Phase II Single-Arm Study of Durvalumab and Bevacizumab Following Transarterial Radioembolization Using Yttrium-90 Glass Microspheres (TheraSphere™) in Unresectable Hepatocellular Carcinoma Amenable to Locoregional Therapy
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 58
- 试验地点
- 22
- 主要终点
- Progression Free Survival (PFS)
研究概览
简要总结
The purpose of this study is to measure the efficacy and safety of durvalumab intravenous (IV) solution plus bevacizumab IV solution after transarterial radioembolization (Yttrium 90 glass microspheres TARE) in participants with unresectable hepatocellular carcinoma (HCC) amenable to embolization.
详细描述
A Phase II single-arm study conducted in participants with unresectable Hepatocellular carcinoma (HCC) eligible for embolization and not eligible for or who have declined treatment with resection and/or ablation or liver transplant.
Participants with previous Transarterial Chemoembolization (TACE) or TARE associated with the curative setting are permitted with a 6-month washout.
Approximately 120 participants with unresectable but amenable to locoregional therapy HCC eligible for embolization will be screened in the study at approximately 20 sites in the US to enroll approximately 60 participants.
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
- 18 Years 至 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants with confirmed unresectable HCC
- •Participants with Lung dose threshold for Yttrium 90 glass microspheres of 30 Gy (equal or less than 30 Gy per treatment for glass) and an estimated Future liver remnant volume (FLRV) ≥ 30% of whole liver volume.
- •Participants with more than 1 prior embolization are permitted if more than 12 months ago, for a different primary lesion, and FLR > 30%.
- •Participants with no evidence of extrahepatic disease on any available imaging
- •Participants with one or more measurable lesions, unilobar disease for participants with segmental or right anterior/posterior portal vein invasion (Vp1/Vp2) and eligible for Yttrium 90 glass microspheres TARE.
- •Participants having Child-Pugh score class A.
- •Participants having ECOG performance status of 0 or 1 at enrollment
- •Adequate organ and marrow function
排除标准
- •Disease amenable to curative surgery, ablation or transplantation. Transplant patients are considered eligible if outside of Milan criteria and not currently listed for transplant.
- •Participants co-infected with HBV and HDV
- •Any history of nephrotic or nephritic syndrome.
- •Clinically significant (eg, active) cardiovascular disease
- •Participants with uncontrolled hypertension
- •History of hepatic encephalopathy
- •Known hereditary predisposition to bleeding or thrombosis; any prior or current evidence of bleeding diathesis.
- •Receipt of more than 1 prior embolization (TACE or TARE) treatment/procedure
- •Participant has received any prior anticancer systemic therapy for unresectable HCC.
- •History of arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to enrollment.
- •History of abdominal fistula or gastrointestinal (GI) perforation, non-healed gastric ulcer that is refractory to treatment, or active GI bleeding within 6 months prior to enrollment
研究组 & 干预措施
Yttrium 90 glass microspheres TARE in combination with Durvalumab and Bevacizumab
Participants will undergo Yttrium 90 glass microspheres TARE according to the dosimetry recommendation.
干预措施: Transarterial Radioembolization (TARE) (Procedure)
Yttrium 90 glass microspheres TARE in combination with Durvalumab and Bevacizumab
Participants will undergo Yttrium 90 glass microspheres TARE according to the dosimetry recommendation.
干预措施: Bevacizumab (Drug)
Yttrium 90 glass microspheres TARE in combination with Durvalumab and Bevacizumab
Participants will undergo Yttrium 90 glass microspheres TARE according to the dosimetry recommendation.
干预措施: Durvalumab (Drug)
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: From Day 1 until date of progressive disease or death [Approximately 3 years]
PFS is defined as the time from Day 1 (day of TARE) until the date of progressive disease per modified Response Evaluation Criteria in Solid Tumors (mRECIST), as assessed by the investigator, or death due to any cause. It is measured to assess the efficacy of TARE followed by durvalumab monotherapy followed by durvalumab + bevacizumab in participants with unresectable HCC amenable to locoregional therapy.
次要结局
- Duration of Response (DoR)(Time from first documented response until documented progression (Approximately 3 years))
- Overall Survival (OS)(Day 1 to 18 months or until death (Approximately 3 years))
- Number of participants with Adverse events (AEs)(From Screening (Day -28 to Day 1) until 90 days after the last dose of study drug)
- Objective Response Rate (ORR)(From Day 1 until progression, or the last evaluable assessment in the absence of progression (Approximately 3 years))
- Number of participants with Adverse events (AEs)(From Screening (Day -28 to Day 1) until 90 days after the last dose of study drug)
- Objective Response Rate (ORR)(From Day 1 until progression, or the last evaluable assessment in the absence of progression (Approximately 3 years))
- Overall Survival (OS)(Day 1 to 18 months or until death (Approximately 3 years))
- Duration of Response (DoR)(Time from first documented response until documented progression (Approximately 3 years))