Sequential FOLFOX-HAIC-TACE Plus Sintilimab-Bevacizumab Neoadjuvant Therapy Versus Direct Resection in Resectable High-Risk Recurrence Hepatocellular Carcinoma

Официальное название

Efficacy and Safety of Sequential FOLFOX-HAIC Followed by TACE Combined With Sintilimab Plus Bevacizumab as Neoadjuvant Therapy, Followed by Surgical Resection, Versus Direct Surgical Resection in Patients With Resectable Hepatocellular Carcinoma and High-Risk Recurrence Factors: A Single-Center, Open-Label, Two-Arm, Randomized Study

Обзор

This study is designed to evaluate the efficacy and safety of sintilimab-bevacizumab doublet combined with FOLFOX-HAIC and TACE as the perioperative adjuvant therapy in surgical resection to hepatocellular carcinoma with high-risk features. (1) Evaluate for some high-risk patients with resectable tumours, whether or not sintilimab-bevacizumab doublet combined with FOLFOX-HAIC and TACE reduces the risk of recurrence and improves the survival of patients. (2) Evaluate the safety of sintilimab-bevacizumab doublet combined with FOLFOX-HAIC and TACE for the neoadjuvant therapy of resectable hepatocellular carcinoma.

Вмешательства

• Препарат FOLFOX regimen
  oxaliplatin 85 mg/m² intra-arterial infusion over 2 hours; leucovorin calcium 200 mg/m² intra-arterial infusion over 2 hours; 5-fluorouracil 400 mg/m² intra-arterial bolus followed by 2400 mg/m² continuous intra-arterial infusion over 46 hours
• Препарат Immunotherapy
  sintilimab (200 mg intravenous infusion, q3w)
• Препарат targeted therapy
  bevacizumab (15 mg/kg intravenous infusion, q3w)
• Устройство cTACE
  conventional transarterial chemoembolization

Первичные конечные точки

• 2y-RFS [Срок оценки: From date of randomization until date of first documented recurrence or death from any cause, whichever occurs first, assessed up to 2 years]

Вторичные конечные точки (5)

• pCR [Срок оценки: Perioperative]
• MPR [Срок оценки: Perioperative]
• ORR [Срок оценки: Perioperative]
• R0 resection rate [Срок оценки: Perioperative]
• EFS [Срок оценки: the time from randomization to the first occurrence of any of the following events: disease progression precluding surgery, local or distant recurrence, or death from any cause，assessed up to 2 years]

Критерии участия

Критерии включения

1.Fully understanding and voluntarily signing the informed consent form, complying with the requirements and evaluation schedule of this study; 2.18 to 75 years old; 3.Hepatocellular carcinoma diagnosed by histopathology; 4.Imaging examination results meeting the definition of high-risk recurrence risk factors in this study: 2-4 multiple tumors; the size of the dominant tumor was >=5 cm; CNLC-Ⅲa incorporated with portal vein tumor thrombus \[Vp1/2/3\]; 5.Surgical evalution with a radically resectable tumor; 6.Child-Pugh class A; 7.ECOG PS： 0\~1; 8.hepatocellular carcinoma who had never received previous form of systemic therapy; 9.At least one measurable lesion that can be accurately assessed by computed tomography (CT) or magnetic resonance imaging (MRI) and is suitable for assessment per mRECIST 1.1; 10.The main organ functions are normal, including the following criteria: (1) sufficient bone marrow function, defined as neutrophils ≥ 1.5 × 10 \^ 9/L, hemoglobin (Hb) ≥ 90 g/dL, platelets ≥ 50 × 10 \^ 9/L; (2) good liver function, defined as serum total bilirubin ≤ 1.5 × ULN, aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 × ULN, albumin ≥ 28 g/L; (3) good coagulation function, defined as international normalized ratio (INR) ≤ 2.3 or prothrombin time (PT) exceeding the normal control range ≤ 3 seconds; (4) Adequate renal function， defined as glomerular filtration rate (GFR)>90mL/min; 11.Female participants of childbearing potential have negative results on a pregancy test in 3 days before the first utilization of medicine and male or female participants with partners of child-bearing potential had to use a medically acceptable method of contraception through 180 days after taking study drug

Критерии исключения

• Pregnant or lactating women;
• Patients with a history of other malignancies within the past 5 years, excluding basal cell carcinoma of the skin， cervical carcinoma in situ and/or thyroid papillary carcinoma have been cured;
• Patients who are known to be allergic to the trial drugs, finolizumab and bevacizumab；
• Previous history of upper gastrointestinal bleeding or current presence of a clear bleeding risk disease;
• Patients with uncontrolled cardiac clinical symptoms or diseases；
• Uncontrolled cardiac symptoms or diseases, including but not limited to (1) heart failure above NYHA class II, (2) unstable angina, (3) myocardial infarction within 1 year, and (4) clinically important significant supraventricular or ventricular arrhythmias requiring clinical intervention；
• Patients with any active autoimmune disease or history of autoimmune disease；
• Have a history of immune deficiency, including HIV-positive test results, or suffer from other acquired or congenital immune deficiency diseases, or have a history of organ transplantation and bone marrow transplantation;
• History of mental illness, and abuse of psychiatric drugs and narcotics;
• Severe uncontrolled recurrent infections or other serious uncontrolled concomitant diseases;
• Situations that researchers assessed as unsuitable for inclusion in this study.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07522411 · GDZL032

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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