HAIC (Hepatic Artery Infusion Chemotherapy，HAIC）Plus Sintilimab and Donafenib in the First-line Treatment of Unresectable Hepatocellular Carcinoma

NCT06244225 | Recruiting Phase 2

• 1 other identifier: UHCT230851
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-arm exploratory clinical study to evaluate the efficacy and safety of HAIC in combination with Sintilimab and Donafenib in patients with BCLC-C stage who have not received prior systemic therapy

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS) per RECIST v1.1

  Defined as a duration from the date of initial treatment to disease progression or death of any cause

  From baseline to primary completion date, about 18 months

Secondary Outcomes (5)

• Overall response rate (ORR) per RECIST v1.1 and mRECIST

  From baseline to primary completion date, about 18 months

• Disease control rate (DCR) per RECIST v1.1 and mRECIST

  From baseline to primary completion date, about 18 months

• Overall survival (OS)

  From baseline to primary completion date, about 18 months

• Duration of response (DoR) per RECIST v1.1 and mRECIST

  From baseline to primary completion date, about 18 months

• The treatment-related adverse events (TRAEs）

  From baseline to primary completion date, about 18 months

Study Arms (1)

HAIC + Sintilimab + Donafenib

EXPERIMENTAL

HAIC combine with Sintilimab and Donafenib

Drug: Donafenib； Sintilimab； HAIC

Interventions

Donafenib； Sintilimab； HAIC DRUG

Drug: Sintilimab Q3W 200mg IV d1, Q3W Drug: Donafenib 200 mg BID d1-21, Q3W other: HAIC Q3W Oxaliplatin: 85mg/m2 , Day 1 Leucovorin: 200mg/m2, Day 1 Fluorouracil: 400mg/m2, Day1 and 2400mg/m2 continuous arterial perfusion for 46h.

HAIC + Sintilimab + Donafenib

Eligibility Criteria

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

You may qualify if:

• Written informed consent should be signed before implementing any trial-related procedures
• ECOG PS scores 0-1
• Histologically/cytologically confirmed HCC or cirrhosis meeting the clinical diagnostic criteria of HCC by American Association for the Study of Liver Diseases (AASLD)
• Barcelona Clinic Liver Cancer (BCLC) stage C
• Newly diagnosed HHC patients without any previous treatment for the tumor
• Child Pugh score of ≤ 7.
• Estimated survival \> 12 weeks
• At least one measurable lesion according to RECIST V1.1
• Sufficient organ and bone marrow functions

You may not qualify if:

• Histologically/cytologically confirmed fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, and cholangiocarcinoma.
• History of hepatic encephalopathy or liver transplantation.
• Symptomatic pleural effusion, ascites, and pericardial effusion that require drainage.
• Acute or chronic active hepatitis B or C infection; hepatitis B virus (HBV) DNA \> 2000 IU/mL or 104 copies/mL; hepatitis C virus (HCV) RNA \> 103 copies/mL; hepatitis B surface antigen (HbsAg) and anti HCV antibody positive concurrently.
• Presence of metastasis to the central nervous system.
• Presence of bleeding events from esophageal or gastric varices caused by portal hypertension within the past 6 months. Presence of known severe (G3) varicose veins in endoscopy within 3 months before the first dose. Evidence of portal hypertension (including the finding of splenomegaly in imaging studies) with a high risk of bleeding assessed by the investigator.
• Presence of any life-threatening bleeding events within the past 3 months, including the need for transfusion, surgery or local treatment, and continuous medication therapy.
• Any arterial/venous thromboembolic events within 6 months, including myocardial infarction, unstable angina, cerebrovascular accident or transient cerebral ischemic attack, pulmonary embolism, deep vein thrombosis, or any other history of serious thromboembolism. Presence of implantable venous port or catheter derived thrombosis, or superficial venous thrombosis, barring stable thrombosis following the conventional anticoagulation treatment. Prophylactic use of low dose low molecular weight heparin (e.g., enoxaparin 40 mg/day) is permitted.
• Involvement of both the main portal vein and the left and right branches by portal vein tumor thrombus, or of both the main trunk and the superior mesenteric vein concurrently. Presence of tumor thrombus of inferior vena cava.
• A 10-day consecutive dosing of aspirin (\> 325 mg/day) or other drugs, e.g., dipyridamole and clopidogrel, known to inhibit the platelet function within 2 weeks before the first dose.
• Uncontrolled hypertension (systolic greater than 140 mmHg or diastolic greater than 90 mmHg) after the optimal medical treatment, history of hypertensive crisis or hypertensive encephalopathy.
• Toxicity (excluding alopecia, events not clinically significant, and asymptomatic laboratory abnormalities) caused by previous therapy that has not yet resolved to grade 0 or 1 (National Cancer Institute Common Terminology Criteria for Adverse Events V5.0 (NCI CTCAE V5.0)) before the first dose of study drugs.
• Symptomatic congestive cardiac failure (NYHA Class II IV). Symptomatic or poorly controlled arrhythmia. History of congenital long QT syndrome or corrected QTc \> 500 ms (calculated using Fridericia formula) during screening.
• Serious hemorrhagic tendency or coagulopathy, or currently receiving thrombolytic therapy.
• History of gastrointestinal perforation and/or fistula, history of bowel obstruction (including incomplete bowel obstruction requiring parenteral nutrition), extensive bowel resection (partial colectomy or extensive small bowel resection accompanied with chronic diarrhea), Crohn's disease, ulcerative colitis, or chronic diarrhea within the past 6 months.

Sponsors & Collaborators

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: lead

Study Sites (1)

Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology

Wuhan, Hubei, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2024
• First Posted: February 6, 2024
• Study Start: January 1, 2024
• Primary Completion: January 1, 2026
• Study Completion (Estimated): January 1, 2028
• Last Updated: February 6, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)