A Phase 3, Randomized, Controlled Study of Cabozantinib (XL184) vs Everolimus in Subjects With Metastatic Renal Cell Carcinoma That Has Progressed After Prior VEGFR Tyrosine Kinase Inhibitor Therapy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Exelixis
- 入组人数
- 658
- 主要终点
- Progression-free Survival (PFS)
研究概览
简要总结
The purpose of this study is to evaluate the effect of Cabozantinib (XL184) compared with Everolimus (Afinitor) on progression-free survival (PFS) and overall survival (OS) in subjects with advanced renal cell cancer that has progressed after prior VEGFR tyrosine kinase inhibitor therapy.
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
- •Documented histological or cytological diagnosis of renal cell cancer with a clear-cell component.
- •Measurable disease as determined by the investigator.
- •Must have received at least one VEGFR-targeting TKI (eg, sorafenib, sunitinib, axitinib, pazopanib or tivozanib).
- •Recovery from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.
- •Adequate organ and marrow function.
- •Sexually active fertile subjects(male and female)must agree to use medically accepted methods of contraception during the course of the study and for 4 months after the last dose of study treatment.
- •Female subjects of childbearing potential must not be pregnant at screening.
排除标准
- •Prior treatment with everolimus, or any other specific or selective TORC1/PI3K/AKT inhibitor (eg, temsirolimus), or cabozantinib.
- •Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before randomization.
- •Receipt of any type of anticancer antibody (including investigational antibody) within 4 weeks before randomization.
- •Radiation therapy for bone metastasis within 2 weeks, any other external radiation therapy within 4 weeks before randomization. Systemic treatment with radionuclides within 6 weeks before randomization. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
- •Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery and stable for at least 3 months before randomization.
- •Concomitant anticoagulation at therapeutic doses with oral anticoagulants or platelet inhibitors.
- •Chronic treatment with corticosteroids or other immunosuppressive agents.
- •Serious illness other than cancer.
- •Major surgery within 3 months before randomization. Complete wound healing from major surgery must have occurred 1 month before randomization and from minor surgery at least 10 days before randomization.
- •Pregnant or lactating females.
- •Diagnosis of another malignancy within 2 years before randomization, except for superficial skin cancers, or localized, low grade tumors.
研究组 & 干预措施
Cabozantinib (XL184)
Cabozantinib (XL184) 60 mg tablet once daily.
干预措施: Cabozantinib tablets (Drug)
Everolimus (Afinitor)
Everolimus (Afinitor) 10 mg tablet once daily.
干预措施: Everolimus (Afinitor) tablets (Drug)
结局指标
主要结局
Progression-free Survival (PFS)
时间窗: PFS is measured from the date of randomization until the date of first documented disease progression or date of death from any cause as determined by the Independent Radiology Committee (IRC) per RECIST 1.1, assessed for up to 17 months.
The primary analysis of PFS is the time from randomization to date of first documented tumor progression as determined by investigator (per RECIST 1.1 criteria) or death due to any cause, whichever occurred first. A Kaplan-Meier analysis was performed to estimate the median duration.
次要结局
- Overall Survival (OS)(OS was measured from the time of randomization until 320 deaths, approximately 28 months)
- Objective Response Rate (ORR)(ORR was assessed at 8 weeks post-randomization, every 8 weeks for 12 months, and every 12 weeks until date of disease progression or death, up to May 2015 (approximately 21 months))