A Phase 1 Study of the Oral TRK Inhibitor Larotrectinib in Adult Patients With Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 75
- 试验地点
- 8
- 主要终点
- Number of participants with adverse events
研究概览
简要总结
This research study is done to test the safety of the drug larotrectinib in adult cancer patients. The drug may be used to treat cancer with a change in a particular gene (NTRK1, NTRK2 or NTRK3), because it blocks the action of these genes in cancer cells. The study also investigates how the drug is absorbed and processed in the human body. This is the first study to test larotrectinib in humans with cancer, for whom no other effective therapy exists.
详细描述
The trial will be conducted in 2 parts: an initial dose escalation phase of larotrectinib in subjects with advanced solid tumors will be followed by an expansion phase in subjects with solid tumors having a NTRK fusion.
The objectives of the study are to determine the safety, pharmacokinetic profile, recommended dose and efficacy of orally administered larotrectinib in patients with NTRK fusions.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 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
- •Adult patients with a locally advanced or metastatic solid tumor that has progressed or was nonresponsive to available therapies, are unfit for standard chemotherapy or for which no standard or available curative therapy exists
- •Proof of a malignancy harboring a NTRK fusion
- •Eastern Cooperative Oncology Group (ECOG) score of 0, 1 or 2 and a life expectancy of at least 3 months
- •Adequate hematologic, hepatic, and renal function
排除标准
- •Patients with unstable primary central-nervous-system tumors or metastasis, exceptions possible
- •Clinically significant active cardiovascular disease or history of myocardial infarction
- •Active uncontrolled systemic bacterial, viral, or fungal infection
- •Current treatment with a strong CYP3A4 inhibitor or inducer
- •Pregnancy or lactation
研究组 & 干预措施
Tumor patients_Dose 1
Adult patients with solid tumors receiving 50 mg of BAY2757556 once daily (dose escalation cohort).
干预措施: Larotrectinib (Vitrakvi, BAY2757556) (Drug)
Tumor patients_Dose 2
Adult patients with solid tumors receiving 100 mg of BAY2757556 once daily (dose escalation cohort).
干预措施: Larotrectinib (Vitrakvi, BAY2757556) (Drug)
Tumor patients_Dose 3
Adult patients with solid tumors receiving 100 mg of BAY2757556 twice daily (dose escalation cohort).
干预措施: Larotrectinib (Vitrakvi, BAY2757556) (Drug)
Tumor patients_Dose 4
Adult patients with solid tumors receiving 200 mg of BAY2757556 once daily (dose escalation cohort).
干预措施: Larotrectinib (Vitrakvi, BAY2757556) (Drug)
Tumor patients_Dose 5
Adult patients with solid tumors receiving 150 mg of BAY2757556 twice daily (dose escalation cohort).
干预措施: Larotrectinib (Vitrakvi, BAY2757556) (Drug)
Tumor patients_Dose 6
Adult patients with solid tumors receiving 200 mg of BAY2757556 twice daily (dose escalation cohort).
干预措施: Larotrectinib (Vitrakvi, BAY2757556) (Drug)
Tumor patients_Expansion
Adults patients with solid tumors and neurotrophic tyrosine kinase (NTRK) genes or proteins of types 1 - 3 (dose expansion cohort).
Patients receive either the recommended or maximum tolerated dose of BAY2757556 as determined in the dose escalation part.
干预措施: Larotrectinib (Vitrakvi, BAY2757556) (Drug)
结局指标
主要结局
Number of participants with adverse events
时间窗: 25 months
Severity of adverse events
时间窗: 25 months
The severity of adverse events will be assesssed according to the NCI CTCAE version 4.03.
Maximum tolerated dose (MTD)
时间窗: 25 months
Recommended dose for dose expansion
时间窗: 25 months
次要结局
- Maximum concentration of larotrectinib in plasma (Cmax)(Predose and 0.25, 0.5, 1, 2, 4, 6 and 8 hours after drug administration on Days 1 and 8 of Cycle 1)
- Overall Response Rate (ORR)(Up to 60 months)
- Time to maximum concentration of larotrectinib in plasma (Tmax)(Predose and 0.25, 0.5, 1, 2, 4, 6 and 8 hours after drug administration on Days 1 and 8 of Cycle 1)
- Half-life of larotrectinib in plasma (t1/2)(Predose and 0.25, 0.5, 1, 2, 4, 6 and 8 hours after drug administration on Days 1 and 8 of Cycle 1)
- Area under the concentration versus time curve of larotrectinib in plasma (AUC)(Predose and 0.25, 0.5, 1, 2, 4, 6 and 8 hours after drug administration on Days 1 and 8 of Cycle 1)
- Duration of Response (DOR)(Up to 60 months)