Combining chemotherapy with Lenvatinib and PD-1 inhibitors for advanced liver cancer with blood vessel blockage

Hepatic Arterial Infusion Chemotherapy Combine With Lenvatinib and PD-1 Inhibitors for Advanced Hepatocellular Carcinoma With Portal Vein Tumor Thrombosis.

This study is testing whether combining a specific chemotherapy with Lenvatinib and PD-1 inhibitors can help people with advanced liver cancer and blood vessel blockage live longer and feel better compared to just using Lenvatinib and PD-1 inhibitors alone.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 66 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Peking University (Academic / other)
• Drugs / interventions: Lenvatinib, chemotherapy
• Locations: 1 site (Beijing, Beijing)
• Trial ID: NCT05166239 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and efficacy of hepatic arterial infusion chemotherapy (HAIC) combined with Lenvatinib and PD-1 inhibitors in patients with advanced hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT). The trial aims to compare this combination treatment to Lenvatinib plus PD-1 inhibitors alone. A total of 66 subjects will be recruited, with 33 in each treatment group. The primary endpoint is the six-month progression-free survival rate, while secondary endpoints include overall survival and other efficacy measures.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with advanced HCC and confirmed PVTT who have not undergone systemic chemotherapy or HAIC.

Not a fit: Patients with distant metastasis or those with severe liver dysfunction may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve survival rates for patients with advanced liver cancer and portal vein thrombosis.

How similar studies have performed: Previous studies have shown promising results for HAIC in liver cancer, suggesting potential success for this combined approach.

Eligibility criteria

Inclusion Criteria:

1. Age and gender: \>18 years old and≤75 years old, both men and women.
2. All subjects must have advanced hepatocellular carcinoma with portal vein tumor thrombosis confirmed by pathological or clinical diagnosis.
3. One measurable lesion at least.
4. ECOG PS 0-1 before 1 week of treatment begnining.
5. Child-Pugh class A; ALBI class 1-2.
6. Systemic-cheomtherapy-naive and HAIC-naive.
7. BCLC C stage with PVTT (Vp1 - Vp4).
8. Without distant metastasis.
9. Patients who are expected to live more than 3 months.
10. Subjects must volunteer to participate in the study, signed informed consent, and were able to comply with the program requirements of visits and related procedures.
11. Patients with laboratory values that meet the following criteria:

    1. Hemoglobin≥90 g/L;
    2. Neutrophile granulocytes≥1.5×109/L;
    3. Platelet count≥75×109/L;
    4. Albumin≥30 g/L;
    5. Total serum bilirubin ≤ 2 times upper limits of normal;
    6. AST and ALT ≤ 5 times upper limits of normal;
    7. Serum creatinine ≤ 1.5 times upper limits of normal;
    8. Alkaline phosphatase ≤ 5 times upper limits of normal;
    9. Prothrombin time or international normalized ratio ≤ 1.5 times upper limits of normal, activated partial thromboplastin time (APTT) ≤ 1.5×ULN.

Exclusion Criteria:

1. Fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma confirmed by histology or cytology.
2. History of malignant tumor, excluding the following cases:
3. Allergic to contrast agent.
4. Allergic to oxaliplatin.
5. History of usage of immune inhibitor drug within 14 days before the injection of PD-1 inhibitors, except nasal spray and inhaled corticosteroids or physiological doses of systemic steroid hormones (no more than 10 mg/day of prednisolone or other corticosteroids with equivalent physiological doses).
6. Factors influenced oral Lenvatinib, such as inability to swallow, chronic diarrhea and intestinal obstruction, or other conditions that significantly affect the administration and absorption of the drug.
7. Allergic to Lenvatinib, PD-1 inhibitors, and other mono-colonal antibodies.
8. Vaccination with live attenuated vaccine within 4 weeks before the first dose or planned during the study period.
9. Peripheral neuropathy\> Grade 1.
10. History of active autoimmune disease or autoimmune disease.
11. History of other malignant tumor, except for radically treated basal cell, squamous cell skin cancer, or cervical carcinoma in situ.
12. History of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) .
13. Clinically significant cardiovascular disease, including, but not limited to, acute myocardial infarction, severe/unstable angina or prior coronary artery bypass surgery, congestive heart failure (NYHA \>2), poorly controlled arrhythmias or arrhythmias requiring pacemaker therapy, hypertension not controlled by medication (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg) within the past 6 months.
14. Abnormal coagulation function (INR\>1.5 or APTT\>1.5×ULN) , have bleeding tendency, or are receiving thrombolytic therapy, anticoagulation therapy or antiplatelet therapy, etc..
15. History of inherited or acquired bleeding and thrombotic tendency, such as hemophilia, coagulopathy, thrombocytopenia, hypersplenism, etc..
16. History of significant coughing up blood 2 months before entering the study, or the daily volume of hemoptysis reached 2.5 ml or more.
17. Patients at risk of gastrointestinal bleeding, including the following:

    1. There are active peptic ulcer lesions.
    2. Those who have a history of melena and hematemesis within 3 months.
    3. For fecal occult blood (+) or (+/-), it is necessary to recheck the stool routine within 1 week. Those who still (+) or (+/-) must undergo gastroscopy. If there is ulcer, bleeding disease, and the treating physician believes that there is a potential risk of bleeding.
18. History of thrombosis and/or embolism within 6 months of the start of treatment.
19. Complicated infections requiring drug intervention (such as intravenous infusion of antibiotics, antifungal or antiviral drugs) within 4 weeks before the first treatment, or unexplained fever \>38.5°C during the screening period/before the first administration.
20. Participated in any other clinical research within 4 weeks before the first treatment.
21. History of psychotropic drug abuse or drug use.
22. Other serious physical, mental illnesses or laboratory abnormalities, which may increase the risk of participating in the research or interfere with the results of the research, and those who the researcher believes are not suitable for participating in this research.

Where this trial is running

Beijing, Beijing

• Peking Univerisity Cancer Hospital — Beijing, Beijing, China (Recruiting)

Study contacts

• Study coordinator: Xiaodong Wang, MD

Conditions Hepatocellular Carcinoma; Portal Vein Thrombosis