A Phase Ib, Open-label, Multi-center, Dose-escalation Study of Oral BKM120 in Combination With Oral GSK1120212 in Adult Patients With Selected Advanced Solid Tumors.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 113
- 试验地点
- 3
- 主要终点
- Maximum Tolerated Dose (MTD) and/or recommended phase II dose (RP2D) and schedule of BKM120+GSK1120212
研究概览
简要总结
This is an open label, dose finding, phase Ib clinical trial to determine the maximum tolerated dose (MTD) and /or recommended phase II dose (RP2D) and schedule for the PI3K (Phosphatidylinositol 3-Kinase) inhibitor BKM120 given in combination with the MEK inhibitor GSK1120212 in patients with selected, advanced solid tumors. The focus will be on tumors with RAS/RAF mutations and on triple negative breast cancer.
Both study drugs will be administered once daily orally on a continuous schedule, a treatment cycle is defined as 28 days.
Cohorts of at least 3 and up to a maximum of 6 patients eligible for the dose-determining set will be enrolled per dose combination below the MTD. The MTD is defined as the highest drug dosage not causing in the first cycle of treatment medically unacceptable, dose-limiting toxicity (DLT) in more than 33% of the treated patients.. At least 12 patients will be required at MTD and 6 patients at RP2D level to allow the evaluation of the combination's safety and pharmacokinetics or pharmacodynamics.
Upon declaration of MTD and/or RP2D, patients will be enrolled to an expansion part of the study, to further assess safety, as well as to learn more about the efficacy of the study drug combination.
- Expansion Arm 1 will consist of approximately 15 patients with RAS or BRAF mutant advanced NSCLC
- Expansion Arm 2 will consist of approximately 15 patients with RAS or BRAF-mutant ovarian cancer
- Expansion Arm 3 will consist of approximately 15 patients with RAS or BRAF-mutant pancreatic cancer
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •histologically/ cytologically confirmed, advanced non resectable solid tumors
- •Measurable or non-measurable, but evaluable disease as determined by RECIST 1.0
排除标准
- •Patients with primary Central Nervous System (CNS) tumor or CNS tumor involvement.
- •Clinically manifested diabetes mellitus - Unacceptable ocular/retinal conditions
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
BKM120 + GSK1120212 ovarian cancer patients
Advanced RAS or BRAF mutant ovarian cancer patients
干预措施: BKM120 (Drug)
BKM120 + GSK1120212 ovarian cancer patients
Advanced RAS or BRAF mutant ovarian cancer patients
干预措施: GSK1120212 (Drug)
BKM120 + GSK1120212 NSCLC patients
Advanced RAS or BRAF mutant NSCLC patients
干预措施: BKM120 (Drug)
BKM120 + GSK1120212 NSCLC patients
Advanced RAS or BRAF mutant NSCLC patients
干预措施: GSK1120212 (Drug)
BKM120 + GSK1120212 DE
Dose Escalation
干预措施: BKM120 (Drug)
BKM120 + GSK1120212 DE
Dose Escalation
干预措施: GSK1120212 (Drug)
BKM120 + GSK1120212 pancreatic cancer patients
Advanced RAS or BRAF mutant pancreatic cancer patients
干预措施: BKM120 (Drug)
BKM120 + GSK1120212 pancreatic cancer patients
Advanced RAS or BRAF mutant pancreatic cancer patients
干预措施: GSK1120212 (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) and/or recommended phase II dose (RP2D) and schedule of BKM120+GSK1120212
时间窗: in average 1 year
次要结局
- Measure the number of Adverse Event and laboratory values that fall outside of pre-determined ranges as a measure of Safety and tolerability of the oral combination of BKM120 and GSK1120212(in average 1 year)
- Preliminary anti-tumor activity of the combination(Assessed every 8 weeks of treatment)
- Molecular status (genetic alterations, protein expression and/or activation) of markers related to PI3K and ERK signaling in tumor tissue and blood and investigate their potential relationship to clinical responses(Assessed at baseline (pre-treatment))
- Determine the single and multiple dose pharmacokinetics of BKM120 and GSK1120212 in measurement of the plasma concentration profiles of BKM120 and GSK1120212(Assessed during the first Cycle (28 days) of treatment)
- Treatment-induced PI3K and MEK/ERK(Mitogen-activated protein kinase /extracellular-signal-regulated kinases) pathway signaling inhibition and evidence of biological activity in tumor and skin(Assessed every 2 weeks during the first cycle, then every 4 weeks)