Phase IIA Single-Arm Study of Treatment of Patients With Advanced Liver Cancer With a Combination of TATE (Transarterial Tirapazamine Embolization) Followed by an Anti-PD-1 Monoclonal Antibody
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 54
- 试验地点
- 4
- 主要终点
- Overall Response Rate
研究概览
简要总结
This is a multi-center, open-label phase IIA study that investigates the preliminary efficacy of Trans-arterial Tirapazamine Embolization (TATE) treatment of liver cancer followed by a PD-1 checkpoint inhibitor (nivolumab). Patients with two types of cancers will be enrolled, advanced hepatocellular carcinoma (HCC),and metastatic gastric cancer. All enrolled patients need to have liver lesions and have progressed on a prior immune checkpoint inhibitor.
详细描述
The goal of the study is to investigate whether tumor necrosis induced by Trans-arterial Tirapazamine Embolization (TATE) treatment can boost anti-tumor immunity and enhance the therapeutic efficacy of immune checkpoint inhibitor. Patients with advanced liver cancers (primary HCC or metastatic gastric cancer) who have progressed on a prior immune checkpoint inhibitor will be enrolled in the study. Liver lesions will be treated with up to 4 TATE treatments for optimal debulking, which also serve as a vaccination process toward tumor. Lesion not treated with TATE will be used for monitoring the response toward a PD-1 inhibitor (Nivolumab) for abscopal effect. If a patient subsequently develops an "escape" to the PD-1 inhibitor, patient can have another 2 TATE treatments of the escaped tumor lesion. Dosing of the PD-1 inhibitor is per standard FDA-approved dosing schedule and continues until progressive disease. The efficacy will be assessed by the response rate (RR) using RECIST.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with a confirmed diagnosis of (1) advanced HCC or (2) metastatic gastric cancer.
- •Patients between ages 18 and 80
- •If HCC patients, they should have progressive disease (PD) on an immune therapy for advanced HCC. For patients with metastatic gastric cancer, they should have failed at least one line of systemic chemotherapy and an immune checkpoint inhibitor.
- •Patients with liver tumor lesions with at least one with a diameter of 2 cm or bigger, which is amendable for (super-)selective TATE as the target lesion.
- •ECOG score 2 or less
- •Child-Pugh scores 5-7 for HCC patients
- •All prior chemotherapy at least 4 weeks prior to study treatment. Immunotherapy not subject to this limitation.
- •No major GI bleeding in the prior 2 months.
- •8. Hgb>=8, platelet >= 50,000, Cr =< 2, AST and ALT < 10 X ULN, t-Bilirubin < 3,
- •Patients with a history of major autoimmune disorders excluded.
排除标准
- 未提供
研究组 & 干预措施
Metastatic Gastro-esophageal cancer
PD-1 inhibitor (Nivolumab 360 mg Q3W IV) starts at day 1, and continues until progression.
TATE treatment starts at day 8 for debulking up to 4 cycles. If escape lesion appears, two more TATE treatments can be given. Tirapazamine dose at 35 mg flat dose given before embolization.
干预措施: Nivolumab Injectable Product (Drug)
Advanced Hepatocellular carcinoma
PD-1 inhibitor (Nivolumab 360 mg Q3W IV ) starts at day 1, and continues until progression.
TATE treatment starts at day 8 for debulking up to 4 cycles. If escape lesion appears, two more TATE treatments can be given. Tirapazamine dose at 35 mg flat dose given before embolization.
干预措施: Trans-arterial tirapazamine embolization (Combination Product)
Metastatic Gastro-esophageal cancer
PD-1 inhibitor (Nivolumab 360 mg Q3W IV) starts at day 1, and continues until progression.
TATE treatment starts at day 8 for debulking up to 4 cycles. If escape lesion appears, two more TATE treatments can be given. Tirapazamine dose at 35 mg flat dose given before embolization.
干预措施: Trans-arterial tirapazamine embolization (Combination Product)
Advanced Hepatocellular carcinoma
PD-1 inhibitor (Nivolumab 360 mg Q3W IV ) starts at day 1, and continues until progression.
TATE treatment starts at day 8 for debulking up to 4 cycles. If escape lesion appears, two more TATE treatments can be given. Tirapazamine dose at 35 mg flat dose given before embolization.
干预措施: Nivolumab Injectable Product (Drug)
结局指标
主要结局
Overall Response Rate
时间窗: up to 24 months
Per RECIST 1.1 criteria
次要结局
- Overall survival(through study completion, an average of 3 years)
- Duration of Response(up to 24 months)
- Time to Progression(up to 24 months)
- Progression Free Survival(up to 24 months)