A Phase 1/2 Trial of Trametinib and Erlotinib in Patients With EGFR-Mutant Lung Adenocarcinomas and Acquired Resistance to Erlotinib
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 7
- 主要终点
- Participants Response Rate
研究概览
简要总结
The purpose of this study is to determine the safety, tolerability and overall response rate of trametinib when given in combination with erlotinib in patients with Stage IV or recurrent lung adenocarcinoma that cannot be treated with curative intent.
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
- •Pathologic evidence of advanced stage IV or recurrent lung adenocarcinoma reviewed at MSKCC
- •Somatic activating mutation in EGFR Radiographic progression during treatment with erlotinib.
- •Any number of prior chemotherapy regimens is permitted.
- •Measurable (RECIST 1.1) indicator lesion not previously irradiated
- •KPS >/= 70%
- •Age >18 years old
- •Must have undergone biopsy after development of acquired resistance to erlotinib with available archived tissue (equivalent of > 10 unstained slides)
- •Left ventricular Ejection Fraction >/= the lower limit of normal by ECHO or MUGA
- •Adequate organ function:
- •AST, ALT </= 2.5 x ULN
- •Total bilirubin </= 1.5 x ULN
- •Albumin>/=2.6g/dL - Creatinine < 1.5 x ULN OR calculated creatinine clearance >/=50mL/min
- •Absolute neutrophil count (ANC) >/= 1,200 cells/mm3
- •Hemoglobin>/=9.0 g/dL
- •Platelets >/=100,000/mm3
排除标准
- •Patients with symptomatic brain metastasis requiring escalating doses of steroids
- •Patients with grade 2 or greater diarrhea prior to study initiation despite maximal medical management due to medications or a medical condition such as Crohn's disease or malabsorption
- •Pregnant or lactating women
- •Any type of systemic therapy (chemotherapy or experimental drugs) within 2 weeks of starting treatment on protocol except for a EGFR TKI
- •Patients who have received prior treatment with a MEK inhibitor
- •Any major surgery or extensive radiotherapy within 21 days of starting treatment on protocol.
- •A history of clinically significant interstitial lung disease or pneumonitis
- •Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months from Day 1 of study administration, New York Heart Association Class III or IV congestive heart failure, or symptomatic uncontrolled Arrythmias, prolonged corrected QT interval >480msec, treatment refractory hypertension, presence of a cardiac defibrillator
- •History of central serous retinopathy or retinal vein occlusion
研究组 & 干预措施
Trametinib 1.5mg + Erlotinib 75mg
Phase 1: Accrue 6 patients on Trametinib 1.5mg + Erlotinib 75mg by mouth once daily Phase 2: Accrue 24 patients (including 6 patients treated during Phase 1) on Trametinib 1.5mg + Erlotinib 75mg by mouth once daily or Trametinib 1.0mg + Erlotinib 100mg by mouth once daily.
干预措施: Trametinib (Drug)
Trametinib 1.5mg + Erlotinib 75mg
Phase 1: Accrue 6 patients on Trametinib 1.5mg + Erlotinib 75mg by mouth once daily Phase 2: Accrue 24 patients (including 6 patients treated during Phase 1) on Trametinib 1.5mg + Erlotinib 75mg by mouth once daily or Trametinib 1.0mg + Erlotinib 100mg by mouth once daily.
干预措施: Erlotinib (Drug)
结局指标
主要结局
Participants Response Rate
时间窗: 2 years
Response and progression of disease will be evaluated in this study using interval imaging every 8 weeks with CT scan of the chest and imaging of any other target lesion with response evaluated by RECIST 1.1.
Number of Participants Evaluated for Toxicities
时间窗: 2 years
Safety and tolerability will be evaluated by systematic and regular toxicity evaluations. Toxicity will be graded according to NCI CTCAE version 4.0.
次要结局
未报告次要终点