Phase 1 Study of Combination Osimertinib, Platinum, Etoposide for Patients With Metastatic EGFR Mutant Lung Cancers With Concurrent RB1 and TP53 Alterations
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 11
- 试验地点
- 12
- 主要终点
- The MTD (maximum tolerated dose)
研究概览
简要总结
The purpose of this study is to test the safety of combining Osimertinib with either Cisplatin or Carboplatin (at different dose levels) and Etoposide, to find out what effects, if any, this combination of drugs has on people with EGFR mutant lung cancer.
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
- •Written informed consent
- •Advanced biopsy-proven metastatic non-small cell lung cancer
- •Either have not started an EGFR TKI or may have started osimertinib within the last 9 weeks
- •Somatic activating mutation in EGFR in pre-treatment tumor biopsy or cfDNA
- •Evidence of a concurrent P53 alteration by IHC or NGS on pre-treatment tumor biopsy or cfDNA
- •Evidence of a concurrent RB1 alteration by IHC or NGS on pre-treatment tumor biopsy or cfDNA
- •Must have a site of disease amenable to repeat biopsy and be willing to undergo a biopsy during treatment
- •Measurable (RECIST 1.1) indicator lesion not previously irradiated
- •Karnofsky performance status (KPS) ≥ 70%
- •Age >18 years old
- •Ability to swallow oral medication
- •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≥8.0 g/dL
- •Platelets ≥100,000/mm^3
排除标准
- •Pregnant or lactating women
- •Started an EGFR TKI other than osimertinib or started osimertinib more than 9 weeks ago
- •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
- •Continue to have unresolved > grade 1 toxicity from any previous treatment
- •Have pure small cell histology
- •Corrected QT interval using Fridericia's formula (QTcF)>475msec or any clinically significant (as deemed by the investigator) abnormalities in rhythm or conduction or morphology of the resting EKG.
- •Patients are to be excluded from cisplatin treatment arm if they meet any of the following criteria:
- •Creatinine clearance < 60 ml/min
- •Hearing impairment requiring assistive device
- •Neuropathy
- •The treating provider does not feel as though the patient should receive cisplatin
研究组 & 干预措施
Osimertinib, Platinum (cisplatin or carboplatin) and Etoposide
Initially, 6 patients will be enrolled and will begin treatment with osimertinib 80mg orally daily (3 who will be receiving cisplatin and 3 who will be receiving carboplatin). Cisplatin or carboplatin treatment will be decided by the treating physician prior to study registration. After 9 weeks (+/- 1 week)( 3 cycles) on osimertinib alone, carboplatin or cisplatin and etoposide will be added. Carboplatin is doses at an AUC of 5 or cisplatin at 60mg/m2 will be given on C4D1. Etoposide is dosed at 100mg/m2 given on Days 1-3 of C4. Only patients on osimertinib 80mg orally daily at the start of cycle 4 will be included in the 3+3 dose de-escalation portion of the study. Chemotherapy and osimertinib will be administered concurrently during cycles 4-7, and from cycle 8 onward, osimertinib monotherapy will be continued. Patients will present every 2 cycles post-chemo (Cycles 8, 10, 12, etc.)
干预措施: Osimertinib (Drug)
Osimertinib, Platinum (cisplatin or carboplatin) and Etoposide
Initially, 6 patients will be enrolled and will begin treatment with osimertinib 80mg orally daily (3 who will be receiving cisplatin and 3 who will be receiving carboplatin). Cisplatin or carboplatin treatment will be decided by the treating physician prior to study registration. After 9 weeks (+/- 1 week)( 3 cycles) on osimertinib alone, carboplatin or cisplatin and etoposide will be added. Carboplatin is doses at an AUC of 5 or cisplatin at 60mg/m2 will be given on C4D1. Etoposide is dosed at 100mg/m2 given on Days 1-3 of C4. Only patients on osimertinib 80mg orally daily at the start of cycle 4 will be included in the 3+3 dose de-escalation portion of the study. Chemotherapy and osimertinib will be administered concurrently during cycles 4-7, and from cycle 8 onward, osimertinib monotherapy will be continued. Patients will present every 2 cycles post-chemo (Cycles 8, 10, 12, etc.)
干预措施: Platinum (Drug)
Osimertinib, Platinum (cisplatin or carboplatin) and Etoposide
Initially, 6 patients will be enrolled and will begin treatment with osimertinib 80mg orally daily (3 who will be receiving cisplatin and 3 who will be receiving carboplatin). Cisplatin or carboplatin treatment will be decided by the treating physician prior to study registration. After 9 weeks (+/- 1 week)( 3 cycles) on osimertinib alone, carboplatin or cisplatin and etoposide will be added. Carboplatin is doses at an AUC of 5 or cisplatin at 60mg/m2 will be given on C4D1. Etoposide is dosed at 100mg/m2 given on Days 1-3 of C4. Only patients on osimertinib 80mg orally daily at the start of cycle 4 will be included in the 3+3 dose de-escalation portion of the study. Chemotherapy and osimertinib will be administered concurrently during cycles 4-7, and from cycle 8 onward, osimertinib monotherapy will be continued. Patients will present every 2 cycles post-chemo (Cycles 8, 10, 12, etc.)
干预措施: Etoposide (Drug)
结局指标
主要结局
The MTD (maximum tolerated dose)
时间窗: 2 years
Determine the safety and toxicity profile of combination osimertinib, platinum (cisplatin or carboplatin), etoposide for patients with metastatic EGFR mutant lung cancers with concurrent RB1 and TP53 alterations.
次要结局
未报告次要终点