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

An Exploratory Study to Evaluate the Efficacy and Safety of Hepatic Arterial Infusion Chemotherapy (HAIC) Combine With Sintilimab and Donafenib for Unresectable Hepatocellular Carcinoma

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

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Donafenib； Sintilimab； HAIC

Detailed Description

This trial is a single-arm, non-randomized and single-center clinical study of HAIC in combination with Sintilimab and Donafenib in the first-line treatment of BCLC-C stage unresectable hepatocellular carcinoma. The study is expected to include 38 subjects who meet the screening criteria to receive HAIC plus Sintilimab and Donafenib to evaluate the efficacy and safety of treatment, including time to progression（PFS）and overall survival（OS），etc.

• Study Type: Interventional
• Enrollment (Estimated): 38
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China
      • Recruiting
      • Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology
      • Contact: Bin Liang; Phone Number: 86-18086006235; Email: 553954881@qq.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

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

Exclusion Criteria:

1. Histologically/cytologically confirmed fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, and cholangiocarcinoma.
2. History of hepatic encephalopathy or liver transplantation.
3. Symptomatic pleural effusion, ascites, and pericardial effusion that require drainage.
4. 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.
5. Presence of metastasis to the central nervous system.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. Serious hemorrhagic tendency or coagulopathy, or currently receiving thrombolytic therapy.
15. 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.
16. Receipt of immunosuppressants within 4 weeks before the first dose, excluding local glucocorticoids administered by nasal, inhaled, or other topical routes, or systemic glucocorticoids of physiological doses (no more than 10 mg/day of prednisone or equivalents), while the temporary use of glucocorticoids for preventing allergies or treating dyspneic symptoms of such diseases as asthma and chronic obstructive pulmonary disease is permitted.
17. Receipt of a live attenuated vaccine within 4 weeks before the first dose or planned to receive a live attenuated vaccine during the study.
18. Receipt of major surgery (craniotomy, thoracotomy, or laparotomy) within 4 weeks before the first dose or having unhealed wounds, ulcers, or fractures. Receipt of tissue biopsy or other minor surgeries within 7 days before the first dose, barring venipuncture and catheterization for intravenous infusion.

19. Receipt of local treatment for liver cancer within 4 weeks before the first dose.

    Receipt of systemic treatment with traditional Chinese medicines with cancer indications or immunomodulators (including thymosin, interferon, and interleukin, barring local use for controlling pleural fluid or ascites) within 2 weeks before the first dose.

20. Uncontrolled/uncorrectable metabolic disorders, other non malignant organ diseases, systemic diseases, or cancer related secondary diseases with the potential to cause a relatively high medical risk and/or survival evaluation uncertainties unsuitable for subject enrollment as judged by the investigator; other circumstances unsuitable for subject enrollment as judged by the investigator.

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: HAIC + Sintilimab + Donafenib; HAIC combine with Sintilimab and Donafenib	Drug: Donafenib； Sintilimab； HAIC; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR) per RECIST v1.1 and mRECIST	Defined as the incidence of complete response and, partial response	From baseline to primary completion date, about 18 months
Disease control rate (DCR) per RECIST v1.1 and mRECIST	Defined as the incidence of complete response, partial response and stable disease	From baseline to primary completion date, about 18 months
Duration of response (DoR) per RECIST v1.1 and mRECIST	Defined as a duration from date of initial treatment to disease progression or death in patients who achieve complete or partial response	From baseline to primary completion date, about 18 months
Overall survival (OS)	Defined as a duration from the date of initial treatment to death of any cause.	From baseline to primary completion date, about 18 months
The treatment-related adverse events (TRAEs）	Defined as the proportion of patients with AE, treatment-related AE (TRAE), immune-related AE (irAE), serious adverse event (SAE), assessed by NCI CTCAE v5.0	From baseline to primary completion date, about 18 months

Collaborators and Investigators

• Sponsor: Wuhan Union Hospital, China

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: January 29, 2024
• First Submitted That Met QC Criteria: January 29, 2024
• First Posted (Estimated): February 6, 2024

Study Record Updates

• Last Update Posted (Estimated): February 6, 2024
• Last Update Submitted That Met QC Criteria: January 29, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: UHCT230851

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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