Phase II Study of Neoadjuvant CT-Guided Intra-tumor Double Checkpoint Blockades for Untreated Hepatocellular Carcinoma (HCC) Amenable for Surgical Resection
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- pCR rate for the study groups
研究概览
简要总结
This trial is designed to investigate the safety, response rates and survival outcomes of patients with hepatocellular carcinoma by delivery of CTLA4 and PD1 or PDL1 antibodies combination through CT-guided intra-tumor (IT) injection.
详细描述
Antibodies against CTLA4, PD1 or PDL1 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 of the tumor, improve the efficacy, and reduce systemic adverse reactions. CTLA4 antibody ipilimumab has been widely effectively using to combine with PD1 or PDL1 antibody and this study is to combine ipilimumab and PD1 antibody or PDL1 antibody, so called double checkpoint inhibitors combination therapy, as neoadjuvant therapy for hepatocellular carcinoma (HCC) via intra-tumor admistration. To the investigator's knowledge, no studies have been developed on the safety, efficacy and survival benefit of the double checkpoint inhibitors combination therapy for cancer patients as neoadjuvant treatment via intra-tumor delivery. This phase II clinical trial is designed to assess the safety and survival benefit of ipilimumab and pembrolizumab or durvalumab combination with or without chemodrug or bevacizumab as neoaduvant therapy on patients with HCC, including safety, pCR, mPR, PFS, ORR, DCR, and median survival time.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed previously untreated hepatocellular carcinoma (HCC). If a diagnostic biopsy is available, a pre-treatment biopsy is not required. Patients with a suspected HCC are eligible, but pathology must be confirmed prior to initiating treatment on study.
- •The patient must be a suitable candidate for surgery, in the opinion of the treating physician.
- •Signed and dated written informed consent must be provided by the patient prior to admission to the study in accordance with International Conference on Harmonization-Good Clinical Practice (ICH-GCP) guidelines and to the local legislation.
- •Eastern Cooperative Oncology Group (ECOG) performance status score 0-1
- •Absolute neutrophil count (ANC) >= 1.5 x 10^9/L; Hemoglobin >= 8.0 g/dL; Platelets >= 100 x 10^9/L; Total bilirubin =< 1.5 x upper limit of normal (ULN) (except subjects with Gilbert syndrome who can have total bilirubin < 3.0 mg/dL); Creatinine =< 1.5 x ULN or calculated creatinine clearance >= 50 mL/min using Cockcroft-Gault formula for creatinine clearance calculation OR 24-hour urine creatinine clearance >= 50 mL/min.
- •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. 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
Group 1: IT injection of double ICIs
Neoadjuvant therapy: intra-tumor injection of double ICIs only.
干预措施: ipilimumab, pembrolizumab, durvalumab, idarubicin, bevacizumab (Drug)
Group 2: IT injection of double ICIs and chemodrug
Neoadjuvant therapy: intra-tumor injection of double ICIs and chemodrug.
干预措施: ipilimumab, pembrolizumab, durvalumab, idarubicin, bevacizumab (Drug)
Group 3: IT injection of double ICIs and chemodrug plus bevacizumab
Neoadjuvant therapy: intra-tumor injection of double ICIs and chemodrug plus bevacizumab.
干预措施: ipilimumab, pembrolizumab, durvalumab, idarubicin, bevacizumab (Drug)
结局指标
主要结局
pCR rate for the study groups
时间窗: Six months
Pathologic complete response (pCR) is defined as after neoadjuvant therapy, the surgical specimen can not find any residual cancer cells.
mPR rate for the study groups
时间窗: Six months
Major pathologic response (MPR) is defined as pathological less than 10% survival cancer cells after tumor resection.
次要结局
- Response rates to neoadjuvant treatment(Six years)
- Toxicity of the study groups(Six months)
- Overall survival(Six years)
- Recurrence-free survival(Six years)