A Phase I, Randomized, Open-label, Multi-center, Multiple Dose Study to Investigate the Pharmacokinetics and Pharmacodynamics of RO5185426 Administered as 240 mg Tablets to Previously Treated BRAF V600E Positive Metastatic Melanoma Patients
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 52
- 主要终点
- Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 9
研究概览
简要总结
This open-label study will assess the pharmacokinetics, efficacy and safety of RO5185426 administered as 240mg tablets in previously treated patients with metastatic melanoma. Patients will be randomized to receive one of four dose-levels of RO5185426 [RG7204; PLEXXIKON; PLX4032] orally twice daily on days 1 to 15 (morning dose). Starting on day 22, treatment with RO5185426 may be resumed at a dose of 960 mg twice daily and continued until disease progression. Target sample size is <100 patients.
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
- •adult patients, >/=18 years of age
- •histologically confirmed metastatic melanoma, stage IIIc or IV (AJCC)
- •failure of at least one prior standard of care regimen
- •positive for BRAF V600E mutation (by Roche CoDx BRAF mutation assay)
- •ECOG performance status 0 or 1
- •adequate hematologic, renal and liver function
排除标准
- •active CNS lesions on CT/MRI within 28 days prior to enrollment
- •history of spinal cord compression o carcinomatous meningitis
- •anticipated or ongoing anti-cancer therapies other than those administered in this study
- •previous treatment with BRAF inhibitor (sorafenib allowed) or MEK inhibitor
- •severe cardiovascular disease within 6 months prior to 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
研究组 & 干预措施
3
干预措施: RO5185426 (Drug)
4
干预措施: RO5185426 (Drug)
1
干预措施: RO5185426 (Drug)
2
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 8 Hours (AUC[0-8h]) of Vemurafenib on Day 9
时间窗: Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 9
Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 9
时间窗: Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 9
Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24h]) of Vemurafenib on Day 15
时间窗: Pre-dose, 1, 2, 4, 5, 8, 24 hours post-dose on Day 15
Area Under the Plasma Concentration-Time Curve From Time Zero to 168 Hours (AUC[0-168h]) of Vemurafenib on Day 15
时间窗: Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15
Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 15
时间窗: Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15
Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 15
时间窗: Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15
Apparent Clearance (CL/F) of Vemurafenib on Day 15
时间窗: Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.
Terminal Elimination Half-Life (t1/2) of Vemurafenib on Day 15
时间窗: Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15
Time measured for vemurafenib plasma concentrations to decrease by one-half (t1/2) was calculated as 0.693 divided by apparent first-order terminal elimination rate constant (0.693/kel).
Accumulation Ratio of Vemurafenib on Day 15
时间窗: Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1 and 15
Accumulation ratio was calculated as, AUC(0-8) on Day 15 divided by AUC(0-8) on Day 1.
Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 1
时间窗: Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1
Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24h]) of Vemurafenib on Day 1
时间窗: Pre-dose, 1, 2, 4, 5, 8, 24 hours post-dose on Day 1
Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 1
时间窗: Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1
Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 1
时间窗: Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1
Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 9
时间窗: Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 9
Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 15
时间窗: Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 15
次要结局
- Percentage of Participants With a Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR)(Up to approximately 3 years (assessed at Cycle 1 Day 1, Cycle 3 Day 1, Cycle 5 Day 1, thereafter every 2 cycles and then every 4 cycles after Cycle 13))
- Overall Survival (OS)(Up to approximately 3 years (assessed at Cycle 1 Day 1, Cycle 3 Day 1, Cycle 5 Day 1, thereafter every 2 cycles and then every 4 cycles after Cycle 13))