NCT01352273已完成1 期
A Phase Ib Open-label Dose Escalation Study of MEK162 and RAF265 in Adult Patients With Advanced Solid Tumors Harboring RAS or BRAFV600E Mutations
Array Biopharma, now a wholly owned subsidiary of Pfizer4 个研究点 分布在 2 个国家目标入组 69 人开始时间: 2011年6月最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 69
- 试验地点
- 4
- 主要终点
- Incidence of Dose Limiting Toxicities
研究概览
简要总结
This is a multi- center, open-label, dose finding, Phase Ib study to be conducted in two stages: a dose escalation part to determine the maximum tolerated dose (MTD) safety and tolerability of concurrent administration of MEK162 and RAF265, followed by an expansion part to further assess the safety and preliminary anti-tumor efficacy of this oral combination within two separate patient populations: i) patients with advanced solid tumors harboring BRAFV600E mutations or ii) patients with advanced solid tumors harboring RAS mutations.
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
- •Patients with histologically or cytologically confirmed and non-resectable advanced solid tumors for which no further effective standard therapy exists.
- •The patients' tumors must contain documented activating somatic BRAFV600E* , NRAS or KRAS mutations (except for pancreatic cancer)
- •All patients enrolled MUST provide fresh or archival tumor samples at baseline to enable central confirmation of BRAF or KRAS/NRAS mutations
- •Measurable, or non-measurable but evaluable disease as determined by RECIST
- •Adequate bone marrow function
- •Adequate hepatic and renal function
- •Adequate cardiovascular function
- •Negative serum β HCG test (female patients of childbearing potential only) within 72 hrs prior to first dose
排除标准
- •Patients with a history of primary central nervous system tumors or brain metastases or who have signs/symptoms attributable to brain metastases and have not been assessed with radiologic imaging to rule out the presence of brain metastases
- •Current evidence of retinal disease; or ophthalmopathy as assessed by ophthalmologic examination at baseline that would be considered a risk factor for CSR/RVO (e.g., optic disc cupping, visual field defects, IOP > 21 mm Hg)
- •Impaired cardio-/vascular function or clinically significant cardiovascular diseases, including any of the following:
- •History/evidence of acute coronary syndromes (including MI, unstable angina, CABG, coronary angioplasty, or stenting) ≤ 6 months prior to starting study drugs
- •Thromboembolic event (DVT, CVA, PE) ≤ 6 months prior to starting study
- •Symptomatic CHF, history or current evidence of clinically significant cardiac arrhythmia and/or conduction abnormality
- •Uncontrolled arterial hypertension, defined as BP > 140/100 mmHg (average of 3 consecutive readings)
- •History of melena, hematemesis or hemoptysis within the last 3 months
- •Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL)
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
MEK162 + RAF265
Experimental
干预措施: MEK162 + RAF265 (Drug)
结局指标
主要结局
Incidence of Dose Limiting Toxicities
时间窗: during the first 28 days of treatment with RAF265 and MEK162
次要结局
- Number of participants with adverse events and serious adverse events(18 months)
- Tumor skin and blood samples will be collected before and during treatment with RAF265 and MEK162 to assess the combination's effects on the RAF/MEK/MAPK pathway with the clinical outcomes(18 months)
- Time versus plasma concentration profiles of RAF265 and MEK162(10 months)
- assess preliminary anti-tumor activity of the combination(every 8 weeks of treatment)
研究者
研究点 (4)
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