A Phase 1/2 Trial of BKM120 Combined With Vemurafenib (PLX4032) in BRAFV600E/K Mutant Advanced Melanoma (Novartis Study Number CBKM120ZUS21T)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Phase 1 - Safety & Recommended Phase 2 Dose (RP2D)
研究概览
简要总结
This is a phase 1/2 clinical trial with the goal of determining whether the addition of the investigational agent BKM120 to vemurafenib will lead to improved 6-month progression-free survival in patients with BRAFV600E/K mutant melanoma.
详细描述
The phase 1 portion of this trial is a dose escalation study; the phase 2 portion is a single-stage, single arm prospective clinical trial. All patients will receive continuous doses of vemurafenib twice a day and BKM120 once a day.
In the phase 1 portion of the study, there will be a 7 day lead-in period to allow for single dose pharmacokinetic analysis of BKM120 alone. Cycle 1 (28 days) is the dose-limiting toxicity (DLT) period. During phase 1, vemurafenib and BKM120 doses will be escalated using a standard 3+3 dose escalation scheme with the goal of identifying the recommended phase 2 dose.
In the phase 2 portion of the study, patients will receive continuous doses of vemurafenib and BKM120 starting on day 1 of the first cycle. In the phase 2 portion of the study, patients will receive vemurafenib and BKM120 at the recommended phase 2 dose.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
No Previous Treatment
150 mg oral dabrafenib twice a day until disease progression, death, or unacceptable adverse events.
干预措施: BKM120 Combined with Vemurafenib (PLX4032) (Drug)
结局指标
主要结局
Phase 1 - Safety & Recommended Phase 2 Dose (RP2D)
时间窗: 28 days
RP2D determined by maximum tolerated dose (MTD), post-dose-limiting toxicity (DLT) period toxicity, and pharmacokinetic data
Phase 2 - Progression-free Survival Rate
时间窗: 6 months
6 month progression-free survival rate (PFS6) determined by tumor assessments, clinical tests and laboratory tests
次要结局
- Secondary Outcome 1 Phase 2 - Objective Response Rate(Day 28 (+/- 3) of even-numbered treatment cycles until progression)
- Secondary Outcome 4 Phase 2 - Phosphatidylinositol 3-kinase (PI3K)-Pathway Signaling Reduction Levels(No time limit)
- Secondary Outcome 6 Phase 2 - MAPK Pathway Gene Expression Levels(No time limit)
- Secondary Outcome 2 Phase 2 - Safety and Tolerability(During study treatment, up to 2 years)
- Secondary Outcome 3 Phase 2 - Phosphatase and TENsin (PTEN) Expression(No time limit)
- Secondary Outcome 5 Phase 2 - PI3K Pathway Gene Expression Levels(No time limit)
研究者
Alain Algazi
Assistant Clinical Professor - Melanoma Oncology
University of California, San Francisco