Clinical Study on the Effectiveness and Safety of Lenvatinib As Adjuvant Treatment for Patients with High-risk Recurrence of Hepatocellular Carcinoma After Surgery

Обзор

This study is a prospective, randomized, controlled, open, phase II, multicenter clinical study, which aims to evaluate the efficacy and safety of lenvatinib for adjuvant treatment of high-risk recurrent liver cancer after radical surgery. This study is divided into 3 stages: screening period (screening period 28 days), treatment period (up to 12 months, or until any of the following occurs, whichever occurs first: ① The subject has an intolerable toxic reaction and is still not relieved after dose adjustment; ② The subject's first imaging confirmed disease recurrence or withdrew from the study for other reasons), and follow-up period (12 months after the end of treatment). Dosage regimen: Eligible subjects were randomly assigned to the experimental group or the control group in a 2:1 ratio, with surgical method (radical surgery vs ablation) as the stratification factor. The experimental group received lenvatinib treatment, and the control group received best supportive care

Вмешательства

• Препарат Postoperative adjuvant lenvatinib
  Follow the instructions and take lenvatinib 8 mg (body weight ≤ 60Kg) or 12 mg (body weight ≥ 60Kg) orally once a day.
• Другое Supportive care measures
  Adjuvant treatments such as antiviral, TACE, HAIC, radiotherapy, and systemic antitumor therapy can be used

Первичные конечные точки

• 1-year cumulative recurrence-free patient percentage [Срок оценки: The patient started taking lenvatinib after radical surgery for hepatocellular carcinoma and continued treatment for up to 1 year.]

Вторичные конечные точки (4)

• Recurrence Free Survival [Срок оценки: The patient started taking lenvatinib after radical surgery for hepatocellular carcinoma and continued treatment for up to 3 years.]
• Overall Survival [Срок оценки: The time span from the date of surgery to the date of the patient's last follow-up visit or death, assessed up to 3 years.]
• Time To Recurrence [Срок оценки: The time span from the date of radical liver resection to the date of first documented tumor recurrence, assessed up to 3 years.]
• Diachronic changes in quality of life scores based on FACT-Hep scale [Срок оценки: From enrollment date to database deadline, assessed up to 3 years.]

Критерии участия

Критерии включения

• Certainly, here is the translation of the provided text into English:

• Age between 18 to 80 years old, gender not limited;
• Received radical treatment surgery for liver cancer within 4 to 8 weeks prior to enrollment, and meet the following criteria: (1) Intraoperative judgment criteria: ① No gross tumor thrombus in the hepatic vein, portal vein, bile duct, and inferior vena cava; ② No invasion of adjacent organs, no hepatic hilum lymph nodes or distant metastasis; ③ The liver resection margin is ≥1cm from the tumor border; if the margin is less than 1cm, the histological examination of the resected liver surface shows no residual tumor cells, i.e., negative resection margin. (2) Postoperative judgment criteria: ① Ultrasound, computed tomography(CT), magnetic resonance imaging(MRI) examinations (at least two of these) are performed within 1 to 2 months after surgery, with no residual or recurrent tumor lesions in radical resection cases, and no active tumor lesions in radical ablation cases; ② If serum alpha-fetoprotein(AFP), des-gamma-carboxy prothrombin(DCP), and a combination of 7 Micro ribonucleic acid(microRNAs) and other tumor markers were elevated before surgery, then quantitative measurement of tumor markers is required 8 weeks after surgery, and their levels drop to the normal range; if serum alpha-fetoprotein(AFP) does not return to normal within 8 weeks after surgery , will not be included.
• Postoperative pathological examination confirms hepatocellular carcinoma(HCC), and all tumor nodules are completely removed with negative resection margins.
• Imaging examinations ≥4 weeks after surgery confirm no recurrence or metastasis.
• Expected survival >3 months;
• hepatitis B virus(HBV) deoxyribonucleic acid(DNA) <10\^4 copies/ml (2000 IU/ml), if hepatitis B virus(HBV) deoxyribonucleic acid(DNA) ≥10\^4 copies/ml, antiviral treatment should be initiated first until hepatitis B virus(HBV) deoxyribonucleic acid(DNA) is reduced to below 10\^4 copies/ml before entering the study, and continue to take antiviral medication and monitor liver function and hepatitis B virus(HBV) load.
• At least one of the following high recurrence risk factors exists:

<!-- -->

• Tumor diameter >5cm
• Multiple lesions (>3)
• Pathology indicates MVI positivity
• Edmondson III-IV grade
• Persistently abnormal alpha-fetoprotein 8. No history of other tumors, and no antitumor treatment before surgery; 9. Eastern Cooperative Oncology Group(ECOG) score: 0-1. 10. Major organ functions are normal, i.e., meeting the following criteria:

Hematology examination (within 14 days before screening, without blood transfusion or use of granulocyte colony stimulating factor(G-CSF)):

• Hemoglobin ≥90 g/L;
• Absolute neutrophil count (ANC) ≥1.5×10\^9/L;
• Platelet count ≥75×10\^9/L;

Biochemical examination (within 14 days before screening, without the use of albumin):

• Albumin ≥28 g/L;
• Total bilirubin ≤1.5×upper limit of normal (ULN);
• Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) ≤3×ULN;
• Creatinine ≤1.5×ULN;

Coagulation function:

• International normalized ratio (INR) or prothrombin time (PT) ≤1.5×ULN;
• Activated partial thromboplastin time (APTT) ≤1.5×ULN. 11.Patients with reproductive capacity, both male and female, must use reliable contraceptive measures during the study medication use and for 60 days after the last dose.

Критерии исключения

• Here is the translation of the provided text into English:

• Pathologically diagnosed as a mixed type of hepatocellular carcinoma-intrahepatic cholangiocarcinoma (HCC-ICC).
• Positive surgical margins or tumor rupture.
• Reoperation for recurrent liver cancer.
• History of other malignancies within 5 years, unless the patient has undergone potentially curative treatment and has no evidence of the disease for 5 years, except for patients who have successfully undergone resection surgery for skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ, or other carcinoma in situ (the 5-year requirement does not apply).
• Past or current congenital or acquired immunodeficiency diseases.
• Patients who have undergone allogeneic transplantation.
• Insufficient biopsy and/or surgical samples are unavailable.
• Pregnant and breastfeeding patients.
• Received targeted drug therapy such as sorafenib, lenvatinib, regorafenib, or immunomodulatory therapy such as anti-PD-1, anti-PD-L1, anti-CTLA-4 before surgery.
• Unable to provide informed consent (due to language, intellectual capacity, etc.).
• Active bleeding or coagulation abnormalities, with a tendency to bleed or currently undergoing thrombolytic, anticoagulant, or antiplatelet therapy.
• History of gastrointestinal bleeding within the past 4 weeks or a clear tendency towards gastrointestinal bleeding (e.g., known active local ulcer lesions, fecal occult blood ++ or more, if persistent fecal occult blood +, gastroscopy should be performed), or other conditions that may cause gastrointestinal bleeding as determined by the investigator (e.g., severe gastric fundus/esophageal varices).
• Significant clinically meaningful cardiovascular diseases, including but not limited to acute myocardial infarction, severe/unstable angina, or coronary artery bypass grafting within the past 6 months, congestive heart failure (New York Heart Association NYHA class >2), arrhythmias that are poorly controlled or require pacemaker treatment, uncontrolled hypertension with medication (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg).
• Allergy to chemotherapy drugs or contraindications to surgery.
• History of thrombosis or thromboembolic events within the past 6 months, such as stroke and/or transient ischemic attack, deep vein thrombosis, pulmonary embolism, etc.
• History of gastrointestinal perforation, abdominal fistula, or intra-abdominal abscess within the past 6 months.
• Not yet recovered from surgery, such as having unhealed incisions or severe postoperative complications.
• History of alcohol, psychotropic drugs, or other drug abuse within the past 6 months.
• Presence of other serious diseases that the investigator deems unsuitable for participation in this study;
• Currently participating in other therapeutic/interventional clinical trials.

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

Китай · 1 центр

• The First Affiliated Hospital of Nanjing Medical University — Нанкин

Идентификаторы

NCT: NCT06762782 · 2024-SR-708

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗