Effects of Neoadjuvant Immunotherapy on Anti-tumour Immunity in Hepatocellular Carcinoma Patients Undergoing Liver Resection

Обзор

Our study aims to evaluate the benefit of the administration of immunotherapy (atezolizumab), in patients with hepatocellular carcinoma (HCC), prior surgical resection of the tumor. HCC is the most prevalent primary liver cancer, responsible for nearly 800,000 deaths annually, making it the third leading cause of cancer-related mortality worldwide. Ablation by radiologic micro-waves or surgical resection represent at the moment the only curative therapies for early stages of the disease. Despite these curative options, HCC recurrence is frequent. Recently, immunotherapy has demonstrated good results on patient overall survival for advanced stages of HCC in comparison to sorafenib. Because of the beneficial effect of immunotherapy on HCC, several groups have attempt to use it as adjuvant therapy in order to reduce the recurrence rate. However the results are at the moment controversial. One can hypothetize that postoperative inflammation and liver regeneration can negatively impact the effect of the immunotherapy. Therefore, the administration of the treatmeent before surgical resection could overcome this issue.

Вмешательства

• Препарат Atezolizumab
  Patients will receive two doses of atzolizumab 6 and 3 weeks before surgery

Первичные конечные точки

• Difference in frequency of flow cytometry-assessed HCC-specific CD8+ cells in the periphery (PBMC) between patients with vs without ICI therapy prior to liver surgery [Срок оценки: Four years]

Вторичные конечные точки (3)

• Tumor microenvironment changes induced by ICI therapy [Срок оценки: four years]
• Overall survival and recurrence free survival [Срок оценки: four years]
• Tumor burden [Срок оценки: Four years]

Критерии участия

Критерии включения

• All adult patients undergoing liver resection for HCC at the Geneva University Hospitals (HUG), with prior informed and signed consent.
• Patients of childbearing age must be willing to use a contraception at the day of inclusion and for at least 5 months after the last infusion.
• Negative pregnancy test at inclusion
• Patients will require to be eligible for surgical resection according to the BCLC guidelines (very early to early stage with preserved liver function and good patient condition) (4).
• The control group will include data from the patients in our ongoing research project (study protocol 2023-02372), undergoing liver resection without prior ICI therapy (n = 30).

Критерии исключения

• Patients who do not ultimately undergo liver resection due to unforeseen reasons (this happens rarely, such as in the presence of unexpected HCC progression discovered during surgery).
• Patients with an ongoing pregnancy (an unlikely event, as non-surgical HCC treatments would be prioritized in such cases).
• Patients unable to follow procedures due to language barriers, insufficient comprehension of project language, or unable to give consent.
• Patients <18 years.
• Patients with medical history of allergy or severe AEs to ICI therapy
• Pregnant and/or breastfeeding women. Lactating women should stop lactation or will be excluded from the study as breastfeeding under atezolizumab is not recommended. Furthermore, breastfeeding is not recommended for at least 5 months after the last dose.
• Immunosuppressed patients and patients with haematological disorder leading to a deficient immunity
• Patients with hepatic and/or cardiovascular deficiencies that contra-indicate surgery. Compensated cirrhotic patients are expected and will be included in the study as no dosage modification of the atezolizumab is required for these patients.
• Patients who received a live or attenuated vaccine in the last 28 days before inclusion in the study.
• Patients with untreated Hepatitis B and/or C or HIV. HIV patients under treatment with normal CD4 counts can be included. Hepatitis B and/or C patients under antiviral therapies can be included.
• Patients with history of inflammatory pneumopathy, active brain metastasis and patients treated with a systemic immunotherapy in the last 6 months.
• Patients under steroid treatment during the inclusion will be excluded.

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

Швейцария · 1 центр

• Geneva University Hospitals — Geneva

Идентификаторы

NCT: NCT07461675 · HCCsurgICI2025

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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