FOLFOX-HAIC Combined With Donafenib and Pucotenlimab as First-Line Treatment for Unresectable Intrahepatic Cholangiocarcinoma

NOT YET RECRUITING

NCT07353827

PHASE2

Sponsor: Sun Yat-sen University

Summary

This is a prospective, open-label, single-arm phase II study designed to evaluate the efficacy and safety of FOLFOX-based hepatic arterial infusion chemotherapy (HAIC) in combination with donafenib and pucotenlimab as first-line treatment in patients with unresectable intrahepatic cholangiocarcinoma. Eligible patients will receive FOLFOX-HAIC administered every three weeks together with oral donafenib and intravenous pucotenlimab. Tumor response will be assessed according to RECIST v1.1. The primary objective of the study is to determine the objective response rate, and secondary objectives include progression-free survival, overall survival, disease control rate, and safety.

Official title: A Prospective, Open-Label Clinical Study of FOLFOX-HAIC Combined With Donafenib and Pucotenlimab as First-Line Treatment for Unresectable Intrahepatic Cholangiocarcinoma

Key Details

Gender

All

Age Range

18 Years - 75 Years

Study Type

INTERVENTIONAL

Enrollment

36

Start Date

2026-02-01

Completion Date

2028-12-31

Last Updated

2026-01-20

Healthy Volunteers

No

Conditions

Intrahepatic Cholangiocarcinoma (Icc)Hepatic Arterial Infusion Chemotherapy

Interventions

PROCEDURE

hepatic arterial infusion chemotherapy (HAIC)

This intervention consists of a combination regimen including hepatic arterial infusion chemotherapy, targeted therapy, and immunotherapy for the treatment of unresectable intrahepatic cholangiocarcinoma. Hepatic arterial infusion chemotherapy is delivered through an implanted hepatic arterial catheter using a FOLFOX-based regimen, allowing high local drug concentrations within the liver while reducing systemic exposure. Donafenib, an oral multikinase inhibitor with anti-angiogenic activity, is administered continuously during treatment. Pucotenlimab, a programmed cell death protein-1 inhibitor, is administered by intravenous infusion to enhance antitumor immune responses. The combination is intended to achieve synergistic antitumor effects through regional cytotoxic chemotherapy, inhibition of tumor angiogenesis, and immune checkpoint blockade. Safety and antitumor activity of the regimen will be evaluated throughout the study period.

DRUG

Donafenib

This intervention consists of a combination regimen including hepatic arterial infusion chemotherapy, targeted therapy, and immunotherapy for the treatment of unresectable intrahepatic cholangiocarcinoma. Hepatic arterial infusion chemotherapy is delivered through an implanted hepatic arterial catheter using a FOLFOX-based regimen, allowing high local drug concentrations within the liver while reducing systemic exposure. Donafenib, an oral multikinase inhibitor with anti-angiogenic activity, is administered continuously during treatment. Pucotenlimab, a programmed cell death protein-1 inhibitor, is administered by intravenous infusion to enhance antitumor immune responses. The combination is intended to achieve synergistic antitumor effects through regional cytotoxic chemotherapy, inhibition of tumor angiogenesis, and immune checkpoint blockade. Safety and antitumor activity of the regimen will be evaluated throughout the study period.

DRUG

Pucotenlimab

This intervention consists of a combination regimen including hepatic arterial infusion chemotherapy, targeted therapy, and immunotherapy for the treatment of unresectable intrahepatic cholangiocarcinoma. Hepatic arterial infusion chemotherapy is delivered through an implanted hepatic arterial catheter using a FOLFOX-based regimen, allowing high local drug concentrations within the liver while reducing systemic exposure. Donafenib, an oral multikinase inhibitor with anti-angiogenic activity, is administered continuously during treatment. Pucotenlimab, a programmed cell death protein-1 inhibitor, is administered by intravenous infusion to enhance antitumor immune responses. The combination is intended to achieve synergistic antitumor effects through regional cytotoxic chemotherapy, inhibition of tumor angiogenesis, and immune checkpoint blockade. Safety and antitumor activity of the regimen will be evaluated throughout the study period.

DRUG

FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin)

This intervention consists of a combination regimen including hepatic arterial infusion chemotherapy, targeted therapy, and immunotherapy for the treatment of unresectable intrahepatic cholangiocarcinoma. Hepatic arterial infusion chemotherapy is delivered through an implanted hepatic arterial catheter using a FOLFOX-based regimen, allowing high local drug concentrations within the liver while reducing systemic exposure. Donafenib, an oral multikinase inhibitor with anti-angiogenic activity, is administered continuously during treatment. Pucotenlimab, a programmed cell death protein-1 inhibitor, is administered by intravenous infusion to enhance antitumor immune responses. The combination is intended to achieve synergistic antitumor effects through regional cytotoxic chemotherapy, inhibition of tumor angiogenesis, and immune checkpoint blockade. Safety and antitumor activity of the regimen will be evaluated throughout the study period.

Inclusion Criteria: * Male or female participants aged 18 to 75 years. * Histologically or clinically diagnosed Hepatocellular Carcinoma (HCC) according to AASLD or EASL guidelines. * Disease stage classified as Barcelona Clinic Liver Cancer (BCLC) stage B (unresectable) or stage C. * No prior systemic treatment for advanced HCC (treatment-naïve). * At least one measurable lesion according to RECIST v1.1 criteria. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Child-Pugh liver function class A (score 5-6). * Life expectancy of at least 3 months. * Adequate bone marrow function: Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L, Platelets ≥ 75 × 10\^9/L, and Hemoglobin ≥ 90 g/L. * Adequate liver function: Total bilirubin ≤ 1.5 × ULN; ALT and AST ≤ 5 × ULN. * Adequate renal function: Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL/min. * Adequate coagulation function: INR ≤ 1.5 or PT ≤ 1.5 × ULN. * Participants suitable for hepatic artery catheterization and HAIC treatment as assessed by the investigator. * Willingness to provide written informed consent. Exclusion Criteria: * Known hypersensitivity or allergy to Oxaliplatin, Fluorouracil, Leucovorin, Donafenib, Pucotenlimab, or any of their excipients. * Previous treatment with anti-PD-1/PD-L1 antibodies, anti-CTLA-4 antibodies, or other immunomodulatory agents. * Diagnosis of other malignant tumors within the past 5 years (excluding cured basal cell carcinoma of the skin or carcinoma in situ of the cervix). * Presence of central nervous system (CNS) metastases. * Active, known, or suspected autoimmune disease (e.g., systemic lupus erythematosus, rheumatoid arthritis) requiring systemic treatment. * History of gastrointestinal bleeding, esophageal or gastric varices with bleeding risk, or other active bleeding within 6 months prior to enrollment. * Severe cardiovascular disease, including unstable angina, myocardial infarction within 6 months, or uncontrolled hypertension. * Active infection requiring systemic antibiotic therapy. * Hepatitis B virus (HBV) DNA \> 2000 IU/mL (participants must receive antiviral treatment to suppress viral load). * Known Human Immunodeficiency Virus (HIV) infection or active Syphilis infection. * Anatomy unsuitable for hepatic arterial catheterization (e.g., severe vascular variation or occlusion). * Pregnant or breastfeeding women. * Any condition that, in the opinion of the investigator, would jeopardize the safety of the participant or the integrity of the study data.

Locations (1)

Sun Yat-san University Cancer Center

Guangzhou, Guangdong, China

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