A Biospecimen Collection Study to Evaluate the Pharmacokinetic, Pharmacodynamic, and Resistance Profile to Trametinib and Dabrafenib in BRAF-V600E Mutated Recurrent Gliomas
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 5
- 主要终点
- Concentration of trametinib in brain tumor
研究概览
简要总结
This is a surgical biospecimen collection study. The purpose of this study is to understand how much of two drugs (dabrafenib and trametinib) are able to penetrate brain tumors and turn off the RAF signaling pathway. This is important because these drugs are currently FDA approved for other tumors and may have efficacy in brain tumors with the BRAF V600E mutation.
详细描述
The primary goal of this study is to establish concentrations of dabrafenib and trametinib in enhancing brain tissue and cerebrospinal fluid from people with BRAF-V600E mutant recurrent gliomas who undergo tumor resection. The exploratory goals are to measure the amount of ERK signaling pathway activity, to identify mechanisms of resistance to these drugs, and evaluate feasibility of measuring tumor DNA in cerebrospinal fluid.
People (adults or children) with brain tumors who are already taking dabrafenib and / or trametinib and are in need of a surgical resection are potentially eligible. On the day of surgery, blood, cerebrospinal fluid, and tumor tissue will be collected for research purposes.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
入排标准
- 年龄范围
- 6 Weeks 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must have a history of primary brain tumor (including but not limited to glioblastoma (GBM), anaplastic astrocytoma (AA), anaplastic ganglioglioma (AG), and anaplastic pleomorphic xanthoastrocytoma (PXA)).
- •Subjects must have a BRAF-V600 mutation identified in previous tissue analysis (may be IHC or PCR based). Allowable mutations include V600E, V600K, V600R, and V600D.
- •Subjects must be taking dabrafenib at a dose of at least 50mg twice daily (adults only) and / or trametinib at a dose of at least 1mg daily (adults only) for at least 7 days prior to surgery as prescribed by their treating physician. Note: Pediatric patients may be taking any dose of dabrafenib and / or trametinib as prescribed by their treating physician for at least 7 days prior to surgery.
- •Subjects must be undergoing surgery for clinical purposes.
- •Written informed consent - a signed informed consent and/or assent (as age appropriate) for study participation will be obtained according to institutional guidelines.
排除标准
- •Subjects who are receiving any other investigational agents or chemotherapeutic agents.
- •Subjects for whom collection of blood, spinal fluid, or tissue samples is unsafe or clinically inadvisable.
结局指标
主要结局
Concentration of trametinib in brain tumor
时间窗: Day 1
Obtain single time-point concentration of trametinib in enhancing brain tissue (ng/mL) using liquid chromatography/mass spectrometry with one single, random sample
Concentration of dabrafenib in brain tumor
时间窗: Day 1
Obtain single time-point concentration of dabrafenib in enhancing brain tissue (ng/mL) using liquid chromatography/mass spectrometry with one single, random sample
次要结局
未报告次要终点