A Phase 1 Dose-Escalation Study of the Safety and Pharmacokinetics of XL184 Administered Orally to Subjects With Advanced Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Exelixis
- 入组人数
- 85
- 试验地点
- 5
- 主要终点
- Safety, tolerability, maximum tolerated dose (MTD), and dose-limiting toxicity of oral administration of XL184
研究概览
简要总结
The purpose of this study is to determine the best and safest dose of XL184 administered orally. XL184 is a new chemical entity that inhibits VEGFR2, MET and RET, kinases implicated in tumor formation, growth and migration. To determine the highest safe dose, subjects will receive different amounts of the drug. The first group of subjects will receive the lowest dose of XL184. As long as no medically unacceptable side effects are noted, the dose will be increased for the next group. When the maximum tolerated dose (MTD) is reached, at least 20 subjects with Medullary Thyroid Cancer (MTC) will be enrolled to evaluate the effect of XL184 in this population.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed advanced malignancy (solid tumor or lymphoma) that is metastatic or unresectable for which standard curative measures do not exist or are no longer effective
- •Eastern Cooperative Oncology Group (ECOG) performance status </= 2
- •Life expectancy greater than 3 months
- •Adequate organ and marrow function
- •Written informed consent
- •Use of acceptable methods of contraception during the course of the study and for 3 months after completion of study
- •In the MTD expanded cohort: at least 20 subjects with metastatic and/or advanced/locally recurrent Medullary Thyroid Cancer not appropriate for surgical resection with measurable disease as defined by RECIST
排除标准
- •Chemotherapy, immunotherapy or radiation within 4 weeks (or nitrosoureas or mitomycin C within 6 weeks) before the first scheduled dose of XL184
- •Administration of an investigational drug within 30 days of the first dose of XL184
- •Subject has not recovered from adverse events due to investigational agents or other medications administered more than 4 weeks before study enrollment
- •Known brain metastases
- •Uncontrolled intercurrent illness
- •Pregnancy or breastfeeding
- •Known HIV positive
- •Known allergy or hypersensitivity to any of the components of the XL184 formulation
研究组 & 干预措施
1
干预措施: XL184 (Drug)
结局指标
主要结局
Safety, tolerability, maximum tolerated dose (MTD), and dose-limiting toxicity of oral administration of XL184
时间窗: Assessed during periodic visits
Evaluate plasma pharmacokinetics and estimate renal elimination of oral administration of XL184
时间窗: Assessed during periodic visits
次要结局
- Long-term safety/tolerability of XL184 after oral administration for up to 1 year(Assessed during periodic visits)
- Evaluate preliminary tumor response after repeated XL184 administration(Assessed during periodic visits)
- In MTD expanded cohort: Progression-free survival and duration of response in subjects with advanced or recurrent medullary thyroid cancer(Assessed during periodic visits)