A Phase 1, Open-Label, Non-Randomized, Dose-Escalating Safety, Tolerability and Pharmacokinetic Study of TAS-119 in Combination With Paclitaxel in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 30
- 试验地点
- 4
- 主要终点
- Safety and tolerability of TAS-119 in combination with paclitaxel
研究概览
简要总结
The purpose of this study is to determine the safety of TAS-119 and determine the most appropriate dose in combination with Paclitaxel for subsequent studies in patients with advanced solid tumors.
TAS-119 is a novel, selective Aurora A kinase inhibitor, which has previously been demonstrated to enhance the activity of paclitaxel in preclinical studies
详细描述
Background and rationale for study:
In nonclinical pharmacology studies TAS-119 significantly enhanced the antitumor activity of the microtubule stabilizer paclitaxel and TAS-119 is being developed for use in combination with paclitaxel.
TAS-119 selectively inhibits the kinase inhibitor Aurora A. AurA regulates cell division by controlling the transition from G2 to M phase. Overexpression of AurA is associated with resistance to taxanes.
The study will be conducted in two sequential phases:
Dose Escalation Phase with the purpose to determine the maximum tolerated dose and the recommended Phase 2 dose of TAS-119 given in combination with paclitaxel
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
- •Is a male or female ≥ 18 years of age, that has provided written informed consent.
- •Has histologically or cytologically confirmed advanced, unresectable metastatic solid tumor(s) for which the patients have no available therapy likely to provide clinical benefit, or for which paclitaxel is considered a standard of care.
- •Has adequate organ function as defined by the following criteria:
- •Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 3.0 × upper limit of normal (ULN); if liver function abnormalities are due to underlying liver metastasis, AST (SGOT) and ALT (SGPT) ≤ 5 × ULN.
- •Total serum bilirubin ≤ 1.5 × ULN.
- •Absolute neutrophil count ≥ 1,500/mm3 (excluding measurements obtained within 7 days after administration of granulocyte colony-stimulating factor [G-CSF]).
- •Platelet count ≥ 100,000/mm3 (IU: ≥ 100 × 109/L) (excluding measurements obtained within 7 days after a transfusion of platelets).
- •Hemoglobin ≥ 9.0 g/dL
- •Total serum creatinine ≤ 1.5 × ULN
- •Serum albumin ≥ 3.0 mg/dL.
排除标准
- •Previous inability to tolerate any dose of paclitaxel (i.e., the subject required a paclitaxel dose reduction or discontinuation).
- •Has received any treatments prohibited in this trial within specified time frames
- •Has a serious illness or medical condition(s) that would affect safety or tolerability of the study treatments
- •Has history of Grade 2 or greater peripheral neuropathy during the 3 months prior to enrollment.
- •Has known hypersensitivity to TAS-119 or its components.
- •Has known hypersensitivity to Cremophor® EL, paclitaxel or its components.
- •Is a pregnant or lactating female.
研究组 & 干预措施
TAS-119
TAS-119 tablets, oral, dose-escalating, 28-day cycle.
Paclitaxel (90mg/m2) is administered IV in combination with TAS-119 in each of the arms.
干预措施: TAS-119 (Drug)
TAS-119
TAS-119 tablets, oral, dose-escalating, 28-day cycle.
Paclitaxel (90mg/m2) is administered IV in combination with TAS-119 in each of the arms.
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Safety and tolerability of TAS-119 in combination with paclitaxel
时间窗: Safety monitoring will begin at the time of the first dose of TAS-119, and will continue until all patients are discontinued from treatment or until 12 months from the last patient enrolled (up to 3 years).
Standard safety monitoring and grading using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 will be used. The safety and tolerability of TAS-119 will be evaluated by the number and severity of adverse events, vital signs, physical exam, and clinical laboratory assessments.
次要结局
- Overall response according to RECIST guidelines (version 1.1, 2009)(Computed tomography (CT) scans for tumor imaging will be performed at the end of every 2 treatment cycles (8 weeks) and an average of 4 cycles (16 weeks))