A Multi-center, Randomized Open Label Study to Assess the Systemic Exposure, Effiacy, and Safety of 450 mg Ceritinib Taken With a Low-fat Meal and 600 mg Ceritinib Taken With a Low-fat Meal as Compared With That of 750 mg Ceritinib Taken in the Fasted State in Adult Patients With ALK Rearranged (ALK-positive) Metastatic Non-small Cell Lung Cancer (NSCLC)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 306
- 试验地点
- 8
- 主要终点
- Plasma concentration of ceritinib
研究概览
简要总结
A Phase I study to assess the systemic exposure, effiacy, and safety of 450 mg ceritinib taken with a low-fat meal and 600 mg ceritinib taken with a low-fat meal as compared with that of 750 mg ceritinib taken in the fasted state in adult patients with ALK rearranged (ALK-positive) metastatic non-small cell lung cancer (NSCLC)
详细描述
This was an open-label, randomized, multi-center, parallel design, Phase I study in which the systemic exposure, efficacy and safety of ceritinib administered at 450 mg or 600 mg with a low-fat meal vs 750 mg in the fasted state was assessed in subjects with ALK+ NSCLC following multiple oral daily dosing of ceritinib. Subjects were randomized in a 1:1:1 ratio to once daily doses of oral ceritinib (450 mg following a low-fat meal, 600 mg following a low-fat meal or ceritinib 750 mg administered on an empty stomach). Randomization was stratified by brain metastases at Screening (presence or absence) and by prior treatment (prior crizotinib use with ALK+ determined by Fluorescent in situ hybridization (FISH); crizotinib-naïve but could be previously treated with other systemic anti-cancer therapy with ALK+ determined by FISH, or treatment-naïve subjects with ALK+ by IHC).
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Histologically or cytologically confirmed diagnosis of stage IIIB (and is not a candidate for definitive multimodality therapy) or IV ALK-positive NSCLC.
- •Patients may have received one prior treatment regimen with crizotinib (all other ALK inhibitors are excluded).
- •Patients may have received prior chemotherapy, biologic therapy, or other investigational agents. ALK inhibitors other than crizotinib are excluded.
- •Patient has a World Health Organization (WHO) performance status 0-2.
排除标准
- •Prior treatment with an ALK inhibitor other than crizotinib.
- •History of carcinomatous meningitis.
- •Presence or history of a malignant disease other than an ALK-positive advanced tumor that has been diagnosed and/or required therapy within the past 3 years.
- •Clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months)
- •Patient has history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis (i.e., affecting activities of daily living or requiring therapeutic intervention).
- •Patient has other severe, acute, or chronic medical conditions
- •Patient is currently receiving treatment with warfarin sodium (Coumadin®) or any other coumarin-derivative anticoagulants.
研究组 & 干预措施
ceritinib 450 mg with a low-fat meal
Oral ceritinib QD (21 days/ cycle) at a dose of 450 mg (3×150 mg/capsule) administered in the morning immediately (within 30 minutes)following a low-fat meal.
干预措施: ceritinib (Drug)
ceritinib 600 mg with a low-fat meal
Oral ceritinib QD (21 days/ cycle) at a dose of 600 mg (4×150 mg/capsule) administered in the morning immediately (within 30 minutes) following a low-fat meal.
干预措施: ceritinib (Drug)
ceritinib 750 mg on an empty stomach
Oral ceritinib QD (21 days/ cycle) at a dose of 750 mg (5×150 mg/capsule) administered in the morning on an empty stomach (i.e., fasted from food and drink except water)
干预措施: ceritinib (Drug)
结局指标
主要结局
Plasma concentration of ceritinib
时间窗: Study Day 22
Pharmacokinetics (PK) parameters, including but not limited to AUClast, AUC0-24h, Cmax, Tmax, Tlast, Racc, and CLss/F
次要结局
- Plasma concentration of ceritinib(Study Day 1)
- Objective response rate (ORR)(Tumor assessments every 6 weeks until cycle 9. At least every 12 weeks thereafter until progressive disease.)
- Safety profile(The primary analysis will be based on data from all patients, up to the time at which all randomized patients have completed at least 12 weeks of ceritinib treatment or have discontinued study treatment, whichever is earlier.)
- Duration of response (DOR)(Tumor assessments every 6 weeks until cycle 9. At least every 12 weeks thereafter until progressive disease.)