NCT01283516已完成1 期
A Phase I, Multi-center, Open Label Dose Escalation Study of LDK378, Administered Orally in Adult Patients With Tumors Characterized by Genetic Abnormalities in Anaplastic Lymphoma Kinase (ALK)
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 304
- 试验地点
- 7
- 主要终点
- Number of Participants With Dose Limiting Toxicities (DLTs)
研究概览
简要总结
This study assessed the safety and efficacy of LDK378 in adult patients with genetic abnormalities in anaplastic lymphoma kinase (ALK).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •ECOG Performance Status of ≤ 2 and life expectancy of ≥ 12 weeks.
- •Diagnosed with a locally advanced or metastatic malignancy that has progressed despite standard therapy, or for which no effective standard therapy exists. Only patients with tumors characterized by genetic abnormalities in ALK were enrolled.
- •For NSCLC, an ALK translocation must be detected by FISH in ≥ 15% of tumor cells.
- •In patients with diseases other than NSCLC, ALK translocation is not required and overexpression of ALK protein may be considered indicative of a genetic abnormality in ALK.
- •Patients with measurable or non-measurable disease as determined by modified RECIST version 1.0 in dose-escalation phase, and patients with at least one measurable lesion as determined by RECIST 1.0 in expansion phase.
排除标准
- •Patients with symptomatic central nervous system (CNS) metastases who were neurologically unstable or required increasing doses of steroids to control their CNS disease were excluded.
- •Patients with a prior or current history of a second malignancy, impaired GI function, history of pancreatitis or increased amylase or lipase, known diagnosis of HIV, and clinically significant cardiac disease were excluded.
- •Patients treated with chemotherapy or biologic therapy or other investigational agent < 2 weeks prior to starting study drug for compounds with a half-life ≤ 3 days, and < 4 weeks prior to starting study drug for compounds with a prolonged half-life were excluded.
- •Further, patients treated with medications that were known to be strong inhibitors or inducers of CYP3A4/5 that could not be discontinued at least a week prior to start of treatment with LDK378 and for the duration of the study were also excluded.
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
LDK378 750 mg: Arm 1A and Arm 1B
Experimental
NSCLC patients previously treated with an ALK inhibitor
干预措施: LDK378 (Drug)
LDK378 750 mg: Arm 2
Experimental
NSCLC patients not previously treated with an ALK inhibitor
干预措施: LDK378 (Drug)
LDK378 750 mg: Arm 3
Experimental
Patients with other tumors that are ALK positive other than NSCLC
干预措施: LDK378 (Drug)
结局指标
主要结局
Number of Participants With Dose Limiting Toxicities (DLTs)
时间窗: 33 months
The maximum tolerated dose (MTD) was defined as the highest dose for a given schedule that was expected to cause DLTs in no more than 33% of patients during the first cycle of treatment. A patient with multiple occurrences of a DLT under one treatment is counted only once in the AE category for that treatment. MTD was determined at 750mg.
次要结局
- Overall Response Rate Based on Blinded Independent Review Committee (BIRC) Assessment(275 weeks)
- Progression-free Survival Based on BIRC Assessment(275 weeks)
- Primary Pharmacokinetics (PK) Parameter: AUC0-24h(PK run-in of dose escalation phase, Cycle 1 Day 8 of dose escalation phase, Cycle 1, Day 1 of dose escalation phase, Cycle 2 Day 1 of dose escalation & dose expansion phases)
- Secondary Pharmacokinetics (PK) Parameter: T1/2(PK Run-in dose escalation phase)
- Duration of Response (DOR) Based on Investigator Assessment(275 weeks)
- Primary Pharmacokinetics (PK) Parameter: AUC0-last(PK run-in of Dose Escalation phase)
- Secondary Pharmacokinetics (PK) Parameter: CLss/F(Cycle 1 Day 8 of dose escalation phase, Cycle 2 Day 1 of dose escalation & dose expansion phases)
- Secondary Pharmacokinetics (PK) Parameter: Racc(Cycle 1 Day 8 of dose escalation phase, Cycle 2 Day 1 of dose escalation & dose expansion phases)
- Duration of Response (DOR) Based on BIRC(275 weeks)
- Primary Pharmacokinetics (PK) Parameter: Tmax(PK run-in of dose escalation phase, Cycle 1 Day 8 of dose escalation phase, Cycle 1, Day 1 of dose escalation phase, Cycle 2 Day 1 of dose escalation & dose expansion phases)
- Secondary Pharmacokinetics (PK) Parameter: CL/F(PK Run-in dose escalation phase)
- Overall Response Rate (ORR) Based on Investigator Assessment(275 weeks)
- Progression-free Survival Based on Investigator Assessment(275 weeks)
- Primary Pharmacokinetics (PK) Parameter: Cmax(PK run-in of dose escalation phase, Cycle 1 Day 8 of dose escalation phase, Cycle 1, Day 1 of dose escalation ion phase, Cycle 2 Day 1 of dose escalation & expansion phases)
- Secondary Pharmacokinetics (PK) Parameter: Vz/F(PK Run-in dose escalation phase)
研究者
研究点 (7)
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