The DoHAICs Study Expansion Phase

Clinical Study on the Efficacy and Safety of Donafenib Combined With Hepatic Artery Infusion Chemotherapy and Sintilimab as the First-line Treatment for Unresectable Hepatocellular Carcinoma - the DoHAICs Study Expansion Phase

We explored the efficacy and safety of the first-line treatment of unresectable hepatocellular carcinoma with donafenib combined with hepatic artery infusion chemotherapy (HAIC) and sintilimab .

Study Overview

• Status: Not yet recruiting
• Conditions: HCC - Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Donafenib; Drug: sintilimab; Procedure: HAIC

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Voluntarily participate in the trial and provide written informed consent.
• Age between 18 and 80 years (inclusive), regardless of gender.
• Patients with hepatocellular carcinoma (HCC) clinically diagnosed per the "Standard for Diagnosis and Treatment of Primary Liver Cancer (2024 Edition)" or confirmed by histology/cytology.
• Patients with inoperable or metastatic hepatocellular carcinoma.
• No prior systemic therapy for advanced disease. Patients who received adjuvant chemotherapy following local therapy are eligible if chemotherapy was completed >12 months ago and disease progression or metastasis has occurred.
• Completion of the last interventional therapy, radiotherapy, or ablation therapy >4 weeks prior.
• For patients with prior hepatectomy, resection must have been R0, and tumor recurrence must have occurred more than 24 months after surgery.
• At least one measurable lesion as defined by RECIST 1.1 criteria.
• Life expectancy ≥3 months.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Child-Pugh score ≤7.
• Able and willing to comply with the protocol for the observation of adverse events and efficacy.
• Adequate organ function, defined as meeting the following criteria:
• Hematological function (without transfusion or granulocyte colony-stimulating factor [G-CSF] support within 14 days prior to screening):
• Hemoglobin ≥90 g/L.
• Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L.
• Platelet count ≥75 × 10⁹/L.
• Biochemical tests (without albumin infusion within 14 days prior to screening):
• Albumin ≥28 g/L.
• Total bilirubin ≤2 × upper limit of normal (ULN).
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤5 × ULN.
• Alkaline phosphatase (ALP) ≤5 × ULN.
• Serum creatinine ≤1.5 × ULN.
• Coagulation function:
• International normalized ratio (INR) or prothrombin time (PT) ≤1.5 × ULN.
• Activated partial thromboplastin time (APTT) ≤1.5 × ULN.

Exclusion Criteria:

• Histologically/cytologically confirmed components such as fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, or cholangiocarcinoma.
• History of malignancies other than hepatocellular carcinoma, except under the following circumstances:
• The patient has undergone potentially curative treatment with no evidence of that disease for 5 years.
• Successfully resected basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the cervix, or other carcinoma in situ.
• Diffuse tumor lesions.
• History of hepatic encephalopathy, hepatorenal syndrome, or liver transplantation.
• Clinically symptomatic pleural effusion, ascites, or pericardial effusion requiring drainage.
• Central nervous system metastases.
• History of severe psychiatric illness.
• Diseases affecting the absorption, distribution, metabolism, or excretion of the investigational drug (e.g., severe vomiting, chronic diarrhea, intestinal obstruction, malabsorption, etc.).
• Prior allogeneic stem cell or solid organ transplantation.
• Prior treatment with anti-VEGF/VEGFR, RAF, MEK pathway targeted therapies (e.g., sorafenib, lenvatinib, regorafenib) or immunomodulators (e.g., anti-PD-1, anti-PD-L1, anti-CTLA-4 antibodies).
• Prior other systemic anti-tumor therapy, including Chinese herbal medicine with anti-tumor indications, completed less than 2 weeks before study drug initiation; or patients with adverse events from prior therapy not recovered to ≤ Grade 1 per CTCAE (excluding alopecia and Grade 1/2 neuropathy caused by oxaliplatin).
• Concurrent use of medications known to prolong QTc interval and/or induce Torsades de Pointes (TdP), or medications that affect drug metabolism.
• Past or present congenital or acquired immunodeficiency diseases.
• Active or history of autoimmune or inflammatory diseases (including but not limited to: autoimmune hepatitis, interstitial pneumonia, inflammatory bowel disease, systemic lupus erythematosus, vasculitis, uveitis, hypophysitis, hyper- or hypothyroidism, asthma requiring bronchodilators, etc.). Patients with vitiligo or asthma that was fully resolved in childhood and requires no intervention in adulthood may be included.
• Use of systemic immunosuppressive medication within 2 weeks prior to enrollment, or anticipated requirement for such medication during the study, except for:
• Intranasal, inhaled, topical, or local corticosteroid injections (e.g., intra-articular).
• Systemic corticosteroids at physiological doses not exceeding 10 mg/day prednisone or equivalent.
• Prophylactic use of corticosteroids for hypersensitivity reactions.
• Known or suspected hypersensitivity to donafenib, drugs of the same class, or history of hypersensitivity to chimeric or humanized antibodies or fusion proteins, or allergy to any excipient of the investigational drug.
• Active bleeding or coagulation disorders, bleeding tendency, or undergoing thrombolytic, anticoagulant, or antiplatelet therapy.
• Thrombotic or thromboembolic events within the past 6 months, such as stroke and/or transient ischemic attack, deep vein thrombosis, pulmonary embolism, etc.
• History of esophageal or gastric variceal bleeding due to portal hypertension within the past 6 months, or any life-threatening bleeding event within the past 3 months.
• Significant cardiovascular disease, including but not limited to: acute myocardial infarction, severe/unstable angina, or coronary artery bypass grafting within the past 6 months; congestive heart failure (NYHA class >2); poorly controlled arrhythmias requiring pacemaker treatment; uncontrolled hypertension (systolic BP ≥140 mmHg and/or diastolic BP ≥90 mmHg).
• Other clinically significant abnormalities, deemed by the investigator to affect safety evaluation, such as uncontrolled diabetes, chronic kidney disease, Grade II or higher peripheral neuropathy (CTCAE v6.0), abnormal thyroid function, etc.
• Active or poorly controlled severe infection; active infections including:
• Positive for Human Immunodeficiency Virus (HIV) (HIV1/2 antibodies).
• Active Hepatitis B (HBsAg positive or HBV DNA >2000 IU/mL with abnormal liver function).
• Active Hepatitis C (HCV antibody positive or HCV RNA ≥10³ copies/mL with abnormal liver function).
• Active tuberculosis.
• Other uncontrolled active infections (CTCAE v6.0 > Grade 2).
• Incomplete recovery from surgery, such as unhealed wounds or severe postoperative complications.
• Pregnancy, lactation, or patients of childbearing potential unwilling or unable to use effective contraception.

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: Donafenib combined with hepatic artery infusion chemotherapy and sintilimab; Donafenib combined with hepatic artery infusion chemotherapy and sintilimab injection as the first-line treatment for unresectable hepatocellular carcinoma

Drug: Donafenib; Donafenib (200 mg twice daily, taken orally, initiated 3-7 days before the first HAIC session); Drug: sintilimab; sintilimab (200 mg intravenously every 3 weeks, administered 0-1 day before each HAIC treatment); Procedure: HAIC; HAIC (oxaliplatin 85 mg/m2 over 2 hours, leucovorin 400 mg/m2 over 2 hours, bolus fluorouracil 400 mg/m2 within the first 10 minutes, followed by fluorouracil infusion 1200 mg/m2 over 23 hours, every 3 weeks.)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
event-free survival	The time from enrollment to the date of first documented progression, recurrence, or death from any cause, whichever came first, assessed up to 36 months

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): May 20, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: December 22, 2025
• First Submitted That Met QC Criteria: May 7, 2026
• First Posted (Actual): May 13, 2026

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Surgical resection; Hepatic artery infusion chemotherapy; Hepatocellular carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; sintilimab; donafenib
• Other Study ID Numbers: E20251318

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No