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

Sun Yat-sen University

Status and phase: Not yet enrolling; Phase 2

Conditions: Hepatic Arterial Infusion Chemotherapy; Intrahepatic Cholangiocarcinoma (Icc)

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

Study type: Interventional

Funder types: Other

Identifiers

NCT07353827

B2025-688-01

Details and patient eligibility

About

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.

Enrollment: 36 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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36 participants in 1 patient group

FOLFOX-HAIC + Donafenib + Pucotenlimab

Experimental group

Description:

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.

Treatment:

Drug: Donafenib

Drug: FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin)

Procedure: hepatic arterial infusion chemotherapy (HAIC)

Drug: Pucotenlimab