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

NCT07353827 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: B2025-688-01
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Intrahepatic Cholangiocarcinoma (Icc); Hepatic Arterial Infusion Chemotherapy

Keywords

Unresectable liver cancer; Hepatic arterial infusion chemotherapy; Oxaliplatin-based chemotherapy; Immune checkpoint inhibitor therapy; Targeted anti-angiogenic therapy; Phase II clinical trial

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  The ORR is defined as the percentage of participants who achieve a confirmed Complete Response (CR) or Partial Response (PR). Efficacy will be evaluated by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

  From baseline until disease progression or loss of clinical benefit, assessed approximately every 6 to 9 weeks, up to 2 years.

Secondary Outcomes (6)

• Progression-Free Survival (PFS)

  From baseline up to approximately 2 years.

• Overall Survival (OS)

  From baseline up to approximately 3 years.

• Disease Control Rate (DCR)

  From baseline until disease progression, assessed approximately every 6 to 9 weeks, up to 2 years.

• Duration of Response (DoR)

  From date of first response up to approximately 2 years.

• Safety (Adverse Events)

  From the first dose of study treatment through 30 days after the last dose.

Study Arms (1)

FOLFOX-HAIC + Donafenib + Pucotenlimab

EXPERIMENTAL

Participants receive combination therapy in 21-day cycles: HAIC (FOLFOX): Hepatic Arterial Infusion Chemotherapy administered on Day 1 via a port-catheter system: Oxaliplatin: 85 mg/m\^2 intra-arterial infusion (2 hours). Leucovorin: 400 mg/m\^2 intra-arterial infusion (2 hours). Fluorouracil: 400 mg/m\^2 bolus intra-arterial injection, followed by 2400 mg/m\^2 continuous intra-arterial infusion over 46 hours. Pucotenlimab: 200 mg administered via intravenous (IV) infusion on Day 1. Donafenib: 0.2 g (200 mg) administered orally, twice daily (BID), continuously throughout the cycle. Treatment continues until disease progression, unacceptable toxicity, or withdrawal of consent.

Procedure: hepatic arterial infusion chemotherapy (HAIC); Drug: Donafenib; Drug: Pucotenlimab; Drug: FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin)

Interventions

hepatic arterial infusion chemotherapy (HAIC) PROCEDURE

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.

FOLFOX-HAIC + Donafenib + Pucotenlimab

Donafenib DRUG

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.

FOLFOX-HAIC + Donafenib + Pucotenlimab

Pucotenlimab DRUG

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.

FOLFOX-HAIC + Donafenib + Pucotenlimab

FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin) DRUG

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.

FOLFOX-HAIC + Donafenib + Pucotenlimab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-san University Cancer Center

Guangzhou, Guangdong, 510080, China

Location

MeSH Terms

Conditions

Cholangiocarcinoma; Cirrhosis, Familial, with Pulmonary Hypertension

Interventions

donafenib; Folfox protocol; Fluorouracil; Leucovorin; Oxaliplatin

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals

Central Study Contacts

Zhongguo Zhou, PhD

CONTACT

020-87343115; zhouzhg@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 4, 2026
• First Posted: January 20, 2026
• Study Start: February 1, 2026
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: January 20, 2026

Record last verified: 2026-01

Locations

CN (1)