HAIC Combined With Toripalimab and Donafenib for Advanced BTC

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

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Biliary Tract Adenocarcinoma
• Intervention / Treatment: Procedure: HAIC; Drug: Gemcitabine; Drug: Oxaliplatin; Drug: Toripalimab; Drug: Donafenib

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 200062
    • Fudan University Shanghai Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: HAIC+Toripalimab+Donafenib; HAIC(GEMOX)+Toripalimab+Donafenib

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	the sum of complete response rate and partial response rate	through study completion, an average of 2 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Progression-free survival (PFS)	Time from randomization to disease progression	through study completion, an average of 2 year
Overall survival (OS)	Time from randomization to death for any cause	through study completion, an average of 2 year
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
Quality of life questionnaire	The concept of comprehensively evaluating the quality of life	through study completion, an average of 2 year

Collaborators and Investigators

• Sponsor: Lu Wang, MD, PhD

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2022
• Primary Completion (Anticipated): November 1, 2022
• Study Completion (Anticipated): November 1, 2023

Study Registration Dates

• First Submitted: March 24, 2022
• First Submitted That Met QC Criteria: April 27, 2022
• First Posted (Actual): April 28, 2022

Study Record Updates

• Last Update Posted (Actual): October 18, 2022
• Last Update Submitted That Met QC Criteria: October 17, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine; Oxaliplatin
• Other Study ID Numbers: 2021-GZWK-04

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No