The Safety and Efficacy of Transarterial Chemoembolization (TACE) + Lenvatinib + Programmed Cell Death Protein 1 (PD-1) Antibody of Advanced Unresectable Hepatocellular Carcinoma

• Status: Enrolling by invitation
• Trial end date: 2024-12-01
• Target enrollment: 0
• Participant gender: All

Summary

We adopted the prospective cohort study to compare the safety and efficacy of Transarterial Chemoembolization (TACE) + Lenvatinib + Programmed Cell Death Protein 1 (PD-1) Antibody in the treatment of advanced unresectable liver cancer.The purposes of our study include：1. Primary objective: To compare the safety and efficacy of TACE combined with Lenvatinib and PD-1 antibody versus TACE alone in the conversion-resection of patients with advanced unresectable hepatocellular carcinoma.2. Secondary objective: To compare the long-term outcome of TACE combined with Lenvatinib and PD-1 antibody versus TACE alone for patients with advanced unresectable hepatocellular carcinoma.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Xinrui Zhu
• Treatments: Lenvatinib

Criteria

Inclusion Criteria:

-(1) 18 years old ≤ age ≤ 70 years old, no gender limit; (2) HCC patients who are in strict compliance with the clinical diagnostic criteria of the "Guidelines for the Diagnosis and Treatment of Hepatocellular Carcinoma (2019 Edition) or confirmed by histopathology or cytology; (3) Have not received any systemic treatment for HCC in the past. (4) ECOG PS score 0-1; (5) Child-Pugh liver function rating AB; (6) Patients with BCLC stage B and C liver cancer; or stage A patients without sufficient remaining liver volume (no cirrhosis liver: SFLVR<30%; cirrhosis liver: SFLVR<40%); (7) According to the evaluation criteria for the efficacy of solid tumors (mRECIST), there is at least one imaging measurable lesion; (8) If the patient is HBsAg positive, HBV-DNA will be less than 2000 IU/ml (10000 copies/ml) during PD-1antibody treatment; (9) The function of major organs is normal, that is, it meets the following standards:

1. . Sufficient bone marrow function, defined as: Absolute neutrophil count (ANC greater than or equal to 1.5×10^9 per liter (/L); hemoglobin (Hb greater than or equal to 8.5 grams per deciliter (g/dL); platelet count greater than or equal to 75×10^9/L).

2. . Sufficient liver function, defined as: Aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alanine aminotransferase (ALT) are less than or equal to 5 ULN.

3. . Sufficient coagulation function, defined as the International Normalized Ratio (INR) less than or equal to 2.3.

4. . Sufficient renal function is defined as a creatinine clearance rate greater than 40 milliliters per minute (mL/min), calculated according to Cockcroft and Gault formulas.

5. . Sufficient pancreatic function, defined as amylase and lipase≤1.5×ULN.

6. . Normal thyroid function is defined as thyroid stimulating hormone (TSH) within the normal range. If the baseline TSH is outside the normal range, subjects whose total T3 (or FT3) and FT4 are within the normal range can also be included in the group; (10) Use up to 3 antihypertensive drugs to adequately control blood pressure (BP), defined as BP <= 150/90 mmHg at the time of screening, and there is no change in antihypertensive treatment within 1 week before cycle 1/day 1. .

(11) The patient is expected to survive more than 3 months. (12) No pregnancy or pregnancy plans. (13) The subjects voluntarily joined the study and signed an informed consent form, with good compliance and cooperation with follow-up.

Exclusion Criteria:

• (1) Extrahepatic metastasis of primary liver cancer; (2) Diffuse liver cancer, intrahepatic tumor burden ≥50%; portal vein tumor thrombus (superior mesenteric vein tumor thrombus, type IV), inferior vena cava tumor thrombus; (3) Contraindications of TACE and epirubicin; (4) Those who have participated in other clinical trial drugs within 4 weeks; (5) Those who are known to be allergic to the ingredients of lenvatinib; (6) Those who are known to be allergic to the active ingredients or excipients of Sintilizumab; (7) A history of liver resection, liver transplantation, interventional therapy, and other malignant tumors; (8) Women who are pregnant or breast-feeding; those with fertility who are unwilling or unable to take effective contraceptive measures; (9) Patients with grade II or higher myocardial ischemia or myocardial infarction, poorly controlled arrhythmia (including QTc interval ≥470 ms); according to NYHA standards, grade III to IV cardiac insufficiency, or cardiac color Doppler ultrasound examination suggests left ventricular ejaculation Blood score LVEF<50%; (10) Abnormal coagulation function (INR>1.5 or prothrombin time (PT)>ULN+4 seconds or APTT>1.5 ULN), have bleeding tendency or are receiving thrombolytic or anticoagulant therapy; (11) Have a mental illness or a history of psychotropic drug abuse; (12) Combined with HIV-infected patients; (13) Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation; (14) Patients with active infection; (15) Patients with poor compliance such as floating population; (16) Have received the following therapies in the past: anti-PD-1, anti-PD-L1 or anti-PD-L2 drugs or for another stimulating or synergistic inhibition of T cell receptors (for example, CTLA-4, OX-40, CD137) medicine; (17) An active autoimmune disease that requires systemic treatment (such as the use of disease-relieving drugs, glucocorticoids, or immunosuppressive agents) occurred within 2 years before the first administration. Replacement therapies (such as thyroxine, insulin, or physiological glucocorticoids for adrenal or pituitary insufficiency, etc.) are not considered systemic treatments; (18) Are receiving systemic glucocorticoid therapy (excluding nasal spray, inhalation or other local glucocorticoids) or any other form of immunosuppressive therapy within 7 days before the first administration of the study; Note: physiological doses are allowed Glucocorticoids (≤10 mg/day prednisone or equivalent); (19) There is clinically uncontrollable pleural effusion/abdominal effusion (patients who do not need to drain the effusion or stop drainage for 3 days without a significant increase in effusion can be included in the group); (20) Acute or chronic active hepatitis B or C infection, HBV DNA ≥ 200000IU/ml or 106 copies/ml when Sintilimab is treated; hepatitis C virus HCV RNA ≥ 103 copies/ml; Hepatitis B surface anti-(HbsAg) and anti-HCV antibodies are positive at the same time.

(21) Live vaccine has been vaccinated within 30 days before the first dose (cycle 1, day 1); Note: It is allowed to receive the inactivated virus vaccine for seasonal influenza injection within 30 days before the first dose; but it is not allowed to receive intranasal vaccine Medicated live attenuated influenza vaccine.

(22) The researcher believes that it is not suitable for inclusion in the group.