Phase 1 Trial of Osimertinib With Stereotactic Radiosurgery (SRS) in Patients With Brain Metastases From EGFR Positive Non-Small-Cell Lung Cancer (NSCLC)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 6
- 试验地点
- 2
- 主要终点
- Maximum Tolerated Dose (MTD) of Osimertinib with (SRS)
研究概览
简要总结
Investigating potential of controlling brain metastases in patients with EGFR positive NSCLC.
详细描述
In patients with EGFR positive NSCLC with 1-10 brain metastases, we are investigating whether we can control the macro brain metastases with Stereotactic Radiosurgery (SRS) and control the micro metastases with targeted agent Osimertinib and avoid whole brain radiation that could potentially lead to significant cognitive decline.
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
- •Confirmed pathology of EGFR mutation positive NSCLC with new brain metastases.
- •Ability to care for self and ability to walk 50% of waking hours (ECOG Performance Status of 0-2)
- •1-10 brain metastases with intra-cranial brain metastasis must measure 3cm or less in the greatest dimension.
- •Hemoglobin ≥9 g/dL, White Blood Count Absolute ≥3.0 x 10^9/L, Granulocyte count ≥1.5 x 10^9/L, and platelet count ≥100 x 10^9/L
- •Serum Bilirubin ≤ 1.5 x upper limit of normal (ULN)
- •AST and/or ALT ≤ 2 ULN (≤ 5 x ULN when clearly attributable to liver metastases)
- •Serum creatinine ≤ 1.5 ULN or calculated creatinine clearance > 60ml/min
- •For women of childbearing potential-Negative pregnancy test within one week prior to start of therapy.
- •For all sexually active male and female patients of reproductive potential, employ two methods of highly effective and acceptable forms of contraception throughout the study and for 120 days following the final dose of osimertinib.
排除标准
- •Patients with leptomeningeal metastases documented by MRI or cerebrospinal fluid (CSF).
- •Significant intratumoral or peritumoral hemorrhage
- •Brain metastases within 5 mm of the optic chiasm or optic nerve
- •Brainstem metastases
- •Gastrointestinal disorders with diarrhea as a major symptom
- •Clinically significant or uncontrolled cardiac disease (NYHA functional classification of 3 or 4)
- •Pre-existing interstitial lung disease or pneumonitis
- •Unable to undergo brain MRI
- •HIV or Hepatitis B or C
- •Prior treatments must be resolved to an asymptomatic state at time of enrollment
- •Medical conditions that could cause safety risks
- •Currently receiving investigational cancer therapy.
- •Mean QT interval corrected heart rate (QTc)≥470ms calculated from 3 EKGs
- •Left Ventricular Ejection Fraction (LVEF) ≤ 50%
- •Use of strong CYP3A inhibitors
- •Use of strong CYP3A4 inducers
- •Use of potent CYP2C8 inhibitors
- •Hypersensitivity to osimertinib or any of its ingredients
- •corneal ulceration
- •pregnant or breast-feeding
研究组 & 干预措施
Maximum Tolerated Dose of Osimertinib with standard of care
For patients with 1-10 brain metastases, begin daily Osimeritinib 0-7 days prior to stereotactic radiosurgery (SRS), provide daily Osimeritinib concurrently with radiotherapy, followed by maintenance Osimeritinib until disease progression, withdrawal, or unacceptable toxicity. Dose Level 1: 80mg daily. Dose Level -1: 40mg daily
干预措施: Osimertinib (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Osimertinib with (SRS)
时间窗: 4 weeks
To determine the safety, tolerability and maximum tolerated dose of Osimertinib, when administered in combination with SRS in patients with EGFR positive NSCLC with brain metastases.
次要结局
- Length of overall survival(2 years)
- Number of patients with progression free survival(6 months)
- Difference in outcome vs. standard of care(2 years)
- Intra-cranial and Extra-cranial Overall Response Rate (ORR)(6 months)