An Open-Label, Multiple Ascending Dose (MAD) Study of the Selective BRAF Inhibitor RO5212054 (PLX3603) to Evaluate Safety, Tolerability and Pharmacokinetics in Patients With BRAF V600-Mutated Advanced Solid Tumours
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 45
- 试验地点
- 5
- 主要终点
- Percentage of Participants With Dose Limiting Toxicity
研究概览
简要总结
This open-label, multi-center study will evaluate the safety, tolerability, and pharmacokinetics of RO5212054 [PLX3603] in participants with BRAF V600-mutated advanced solid tumors. Cohorts of participants will receive escalating oral doses of RO5212054. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.
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
- •Advanced solid tumor
- •Dose-escalation phase: Histologically confirmed, newly diagnosed or relapsed/ refractory unresectable American Joint Committee on Cancer (AJCC) Stage IIIC or IV disease
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •Adequate liver, renal and bone marrow function
排除标准
- •Participants for whom standard therapy exists and is considered appropriate by the investigator
- •Prior treatment with an inhibitor of BRAF (sorafenib allowed)
- •Active Central nervous system (CNS) lesions, or history of or known carcinomatous meningitis
- •Treatment with any chemotherapy, radiotherapy, immunotherapy or investigational agent within 28 days prior to first dose of study drug
- •Anticipated or ongoing anti-cancer therapies other than those administered in this study
- •Serious cardiovascular illness within the 6 months prior to study drug administration
研究组 & 干预措施
RO5212054: Continuous Dosing Cohort
Participants will receive RO5212054 in escalating dose levels.
干预措施: RO5212054 (Drug)
RO5212054: New Formulation (F05) Bridging Cohort
Participants will receive RO5212054 as a single dose of new formulation (F05-150 mg film-coated tablet with different ratios of ingredients than F03 to increase bioavailability) and a single dose of current clinical Formulation (F03-150 mg film-coated tablet) in a cross-over manner. Participants will be alternately assigned to receive either F05 or F03 as their first dose, followed by the opposite Formulation as their second dose. Dose of RO5212054 will be decided based on the results of continuous dosing cohort.
干预措施: RO5212054 (Drug)
结局指标
主要结局
Percentage of Participants With Dose Limiting Toxicity
时间窗: Baseline up to 21 days
Maximal Tolerated Dose of RO5212054
时间窗: Baseline up to 21 days
Maximum Plasma Concentration of RO5212054
时间窗: Baseline up to cycle 10 (cycle length: 21 days) (detailed timeframe is given in description)
Detailed timeframe: Pre-dose (0 hour \[hr\]): Day 1 of Cycles 1-10; Days 4, 8, 15 of Cycle 1. Post-dose: 1, 2, 4, 8, 12, 24 hr on Day 1 Cycle 1; Between 2-4 hr (1 sample) on Day 8 Cycle 1 and Day 1 Cycles 2-9; 1, 2, 4, 8, Between 10-12 hr (1 sample), 24 hr on Day 15 Cycle 1 (cycle length: 21 days)
Time to Reach Maximum Plasma Concentration of RO5212054
时间窗: Baseline up to cycle 10 (cycle length: 21 days) (detailed timeframe is given in description)
Detailed timeframe: Pre-dose (0 hr): Day 1 of Cycles 1-10; Days 4, 8, 15 of Cycle 1. Post-dose: 1, 2, 4, 8, 12, 24 hr on Day 1 Cycle 1; Between 2-4 hr (1 sample) on Day 8 Cycle 1 and Day 1 Cycles 2-9; 1, 2, 4, 8, Between 10-12 hr (1 sample), 24 hr on Day 15 Cycle 1 (cycle length: 21 days)
Area Under The Plasma Concentration-Time Curve of RO5212054
时间窗: Baseline up to cycle 10 (cycle length: 21 days) (detailed timeframe is given in description)
Detailed timeframe: Pre-dose (0 hr): Day 1 of Cycles 1-10; Days 4, 8, 15 of Cycle 1. Post-dose: 1, 2, 4, 8, 12, 24 hr on Day 1 Cycle 1; Between 2-4 hr (1 sample) on Day 8 Cycle 1 and Day 1 Cycles 2-9; 1, 2, 4, 8, Between 10-12 hr (1 sample), 24 hr on Day 15 Cycle 1 (cycle length: 21 days)
次要结局
- Percentage of Participants With Adverse Events(Baseline up to approximately 7 years)