A Phase I, Randomized, Open-label, Multi-center, Two Period Crossover Study to Investigate the Effect of Food on the Pharmacokinetics of a Single Oral Dose of RO5185426, Followed by Administration of 960 mg RO5185426 Twice Daily to BRAF V600E Positive Metastatic Melanoma Patients
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 主要终点
- Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC [0-inf]) in the Fasted and Fed States
研究概览
简要总结
This randomized, open-label, two period crossover study will evaluate the effect of food on the pharmacokinetics of a single dose of RO5185426 and the efficacy and safety of continuous administration in patients with BRAF V600E mutation-positive metastatic melanoma. Patients will be randomized to receive in a crossover design single oral doses of RO5185426 with or without food, with a 10-day washout period between doses. Following the crossover periods, patients will receive RO5185426 orally twice daily on a continuous basis until disease progression or unacceptable toxicity occurs.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 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, >/= 18 years of age
- •Histologically confirmed metastatic melanoma (Stage IV, American Joint Committee on Cancer)
- •Positive BRAF V600E mutation result determined by Cobas 4800 BRAF V600 Mutation Test
- •Previously treated patients must have failed at least one prior treatment regimen; if patients have received prior systemic treatments for metastatic melanoma, the time elapsed from previous therapy must be >/= 28 days; patients must have recovered fully from toxicities of all prior therapy
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- •Evaluable disease (measurable for disease progression according to RECIST criteria)
- •Adequate hematological, renal and liver function
排除标准
- •Active CNS lesions
- •History of or known spinal cord compression or carcinomatous meningitis
- •Anticipated or ongoing administration of anti-cancer therapies other than those administered in this study
- •Previous malignancy within the past 5 years except for basal or squamous cell carcinoma of the skin, melanoma in-situ and carcinoma in-situ of the cervix
- •Previous treatment with BRAF inhibitor (sorafenib allowed) or MEK inhibitor
- •Refractory nausea or vomiting, malabsorption, external biliary shunt, or history of any type of gastrointestinal surgery that would preclude adequate absorption of study drug
研究组 & 干预措施
1
干预措施: RO5185426 (Drug)
2
干预措施: RO5185426 (Drug)
C
干预措施: RO5185426 (Drug)
结局指标
主要结局
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC [0-inf]) in the Fasted and Fed States
时间窗: Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 hours (h) post-dose (pd) on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd
Pharmacokinetic (PK) analyses was performed after the completion of Period A and Period B of this study for all participants.
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Sample With Last Measurable Concentration (AUC[0-last]) in the Fasted and Fed States
时间窗: Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd
PK analyses was performed after the completion of Period A and Period B of this study for all participants.
Maximal Observed Plasma Concentration (Cmax) in the Fasted and Fed States
时间窗: Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd
PK analyses was performed after the completion of Period A and Period B of this study for all participants.
Minimum Observed (Trough) Plasma Concentration (Cmin) in the Fasted and Fed States
时间窗: Pre-dose on Periods A and B
Single dose Pre-dose concentration is referred as Cmin here. PK analyses was performed after the completion of Period A and Period B of this study for all participants.
Time to Reach Maximal Plasma Concentration (Tmax) in the Fasted and Fed States
时间窗: Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd
PK analyses was performed after the completion of Period A and Period B of this study for all participants.
Terminal Elimination Half-Life (t1/2) in the Fasted and Fed States
时间窗: Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd
T1/2 is the time required for the concentration of the drug to reach half of its original value. PK analyses was performed after the completion of Period A and Period B of this study for all participants.
Apparent First-order Terminal Elimination Rate Constant (Kel) in the Fasted and Fed States
时间窗: Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd
Apparent first-order terminal elimination rate constant (kel), was calculated as the negative slope of the linear regression of the terminal phase in plasma vemurafenib concentration-time profile using specific appropriate time points. PK analyses was performed after the completion of Period A and Period B of this study for all participants.
次要结局
- Overall Survival (OS)(From Baseline then Day 1 of Cycle 3 and 5 (21-day cycle) at Period C thereafter every 2 cycles until Cycle 12 followed by every 4 cycles from Cycle 13 until death (Up to Week 124))
- Percentage of Participants With Best Objective Response (BOR) as Complete Response (CR) or Partial Response (PR)(From Baseline then Day 1 of Cycle 3 and 5 (21-day cycle) at Period C thereafter every 2 cycles until Cycle 12 followed by every 4 cycles from Cycle 13 until disease progression or death (Up to Week 124))