Phase 1 Study of Combination Dacomitinib and Osimertinib for Patients With Metastatic EGFR Mutant Lung Cancers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 7
- 主要终点
- Best overall response rate
研究概览
简要总结
The purpose of this study is to test the safety of dacomitinib and osimertinib, at increasing doses, to find out what effects, if any, this combination of drugs has on people with metastatic EGFR mutant lung cancer that has not been treated with an EGFR TKI.
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
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent
- •Advanced biopsy-proven metastatic non-small cell lung cancer
- •Somatic activating mutation in EGFR in a tumor biopsy
- •No prior EGFR inhibitor treatment (gefitinib, afatinib, erlotinib, dacomitinib, osimertinib) however, prior treatment with other chemotherapies are allowed
- •Archival tissue available from a pre-treatment tumor biopsy or willing to undergo a tumor biopsy prior to study initiation.
- •Measurable (RECIST 1.1) indicator lesion not previously irradiated
- •Karnofsky performance status (KPS) ≥ 70%
- •Age >18 years old
- •Ability to swallow oral medication
- •Agree to use effective methods of contraception from the time of screening until 3 months after treatment discontinuation (for males and females of child-bearing potential)
- •Adequate organ function
- •AST, ALT ≤ 3 x ULN
- •Total bilirubin ≤1.5x ULN
- •Creatinine ≤ 1.5x ULN OR calculated creatinine clearance ≥ 60ml/min
- •Absolute neutrophil count (ANC) ≥ 1000 cells/mm^3
- •Hemoglobin≥9.0 g/dL
- •Platelets ≥100,000/mm^3
排除标准
- •Pregnant or lactating women
- •Any radiotherapy within 1 week of starting treatment on protocol.
- •Any major surgery within 1 weeks of starting treatment on protocol.
- •Any evidence of active clinically significant interstitial lung disease
- •A mean QTc >470ms (Fridericia"s correction), clinically important arrhythmia, conduction or morphology of resting ECG (eg complete LBBB, 1st -3rd degree heart block, any factors that increase the risk of QTc prolongation or risk of arrhythmia)
- •Cardiovascular disease or cerebrovascular disease, CVA or MI < 6 months prior to study enrollment, unstable angina, NYHA >Grade II CHF, or serious cardiac arrhythmia uncontrolled by medication or with the potential to interfere with protocol treatment
- •History of pneumonitis or interstitial lung disease (ILD), drug induced ILD, radiation pneumonitits that required steroid treatment, and any evidence of clinically active ILD
- •Serious chronic GI conditions associated with diarrhea
- •Symptomatic, unstable brain metastases requiring escalating doses of steroids
- •Continue to have unresolved > CTCAE grade 1 toxicity from any previous treatment
研究组 & 干预措施
Dacomitinib and Osimertinib
Patients will begin on combination dacomitinib and osimertinib at the prescribed doses.
A cycle will be 28 days in duration. The study will use a standard 3+3 dose escalation design. Per MD discretion, telemedicine visits may be utilized for cycles where imaging is not collected, and physical exam, vital sign and labs collection will only be required concurrent with imaging visits.
干预措施: Dacomitinib (Drug)
Dacomitinib and Osimertinib
Patients will begin on combination dacomitinib and osimertinib at the prescribed doses.
A cycle will be 28 days in duration. The study will use a standard 3+3 dose escalation design. Per MD discretion, telemedicine visits may be utilized for cycles where imaging is not collected, and physical exam, vital sign and labs collection will only be required concurrent with imaging visits.
干预措施: Osimertinib (Drug)
结局指标
主要结局
Best overall response rate
时间窗: 1 year
Tumor response will be assessed using RECIST 1.1.The NCI Common Terminology Criteria for Adverse Events Version 5 (NCI-CTCAE) will be used to grade toxicities during the trial. Dose-limiting toxicities (DLT"s) are defined as any of the following events occurring during the first cycle of treatment
maximum tolerated dose
时间窗: 1 year
The MTD will be defined as the highest dose at which not more than 1/6 of the patients experience dose limiting toxicity (DLT). DLT is defined as any of the toxicity events described below that occurs within cycle 1 of treatment with the combination of dacomitinib and osimertinib.
次要结局
未报告次要终点