A Phase 3, Randomized, Controlled, Multi-Center, Open-Label Study to Compare Tivozanib Hydrochloride to Sorafenib in Subjects With Refractory Advanced Renal Cell Carcinoma
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 350
- 试验地点
- 185
- 主要终点
- Progression-free Survival (PFS)
研究概览
简要总结
This is a Phase 3, open-label, randomized, controlled, multi-national, multi-center, parallel-arm study comparing tivozanib to sorafenib in participants with refractory advanced renal cell carcinoma (RCC).
Participants will be randomized (1:1) to treatment with tivozanib or sorafenib.
Participants will be stratified by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk category (favorable; intermediate; poor) and prior therapy (two prior vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKI); a prior checkpoint inhibitor [programmed cell death -1 protein (PD-1) or PD-1 ligand (PD1-L) inhibitor] plus a prior VEGFR TKI; a prior VEGFR TKI plus any other systemic agent).
All participants will be evaluated for progression free survival, overall survival, objective response rate, and the duration of response as well as safety and tolerability.
Pharmacokinetic (PK) analyses are also included in study.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18 years or older
- •Participants with metastatic RCC who have failed 2 or 3 prior systemic regimens, one of which includes a VEGFR TKI other than sorafenib or tivozanib.
- •Histologically or cytologically confirmed RCC with a clear cell component (participants with pure papillary cell tumor or other non-clear cell histologies, including collecting duct, medullary, chromophobe, and unclassified RCC are excluded).
- •Measurable disease per the Response Evaluation Criteria in Solid Tumors (RECIST) criteria Version 1.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Life expectancy ≥ 3 months.
排除标准
- •Prior treatment with sorafenib or tivozanib.
- •More than 3 prior regimens for metastatic RCC.
- •Known central nervous system (CNS) metastases other than stable, treated brain metastases. Participants with previously treated brain metastasis will be allowed if the brain metastasis has been stable by neuroimaging without steroid treatment for at least 3 months following prior treatment (radiotherapy or surgery).
- •Significant hematologic, gastrointestinal, thromboembolic, vascular, bleeding, or coagulation disorders.
- •Significant serum chemistry abnormalities
- •Significant cardiovascular disease, including: Active clinically symptomatic left ventricular failure, uncontrolled hypertension, myocardial infarction, severe angina, or unstable angina within 6 months prior to administration of first dose of study drug, history of serious ventricular arrhythmia, cardiac arrhythmias requiring anti-arrhythmic medications.
- •Inadequate recovery from any prior surgical procedure or major surgical procedure within 4 weeks prior to administration of first dose of study drug.
- •Currently active second primary malignancy.
研究组 & 干预措施
Tivozanib hydrochloride
Participants randomized to this arm will receive the study drug, tivozanib hydrochloride.
干预措施: Tivozanib hydrochloride (Drug)
Sorafenib
Participants randomized to this arm will receive the comparator drug, sorafenib.
干预措施: Sorafenib (Drug)
结局指标
主要结局
Progression-free Survival (PFS)
时间窗: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first. Disease progression was assessed every 8 weeks (up to approximately 5 years)
The PFS, as assessed by a blinded independent radiological review (IRR), is defined as the time from randomization to first documentation of objective tumor progression (progressive disease) or death due to any reasons whichever comes first. Disease progression per RECIST 1.1 criteria is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
次要结局
- Objective Response Rate (ORR)(Every 8 weeks from date of randomization until disease progression (up to approximately 5 years))
- Duration of Response (DOR)(Assessed every 8 weeks from date of randomization until date of progression (up to approximately 5 years))
- Overall Survival (OS)(Date of randomization to date of death (up to approximately 5 years))