Phase I/II Study of Anti-PD-1/PD-L1 Antibodies Combined With S-adenosyl-methionine in Patients With Advanced-Stage Hepatocellular Carcinoma
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Incidence of adverse events
研究概览
简要总结
This study is being done to analyze the safety, tolerability, and efficacy of treatment using combination of SAM and anti-PD-1/PDL1 antibodies for patients with advanced hepatocellular carcinoma.
详细描述
This is a study of combination anti-PD-1/PD-L1 antibodies and S-adenosyl-methionine (SAM) for adult patients (≥18) with advanced hepatocellular carcinoma.
SAM is a compound found naturally in the body and is available as a dietary supplement in the U.S. SAM is a prescription drug in China treating liver disease and advanced HCC with poor liver function under certain circumstances. Also, SAM has recently been shown to play a key role regulating cancer cell proliferation trough epigenetic pathway.
Anti-PD-1/PD-L1 antibodies (including pembrolizumab, nivolumab, sintilimab, toripalimab, camrelizumab, 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 SAM and PD-1/PD-L1 monoclonal antibody in unresectable late-stage HCC patients.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥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.
排除标准
- •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;
研究组 & 干预措施
Anti-PD-1/PD-L1 antibodies and S-adenosyl-methionine combination
Drug: Anti-PD-1/PD-L1 Intravenous injection for at least 6 months
Drug: S-adenosyl-methionine Taken orally for at least 6 months
干预措施: Anti-PD-1/PD-L1 (Drug)
Anti-PD-1/PD-L1 antibodies and S-adenosyl-methionine combination
Drug: Anti-PD-1/PD-L1 Intravenous injection for at least 6 months
Drug: S-adenosyl-methionine Taken orally for at least 6 months
干预措施: S-Adenosyl-Methionine (Drug)
结局指标
主要结局
Incidence of adverse events
时间窗: Up to 30 days after last treatment dose
Safety will be monitored by addressing and recording all adverse events (AEs), serious adverse events (SAEs) and specific laboratory abnormalities (worst grade). Toxicities will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.
次要结局
- 6-month survival rate(6 months)
- Progression free survival(PFS)(2 years)
- Duration of relief(DOR)(2 years)
- 12-month survival rate(12 months)
- Objective response rate(ORR)(2 years)
- To the relief time (TOR)(2 years)
- Disease Control Rate (DCR)(2 years)