Anti-PD-1/PD-L1 Antibodies Plus Anti-VEGF Antibody Treatment in Patients With Advanced-Stage HCC

Официальное название

Phase I/II Study of Anti-PD-1/PD-L1 Antibodies Combined With Anti-VEGF Antibody Treatment in Patients With Advanced-Stage Hepatocellular Carcinoma

Обзор

This study is being done to analyze the safety, tolerability, and efficacy of treatment using combination of anti-VEGF and anti-PD-1/PDL1 antibodies for patients with advanced hepatocellular carcinoma.

Подробное описание

This is a study of combination anti-PD-1/PD-L1 antibodies and anti-VEGF for adult patients (≥18) with advanced hepatocellular carcinoma.

Anti-VEGF (including Avastin, IBI305 etc.) is designed to block a protein called vascular endothelial growth factor, therefore blocking the blood supply that feeds the tumor. Also, Anti-VEGF has recently been shown to play a key role regulating cancer cell proliferation trough epigenetic pathway.

Anti-PD-1/PD-L1 antibodies (including pembrolizumeb, nivolumab, sintilimab, toripalimab, camrelizumeb, tislelizumab and atezolizumab etc.) are given intravenously at assigned dose. Treatment may continue until disease progression, intolerable toxicity, or consent withdrawal.

This study is aimed to evaluate the safety and efficacy of the combination of anti-VEGF and PD-1/PD-L1 mAb in unresectable late-stage HCC patients.

Вмешательства

• Препарат Anti-PD-1/PD-L1 antibodies
  Anti-PD-1/PD-L1 Intravenous injection for at least 6 months
• Препарат Anti-VEGF
  Anti-VEGF Intravenous injection for at least 6 months

Первичные конечные точки

• Incidence of adverse events [Срок оценки: Up to 30 days after last treatment dose]

Вторичные конечные точки (7)

• Objective response rate(ORR) [Срок оценки: 5 years]
• Progression free survival(PFS) [Срок оценки: 5 years]
• To the relief time (TOR) [Срок оценки: 5 years]
• Duration of relief(DOR) [Срок оценки: 5 years]
• Disease Control Rate (DCR) [Срок оценки: 5 years]
• 6-month survival rate [Срок оценки: 6-month]
• 12-month survival rate [Срок оценки: 12-month]

Критерии участия

Критерии включения

• ≥18 years old, male or female
• Advanced hepatocellular carcinoma (cannot be removed or metastasized) diagnosed clinically or pathologically, at least one measurable lesion without local treatment, Child-Pugh A ;Barcelona Clinic Liver Cancer(BCLC) staging is stage B or C
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
• Patient has given written informed consent.
• The function of important organs meets the requirements
• Expected survival ≥12 weeks
• Non-surgical sterilization or women of childbearing age need to use a medically-accepted contraceptive (such as an intrauterine device, contraceptive or condom) during the study period and within 3 months after the end of the study treatment period.

Критерии исключения

• The patient has any active autoimmune disease or a history of autoimmune disease (such as the following, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, thyroid Hyperfunction; patients with vitiligo; complete remission of asthma in childhood, can be included without any intervention after adulthood; asthma patients who require bronchodilators for medical intervention cannot be included);
• The patient is using immunosuppressive agents or systemic hormonal therapy to achieve immunosuppressive purposes (agents amount > 10 mg / day of prednisone or other therapeutic hormones), and continue to use within 2 weeks before enrollment;
• Have clinical symptoms or disease that are not well controlled;
• Significant clinically significant bleeding symptoms or a clear bleeding tendency within 3 months prior to randomization;
• Arterial/venous thrombosis in the first 6 months of randomization
• According to the investigator, the patient has other factors that may affect the results of the study or lead to the termination of the study, such as alcohol abuse, drug abuse, other serious diseases (including mental illness) requiring combined treatment, and serious laboratory abnormalities.#with family or social factors, it will affect the safety of patients.
• Liver tumor burden greater than 50% of the total liver volume, or patients who have previously undergone liver transplantation;Known for a history of central nervous system metastasis or hepatic encephalopathy;Severe allergic reactions to other monoclonal antibodies;

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

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Китай · 1 центр

• Zhongshan Hospital Fudan university — Шанхай

Публикации

• Zhou J, Sun H, Wang Z, Cong W, Wang J, Zeng M, Zhou W, Bie P, Liu L, Wen T, Han G, Wang M, Liu R, Lu L, Ren Z, Chen M, Zeng Z, Liang P, Liang C, Chen M, Yan F, Wang W, Ji Y, Yun J, Cai D, Chen Y, Cheng W, Cheng S, Dai C, Guo W, Hua B, Huang X, Jia W, Li Y, Li Y, Liang J, Liu T, Lv G, Mao Y, Peng T, Ren W, Shi H, Shi G, Tao K, Wang W, Wang X, Wang Z, Xiang B, Xing B, Xu J, Yang J, Yang J, Yang Y, Y PMID 33442540
• Finn RS, Ryoo BY, Merle P, Kudo M, Bouattour M, Lim HY, Breder V, Edeline J, Chao Y, Ogasawara S, Yau T, Garrido M, Chan SL, Knox J, Daniele B, Ebbinghaus SW, Chen E, Siegel AB, Zhu AX, Cheng AL; KEYNOTE-240 investigators. Pembrolizumab As Second-Line Therapy in Patients With Advanced Hepatocellular Carcinoma in KEYNOTE-240: A Randomized, Double-Blind, Phase III Trial. J Clin Oncol. 2020 Jan 20;38 PMID 31790344
• Ren Z, Xu J, Bai Y, Xu A, Cang S, Du C, Li Q, Lu Y, Chen Y, Guo Y, Chen Z, Liu B, Jia W, Wu J, Wang J, Shao G, Zhang B, Shan Y, Meng Z, Wu J, Gu S, Yang W, Liu C, Shi X, Gao Z, Yin T, Cui J, Huang M, Xing B, Mao Y, Teng G, Qin Y, Wang J, Xia F, Yin G, Yang Y, Chen M, Wang Y, Zhou H, Fan J; ORIENT-32 study group. Sintilimab plus a bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hep PMID 34143971

Идентификаторы

NCT: NCT06537908 · B2024-104

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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