Combination treatment for advanced liver cancer

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 study is testing a new combination of treatments for people with advanced liver cancer to see if it helps them live longer and feel better.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 38 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (Academic / other)
• Drugs / interventions: prednisone, Sintilimab
• Locations: 1 site (Wuhan, Hubei)
• Trial ID: NCT06244225 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of hepatic artery infusion chemotherapy (HAIC) combined with Sintilimab and Donafenib for patients with unresectable hepatocellular carcinoma at BCLC stage C. It is a single-arm, non-randomized study that aims to include 38 participants who have not received prior systemic therapy. The trial will assess treatment outcomes such as progression-free survival and overall survival over the course of the study.

Who should consider this trial

Good fit: Ideal candidates are patients with newly diagnosed unresectable hepatocellular carcinoma at BCLC stage C who have not undergone any previous treatment.

Not a fit: Patients with specific types of liver cancer, such as fibrolamellar or cholangiocarcinoma, or those with significant liver dysfunction may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment approach could provide a new first-line therapy option for patients with advanced liver cancer.

How similar studies have performed: While this approach is innovative, similar studies have shown promise in combining targeted therapies with chemotherapy for liver cancer treatment.

Eligibility criteria

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.

Where this trial is running

Wuhan, Hubei

• Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology — Wuhan, Hubei, China (Recruiting)

Conditions Hepatocellular Carcinoma