to the results, the hepatic artery was cannulated to the predetermined position. The catheter was connected to a syringe pump in the ward for continuous pumping of drugs.

Drug:
• Gemcitabine
1000 mg/m^2 in 100ml saline solution IV, d1, Q3W
• Oxaliplatin
85 mg/m^2 in 500ml 5% glucose solution over 2 hours IV, d1, Q3W
• Toripalimab
3mg/kg (body weight < 60kg) or 240 mg(body weight>= 60kg)in 250 saline soluation, IV, Q3W
• Donafenib
0.2mg. P.O, BID, continuously

Locations

Country	Name	City	State
China	Fudan University Shanghai Cancer Center	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Lu Wang, MD, PhD

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate (ORR)	the sum of complete response rate and partial response rate	through study completion, an average of 2 year
Secondary	Disease Control rate (DCR)	the sum of complete response rate, partial response rate and stable disease rate	through study completion, an average of 2 year
Secondary	Progression-free survival (PFS)	Time from randomization to disease progression	through study completion, an average of 2 year
Secondary	Overall survival (OS)	Time from randomization to death for any cause	through study completion, an average of 2 year
Secondary	Number of participants with treatment-related adverse events as assessed by NCI CTCAE v4.0.	Unforeseen medical events occurred when the subjects received drug treatment or research, but there is not necessarily a causal relationship with the drugs used.; Severe adverse events	through study completion, an average of 2 year
Secondary	Quality of life questionnaire	The concept of comprehensively evaluating the quality of life	through study completion, an average of 2 year