A Phase I/IIa, Single-arm, Open-label, IIT for Safety and Efficacy Evaluation of Tremelimumab Plus Durvalumab(MEDI4736) in Combination With Concurrent Transarterial Chemoembolization in Unresectable Hepatocellular Carcinoma
概览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- Yoon Jun Kim
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- PFS
概览
简要总结
Safety and Efficacy Evaluation of Tremelimumab Plus Durvalumab(MEDI4736) in Combination with Concurrent Transarterial Chemoembolization in Unresectable Hepatocellular carcinoma
详细描述
The purpose of this clinical trial is to evaluate the safety and efficacy of tremelimumab + durvalumab administered concurrently with transarterial chemoembolization (TACE) in patients diagnosed with hepatocellular carcinoma (HCC) who are not eligible for curative liver resection.
Primary Objective:
The primary objective of this clinical trial is to evaluate progression-free survival (PFS) from the time of registration using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Secondary Objectives:
Overall Survival (OS):
To assess the overall survival from the first dose of the study drug until the data cutoff point, as determined by the investigator.
Objective Response Rate (ORR):
To assess the objective response rate of target and non-target lesions using mRECIST and RECIST 1.1. Evaluations will occur every 8 weeks after 12 weeks and for the first 48 weeks from the time of registration, and then every 12 weeks thereafter.
Time to Progression (TTP):
To measure the time from registration to disease progression using mRECIST and RECIST 1.1.
Safety Evaluation:
To evaluate the safety of tremelimumab and durvalumab, including adverse events, vital signs (blood pressure and pulse rate), and laboratory safety assessments (clinical chemistry, hematology, etc.), by assessing changes from baseline.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
- •Male or female, aged ≥19 years at time of study entry.
- •Diagnosed with unequivocal HCC confirmed histologically or diagnosed radiologically according to American Association for the Study of Liver Diseases practice guideline.
- •Barcelona clinic liver cancer (BCLC) staging intermediate (B) stage or BCLC advanced stage (C) HCC with or without minimal extrahepatic disease (single-organ metastasis, ≤5 metastatic lesions).
- •Must have at least 1 untreated measurable disease (untreated target lesion i.e. a viable lesion that has never been treated with locoregional treatment \[transarterial chemoembolization {TACE}, TARE, percutaneous ethanol injection therapy, or radiofrequency ablation\]).
- •Child-Pugh score 5 or 6 points (Child-Pugh class A).
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Life expectancy of ≥ 12 weeks.
- •Body weight \>30 kg.
- •Adequate normal organ and marrow function as defined below:
排除标准
- •Eligible for potentially curative treatment (surgical resection, radiofrequency ablation or immediate liver transplantation).
- •Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti- Cytotoxic T-lymphocyte- associated antigen-4 (anti-CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune pathways, including prior randomization or treatment in a previous durvalumab and/or tremelimumab clinical study regardless of treatment arm assignment.
- •History of organ transplantation or hematopoietic stem cell transplantation.
- •Any other concurrent malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, papillary thyroid cancer, early gastric cancer, or other cancer for which the patient has been disease-free for at least five years.
- •A history of a severe contrast allergy (i.e. anaphylaxis) not controlled with premedication.
- •Any condition that, in the opinion of the Investigator, would interfere with evaluation of the investigational product (IP) or interpretation of patient safety or study results.
- •Participation in another clinical study with an IP during the last 8 weeks or 5 half-lives of the study drug, whichever is longer, prior to screening.
- •Concurrent enrolment in another clinical study, unless it is an observational (non- interventional) clinical study or during the follow-up period of an interventional study.
- •Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies) ≤1 cycle length or 14 days, whichever is longer, prior to the first dose of study drug. If sufficient wash-out time has not occurred due to the schedule or PK properties of an agent, a longer wash-out period will be required, as determined by the Investigator.
- •Any unresolved toxicity NCI-CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.
研究组 & 干预措施
Tremelimumab Plus Durvalumab (MEDI4736) in Combination with Concurrent Transarterial Chemoembolizati
After the intravenous (IV) administration of 300 mg of tremelimumab and 1,500 mg of durvalumab, transarterial chemoembolization (TACE) will be performed in combination with 1,500 mg of durvalumab via IV infusion every 4 weeks (Q4W) until disease progression (PD) is confirmed. TACE will be carried out 1 to 2 weeks (7 to 14 days) after the administration of tremelimumab + durvalumab, and thereafter, it will be performed as needed at the discretion of the investigator during the treatment period. If additional TACE is performed, there must be at least a 1-week interval between the additional TACE and the administration of durvalumab.
干预措施: Tremelimumab Plus Durvalumab (MEDI4736) (Drug)
Tremelimumab Plus Durvalumab (MEDI4736) in Combination with Concurrent Transarterial Chemoembolizati
After the intravenous (IV) administration of 300 mg of tremelimumab and 1,500 mg of durvalumab, transarterial chemoembolization (TACE) will be performed in combination with 1,500 mg of durvalumab via IV infusion every 4 weeks (Q4W) until disease progression (PD) is confirmed. TACE will be carried out 1 to 2 weeks (7 to 14 days) after the administration of tremelimumab + durvalumab, and thereafter, it will be performed as needed at the discretion of the investigator during the treatment period. If additional TACE is performed, there must be at least a 1-week interval between the additional TACE and the administration of durvalumab.
干预措施: Transarterial chemoembolization (TACE) (Procedure)
结局指标
主要结局
PFS
时间窗: the time from the first study treatment administration until the date of objective disease progression
The primary endpoint for evaluating progression-free survival (PFS) will be assessed through RECIST 1.1 evaluation.
次要结局
- OS(the time from the first study treatment administration until death due to any cause, regardless of whether the patient withdraws from therapy or receives another anticancer therapy.)
- ORR(From date of enrollment until the date of first documented progression, assessed every 8 weeks up to 12 months.)
- TTP(the time from the first study treatment administration until the first confirmed tumor progression (PD) based on the RECIST 1.1 assessment.)
- Safety of durvalumab and tremelimumab in terms of the occurrence of adverse events(Until 30 days after TACE or the last dose of tremelimumab and/or durvalumab)
研究者
Yoon Jun Kim
Coordinating Investigator
Seoul National University Hospital