Tislelizumab or Tislelizumab Combined With Lenvatinib Neo-adjuvant Treatment for Resectable RHCC

Официальное название

Tislelizumab or Tislelizumab Combined With Lenvatinib Neo-adjuvant Treatment for Resectable Recurrent Hepatocellular Carcinoma：Phase II Non-randomized Control Clinical Trial

Обзор

This non-randomized phase II clinical trial aimed to explore the efficacy and safety of Tislelizumab or Tislelizumab combined with Lenvatinib as neoadjuvant treatment for resectable RHCC patients

Подробное описание

Hepatocellular carcinoma (HCC) patients have about 70% of 5-year recurrence rate after curative treatment. Only 30% of recurrent HCC (RHCC) patients are resectable when diagnosed. Neoadjuvant treatment may reduce tumor burden and recurrence rate after surgery for RHCC patients. Immune checkpoint inhibitors combined with or without antiangiogenic agents have already been reported effective in advanced HCC patients as first-line therapy, and in several early-stage solid tumors as neoadjuvant therapy. According to several preclinical results, immune infiltration and the expression of PD-1 were higher in RHCC tumors than in paired primary tumors. So, immune checkpoint inhibitors combined with or without antiangiogenic agents might have a better response in RHCC patients than primary HCC patients. Herein, we designed this phase II clinical trial to explore the efficacy and safety of Tislelizumab (PD-1 inhibitor) or Tislelizumab combined with Lenvatinib as neoadjuvant treatment for resectable RHCC patients. Enrolled resectable RHCC patients will be divided into two non-randomized seperate arms, sequentially (arm 1: neoadjuvant tislelizumab; arm 2: neoadjuvant tislelizumab and lenvatinib). Each arm was estimated to enroll 40 patients. We have already enrolled 17 patients in arm 1, and have terminated the enrollment of arm 1 due to modest treatment responses. The enrollment of arm 2 is ongoing.

Вмешательства

• Препарат Tislelizumab
  Patients receive Tislelizumab on week 1 and week 4 (200mg, iv, q3w). After 2 cycles of Tislelizumab and evaluation of resectability, patients will receive surgery in 6 weeks after enrollment. Patients will receive Tislelizumab for 1 year (200mg, iv, q3w, 17 cycles) in 4-6 weeks after surgery.
• Препарат Tislelizumab combined with Levatinib
  Patients receive Tislelizumab on week 1 and week 4 (200mg, iv, q3w); Lenvatinib from Day1 to Day 28 (8/12mg qd). After neoadjuvant treatment and evaluation of resectability, patients will receive surgery in 6weeks after enrollment. Patients will receive Tislelizumab combined with Lenvatinib for 1 year in 4-6 weeks after surgery.

Первичные конечные точки

• Disease-free survival rate [Срок оценки: 1 year]

Вторичные конечные точки (3)

• Objective response rate [Срок оценки: At time of surgery]
• Incidence of severe adverse events [Срок оценки: Three months after treatment]
• Major pathological response rate [Срок оценки: At time of surgery]

Критерии участия

Критерии включения

• Diagnosed as recurrent hepatocellular carcinoma after curative treatment;
• The criteria for resectability is met;
• Has at least one evaluable lesion according to the RECIST 1.1 standard and has not received local treatment;
• Eastern Cooperative Oncology Group score 0-1, Child-pugh score 5-7;
• Agree to biopsy and blood sample collection;
• Adequate organ and marrow function.

Критерии исключения

• Previously received any transarterial chemoembolization and immune therapy and other local or systemic liver cancer treatments, except for curative ablation;
• Extrahepatic metastasis;
• History of gastroesophageal varices or active cardia ulcers associated with a high risk of bleeding;
• History of autoimmune disease or need to take immunosuppressant drugs for a long time;
• History of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS);
• Abnormal organ function

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• The First Affiliated Hospital of Sun Yat-sen University — Гуанчжоу

Идентификаторы

NCT: NCT04615143 · RHCC2020

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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