Combining therapies for advanced liver cancer that can't be surgically removed

Combined Hepatic Arterial Infusion Chemotherapy, Tyrosine Kinase Inhibitor/ Anti-VEGF Antibody, and Anti-PD-1/ PD-L1 Antibody as Conversion Therapy for Unresectable Hepatocellular Carcinoma

This study is testing a new combination of treatments for patients with advanced liver cancer that can't be surgically removed to see if it helps them live longer and feel better than standard options.

Quick facts

• Study type: Observational
• Enrollment: 300 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Tongji Hospital (Academic / other)
• Drugs / interventions: prednisone, chemotherapy
• Locations: 2 sites (Quanzhou, Fujian and 1 other locations)
• Trial ID: NCT05713994 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness and safety of a combination therapy involving hepatic artery infusion chemotherapy (HAIC), tyrosine kinase inhibitors (TKIs), anti-VEGF antibodies, and immune checkpoint inhibitors (ICIs) for patients with unresectable hepatocellular carcinoma (HCC). The approach aims to improve tumor response rates and survival outcomes compared to traditional treatments. The study will enroll approximately 300 patients across four research centers, collecting data from routine blood tests, imaging, and pathology to predict therapeutic effects and clinical prognosis. The enrollment is expected to be completed within one year, with a follow-up period of three years for all participants.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with unresectable hepatocellular carcinoma who have measurable lesions and a performance status score of 0 or 1.

Not a fit: Patients with resectable hepatocellular carcinoma or those with severe comorbidities that affect treatment tolerance may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could significantly improve treatment outcomes for patients with advanced liver cancer that cannot be surgically removed.

How similar studies have performed: Previous studies have shown promising results with similar combination therapies in treating advanced hepatocellular carcinoma, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 18 years old;
2. Diagnosis of HCC is according to the American Association for the Study of Liver Diseases or European Association for the Study of the Liver guidelines of HCC management;
3. at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or mRESIST criteria;
4. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1;
5. Hepatocellular carcinoma (HCC) was assessed as not suitable for radical resection, liver transplant, or ablation treatment after the assessment of a multidisciplinary team because either: (1) R0 resection was not feasible; (2) remnant liver volume was less than 30% in patients who did not have cirrhosis or 40% in patients with cirrhosis, or the results of an indocyanine green test were higher than 15%; (3) patients had Barcelona Clinic Liver Cancer (BCLC) stage B and beyond Up-to-seven criteria; or (4) patients had BCLC stage C.
6. Portal vein involvement (Chen's groups A and B, or Cheng's type I-III) is allowed: Chen's group A1 or Cheng's type I, tumor thrombus is involved in segmental or sectoral branches of the portal vein or above; Chen's group A2 or Cheng's type II, involvement of the first branch of portal vein; Chen's group B or Cheng's type III, involvement of the main portal vein.
7. Hepatic vein invasion (VV1 to VV2) were allowed. Patients with tumor thrombus in inferior vena cava (VV3 type, Sakamoto type 1) can be included; However, patients with inferior vena cava tumor thrombus exceeding the diaphragmatic plane (Sakamoto type II) and reaching the right atrium (Sakamoto type III) cannot be included in the study;
8. Patients with extrahepatic oligometastasis is allowed: extrahepatic oligometastasis was defined as up to three metastatic lesions in up to two organs with the largest diameter of 3 cm
9. Child-Pugh liver function class A-B7
10. No prior transplantation, TACE, or radioembolization to the liver was allowed. Prior locoregional therapies, such as surgical resection, radiotherapy, radiofrequency ablation, percutaneous ethanol injection or cryoablation, are allowed if the disease have progressed since prior treatment. Local therapy must have been completed at least 4 weeks prior to the baseline scan.
11. Adequate organ and marrow function, as defined below:

(1) Hemoglobin≥80 g/L; (2) Absolute neutrophil count ≥1.5 ×10\^9/L; (3) Platelet count ≥50 ×10\^9/L; (4) Total bilirubin \< 51 μmol/L; (5) Alanine transaminase (ALT) and aminotransferase (AST)≤5×ULN; (6) Albumin ≥28 g/L; (7) INR ≤1.6; (8) Serum creatinine \< 110 μmol/L.

Exclusion Criteria:

1. Prior invasive malignancy within 2 years except for noninvasive malignancies such as cervical carcinoma in situ, in situ prostate cancer, non-melanomatous carcinoma of the skin, lobular or ductal carcinoma in situ of the breast that has been surgically cured
2. Severe, active and uncontrolled co-morbidity including but not limited to:

(1) Persistent or activity (except the HBV and HCV) infection; (2) symptoms of congestive heart failure and uncontrolled diabetes; (3) uncontrolled hypertension, systolic pressure≥160 mmHg or diastolic pressure≥100 mmHg despite anti-hypertension medications≤28 days before randomization or first dose of drug; (4) unstable angina; (5) uncontrolled arrhythmias; (6) active ILD; (7) severe chronic GI disease accompanied by diarrhea; (8) compliance with requirements may limit the research, resulted in significant increase risk of AE or influence Subjects provided psychiatric/social problem status on their ability to provide written informed consent; (9) A history of active primary immunodeficiency or human immunodeficiency virus; (10) Active or previous records of autoimmune disease or inflammatory diseases, including inflammatory bowel disease (e.g., colitis or Crohn's disease\], diverticulitis, except \[diverticulosis\], systemic lupus erythematosus (SLE), sarcoidosis syndrome or Wegener syndrome (e.g., granulomatous vasculitis, gray's disease, rheumatoid arthritis, the pituitary gland inflammation and uveitis\]); (11) A history of hepatic decompensation, including refractory ascites, gastrointestinal bleeding, or hepatic encephalopathy.

3\. Known to produce allergic or hypersensitive reactions to any study drug or any excipient thereof.

4\. Significant clinical gastrointestinal bleeding or a potential risk of bleeding was identified by the investigator during the 30 days prior to study entry.

5\. Tumors of the central nervous system, including metastatic brain tumors. 6. Pregnant women or breast-feeding patients. 7. Has received anti-tumor system therapy for HCC. Non-anti-tumor purpose combined hormone therapy (e.g., hormone replacement therapy) is excluded.

8\. Is currently using, or has used an immunosuppressive drug within 14 days prior to the first dose of the investigational drug. This standard has the following exceptions: (1) intranasal, inhaled, topical or topical steroids. (e.g., intraarticular); (2) Systemic corticosteroid therapy not exceeding 10 mg/ day of prednisone; (3) prophylactic use of steroids for hypersensitivity. (e.g., CT scan pretherapy medication).

9\. A live attenuated vaccine was administered within 30 days prior to the first administration of the study drug. Note: If enrolled, patients shall not receive live attenuated vaccine within 30 days of receiving study drug therapy and after the last administration of study drug.

10\. Extrahepatic vascular involvement or thrombosis: superior mesenteric vein (Cheng's type IV), or with inferior vena cava tumor thrombus exceeding the diaphragmatic plane (Sakamoto type II) or reaching the right atrium (Sakamoto type III) cannot be included in the study.

Where this trial is running

Quanzhou, Fujian and 1 other locations

• The Second Affiliated Hospital of Fujian Medical University — Quanzhou, Fujian, China (Recruiting)
• TongjiHospital — Wuhan, Hubei, China (Recruiting)

Study contacts

• Study coordinator: ZeYang Ding, M.D.

Conditions Hepatocellular Carcinoma Non-resectable; Liver Neoplasms; Hepatocellular Carcinoma