Phase II Trial of Hyd-sulfate AZD6244 [NSC 748727] in Patients With BRAF or NRAS Mutated Melanomas
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 167
- 试验地点
- 1
- 主要终点
- Anti-tumor Response Defined as Either a CR, PR, or SD as Defined by RECIST
研究概览
简要总结
This phase II trial is studying how well MEK inhibitor AZD6244 works in treating patients with stage III or stage IV melanoma. MEK inhibitor AZD6244 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
详细描述
PRIMARY OBJECTIVES:
I. Determine the response in patients with V600E or V600K BRAF-mutated or NRAS-mutated stage III or stage IV melanoma with low or high phospho-pAKT expression treated with MEK inhibitor AZD6244.
SECONDARY OBJECTIVES:
I. Identify other genetic predictors of sensitivity to MEK inhibition.
OUTLINE: Patients are stratified according to pAKT expression (low vs high).
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
- •Histologically or cytologically confirmed melanoma
- •Stage IV or stage III disease not potentially curable with surgery
- •Documented tumor progression
- •Must have a V600E or V600K BRAF-mutated tumor, or a NRAS mutation at condons 12, 13, or 61
- •Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan
- •Must have tumor tissue (block or unstained slides) available for IHC studies
- •No primary uveal or mucosal melanoma
- •No active or untreated brain metastases
- •Treated brain metastases allowed provided they have been stable for ≥ 3 months
- •ECOG performance status 0-1
- •Life expectancy > 3 months
- •WBC ≥ 3,000/mcL
- •Absolute neutrophil count ≥ 1,500/mcL
- •Platelet count ≥ 100,000/mcL
- •Hemoglobin ≥ 9.0 g/dL (no requirement for transfusions within the past 2 weeks)
- •Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
- •AST/ALT ≤ 2.5 times ULN
- •Creatinine ≤ 1.5 mg/dL
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception during and for 16 weeks after completion of study treatment
- •No refractory nausea and vomiting, chronic gastrointestinal disease (e.g., inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption
- •No concurrent uncontrolled illness, including, but not limited to, any of the following:
- •Ongoing or active infection or bleeding
- •Symptomatic congestive heart failure
- •Unstable angina pectoris
- •Cardiac arrhythmia
- •Psychiatric illness/social situation that would limit compliance with study requirements
- •No history of allergic reactions attributed to compounds of similar chemical or biologic composition to MEK inhibitor AZD6244
- •Any number of prior therapies allowed
- •At least 4 weeks since prior radiotherapy or chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered
- •At least 4 months since prior anti-CTLA4 monoclonal antibody therapy
- •At least 4 weeks since other prior systemic therapy
- •No other concurrent investigational agents
- •No concurrent antiretroviral therapy for HIV-positive patients
- •No concurrent vitamin E supplementation or multivitamin supplements that provide a total daily dose in excess of 100% of the recommended daily dose of vitamin E
- •No concurrent anticancer chemotherapy or other systemic drugs
- •Concurrent palliative radiotherapy allowed
排除标准
- 未提供
研究组 & 干预措施
Arm I
Patients receive oral MEK inhibitor AZD6244 twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Arm I
Patients receive oral MEK inhibitor AZD6244 twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Selumetinib (Drug)
结局指标
主要结局
Anti-tumor Response Defined as Either a CR, PR, or SD as Defined by RECIST
时间窗: Up to 4 weeks
Anti-tumor response defined as either a Complete Response, Partial Response, or Stable Disease as defined by RECIST
次要结局
未报告次要终点