A Phase II/III Trial of Comparison of Benefit of Administration of Checkpoint Inhibitors Plus Chemodrug Via Artery or Fine Needle to Tumor Versus Vein for Immunotherapy of Advanced Solid Tumors
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Overall survival
研究概览
简要总结
This trial was designed to investigate the safety, response rates and survival outcomes of patients with advanced solid tumors by trans-artery/intra-tumor infusion of PD1/PDL1 antibody and/or CTLA4 antibody ipilimumab plus chemotherapeutic drug and to compare their differences.
详细描述
Malignant solid tumors including lung and liver cancers are the most common malignancy worldwide, and their mortality rates are very high. China has a huge population base, with about 4,000,000 new cases each year. More than 60% of the solid tumors in China are diagnosed at mid-to-late stage and have lost the chance of surgery. Recently a lot of therapeutic strategies have been developed and applied to clinic including targeted therapy and immunotherapy, but the overall efficiency is still low. It is difficult to be widely used in patients with advanced solid cancers, and more alternative therapies are urgently needed.
Antibodies against PD1, PDL1 and CTLA4 are representative drugs for the check-points inhibitory agents, and their clinical indications have been approved in various types of tumors, including advanced melanoma, non-small cell lung cancer, renal cell carcinoma, and classical Hodgkin's lymphoma and late recurrent head and neck squamous cell carcinoma patients, et al. Those drugs are regularly systemically administrated by vein infusion, however, local delivery of those drugs via interventional radiology technique including trans-artery or intra-tumor injection may increase the local drug concentration in the tumor, improve the efficacy, and reduce systemic adverse reactions, through so called "first pass effect" of drug on target organs. To the investigator's knowledge, no studies have been developed on the efficacy and survival benefit of localized delivery of checkpoint inhibitors for treatment of cancer patients. This phase II-III clinical trial was designed to compare the effects of Pembrolizumab, Tecentriq, et al and/or ipilimumab plus chemotherapeutic drug such as doxorubicin on the survival benefit of patients with advanced solid cancers, including ORR, DCR, median survival time, and safety.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Cytohistological confirmation is required for diagnosis of cancer.
- •Signed informed consent before recruiting.
- •Age above 18 years with estimated survival over 3 months.
- •Child-Pugh class A or B/Child score > 7; ECOG score < 2
- •Tolerable coagulation function or reversible coagulation disorders
- •Laboratory examination test within 7 days prior to procedure: WBC≥3.0×10E9/L; Hb≥90g/L； PLT ≥50×10E9/L；INR < 2.3 or PT < 6 seconds above control；Cr ≤ 145.5 umul/L；Albumin > 28 g/L；Total bilirubin < 51 μmol/L
- •At least one tumor lesion meeting measurable disease criteria as determined by RECIST v1.
- •Birth control.
- •Willing and able to comply with scheduled visits, treatment plan and laboratory tests.
排除标准
- •Patients participated in clinical trials of equipment or drugs (signed informed consent) within 4 weeks;
- •Patients accompany by ascites, hepatic encephalopathy and esophageal and gastric varices bleeding;
- •Any serious accompanying disease, which is expected to have an unknown, impact on the prognosis, include heart disease, inadequately controlled diabetes and psychiatric disorders;
- •Patients accompanied with other tumors or past medical history of malignancy;
- •Pregnant or lactating patients, all patients participating in this trial must adopt appropriate birth control measures during treatment;
- •Patients have poor compliance.
- •Any contraindications for hepatic arterial infusion procedure:
- •A.Impaired clotting test (platelet count < 60000/mm3, prothrombin activity < 50%).
- •B.Renal failure / insufficiency requiring hemo-or peritoneal dialysis. C.Known severe atheromatosis. D.Known uncontrolled blood hypertension (> 160/100 mm/Hg).
- •Allergic to contrast agent;
- •Any agents which could affect the absorption or pharmacokinetics of the study drugs
- •Other conditions that investigator decides not suitable for the trial.
研究组 & 干预措施
Pembrolizumab via localized infusion
This group dividied into two subgroups:
- Checkpoint inhibitor (CPI) such as Pembrolizumab ± Ipilimumab is administrated with a dose of 1-2mg/kg via sustained (10min) micro-pump infusion via artery, plus chemotherapy, every 3 weeks.
- Checkpoint inhibitor (CPI) such as Pembrolizumab ± Ipilimumab is administrated with a total dose of 150mg via intra-tumor fine needle injection in 5 min, plus doxorubicin, every 3 weeks.
干预措施: Checkpoint inhibitor (CPI) such as Pembrolizumab plus chemotherapy (Drug)
Checkpoint inhibitor (CPI) Pembrolizumab plus chemotherapy via vein infusion
Checkpoint inhibitor (CPI) such as Pembrolizumab is administrated with a total dose of 2mg/kg via vein infusion (30 min), plus chemotherpy every 3 weeks.
干预措施: Checkpoint inhibitor (CPI) such as Pembrolizumab plus chemotherapy (Drug)
结局指标
主要结局
Overall survival
时间窗: 5 years
Overall survival (OS) will be defined as the elapsed time from the enrollment to death from any cause. For surviving patients, follow-up will be censored at the date of last contact (or last date known to be alive). Follow-up for OS will occur every 12 weeks (±1 month) until death or withdrawal of consent from the study.
Complete response (CR) rate before or at Month 6
时间窗: 4
Percentage of patients achieving complete response (CR) before or at Month 6
次要结局
- Disease control rate(5 years)
- Progression-free survival(5 years)
- Duration of remission (DOR)(5 years)
- Cause of death (COD) when appropriate(5)