Phase 1 Multiple Ascending Dose Study of XL184 Monotherapy in Japanese Subjects With Advanced or Metastatic Solid Tumors
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
- 2
- 主要终点
- Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose
研究概览
简要总结
The purpose of this study is to evaluate the safety profile, tolerability, pharmacokinetics (PK), pharmacodynamics, pharmacogenomic (PGX) and preliminary efficacy following daily oral doses of cabozantinib (XL184) in Japanese patients with advanced or metastatic solid tumors. Also, the effect of XL184 in the treatment of non-small cell lung cancer (NSCLC) patients with various activating mutations will be evaluated at the recommended Phase 2 dose.
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
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects with advanced or metastatic solid tumors for whom the standard of care is ineffective or inappropriate.
- •NSCLC expansion cohort subjects must have confirmed NSCLC (Stage IIIb or IV) and documented activating mutations.
- •At least 4 weeks must have elapsed from the last anti-cancer therapy. At least 6 weeks for nitrosoureas, mitomycin C and liposomal doxorubicin.
- •Have adequate bone marrow function, adequate liver function, and adequate renal function.
- •Sexually active subjects (men and women of child-bearing potential (WOCBP)) must agree to use medically accepted barrier methods of contraception (eg, male or female condom) during the course of the study and for 4 months after the last dose of study drug(s), even if oral contraceptives are also used. All subjects of reproductive potential must agree to use both a barrier method and a second method of birth control. Women of childbearing potential (WOCBP) must have a negative pregnancy test at screening.
排除标准
- •Symptomatic central nervous system (CNS) metastasis, or active CNS metastasis requiring medication.
- •WOCBP who are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for the entire study period and for 4 months after the last dose of investigational product.
- •Women who are pregnant or breastfeeding.
- •Sexually active fertile men not using effective birth control for the entire study period and for 4 months after the last dose of investigational product if their partners are WOCBP.
- •Subjects who have uncontrolled intercurrent illness including, but not limited to, infection requiring systemic therapy, symptomatic congestive heart failure, uncontrolled hypertension, uncontrolled angina pectoris, uncontrolled peptic ulcer, cardiac arrhythmia requiring medication.
- •Subjects who are HIV antibody positive, HBs antigen positive, and/or HCV antibody positive.
- •Subjects with body cavity fluid retention which requires drainage.
- •Subjects with any major surgery within 8 weeks prior to study enrollment.
- •Subjects with major unhealed wounds or fracture.
- •Subjects with a history or concurrent diagnosis of gastrointestinal perforation.
- •Subjects with evidence of bleeding tendency or coagulopathy.
- •Subjects with a history of thromboembolism.
- •Subjects with a history of or concurrent pancreatitis.
- •Exposure to any investigational drug within 30 days of enrollment.
- •Subjects receiving radiation therapy or treatment with radionuclides within 6 to 2 weeks before first dose of XL
- •NSCLC expansion cohorts: subjects must not be diagnosed with another malignancy within 2 years before first dose of XL184.
研究组 & 干预措施
Cabozantinib capsules and tablets
Subjects will be enrolled in cohorts at different dose levels in order to determine the maximum tolerated dose of cabozantinib. Initially, subjects enrolled will receive the capsule formulation; other subjects will receive the tablet formulation.
干预措施: cabozantinib capsules (Drug)
Cabozantinib capsules and tablets
Subjects will be enrolled in cohorts at different dose levels in order to determine the maximum tolerated dose of cabozantinib. Initially, subjects enrolled will receive the capsule formulation; other subjects will receive the tablet formulation.
干预措施: cabozantinib tablets (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose
时间窗: Assessed in the clinic on Days 1 through 29
To establish the MTD and recommended Phase 2 dose (or dose range as appropriate) of XL184 when administered orally on a once daily schedule in subjects with advanced or metastatic solid tumors.
次要结局
- Safety and tolerability of XL184(From study start to October 2014)
- Plasma Pharmacokinetics(Assessed in the clinic from Day 1 through Day 29)
- Tumor response (preliminary anti-tumor activity)(Study start to October 2014)