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

Official title

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

Overview

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.

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
• 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
• 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
• 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

Primary outcome measures

• Objective Response Rate (ORR) [Time frame: From baseline until disease progression or loss of clinical benefit, assessed approximately every 6 to 9 weeks, up to 2 years.]

Secondary outcome measures (6)

• Progression-Free Survival (PFS) [Time frame: From baseline up to approximately 2 years.]
• Overall Survival (OS) [Time frame: From baseline up to approximately 3 years.]
• Disease Control Rate (DCR) [Time frame: From baseline until disease progression, assessed approximately every 6 to 9 weeks, up to 2 years.]
• Duration of Response (DoR) [Time frame: From date of first response up to approximately 2 years.]
• Safety (Adverse Events) [Time frame: From the first dose of study treatment through 30 days after the last dose.]
• Surgical Conversion Rate [Time frame: From baseline up to approximately 2 years.]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Sun Yat-san University Cancer Center — Guangzhou

Identifiers

NCT: NCT07353827 · B2025-688-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗