A Dose-Finding Study Of Afatinib In Combination With Cisplatin Or Carboplatin + Pemetrexed In Patients With EGFR-Mutant Lung Cancers Undergoing Definitive Chemoradiation
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- maximum tolerated dose
研究概览
简要总结
The purpose of this Phase I study is to test the safety of combining afatinib with standard chemotherapy and radiation. The drug afatinib will be given before the chemotherapy and radiation therapy to shrink the tumor and evaluate how afatinib affects the patient. This study will then test the safety of afatinib at different dose levels when combined with the chemotherapy drugs cisplatin or carboplatin, and pemetrexed. These treatments will be given during radiation treatment and the drug afatinib will be continued after chemotherapy and radiation.
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
- •Unresectable or inoperable, stage III or locoregional recurrence without evidence of distant, metastatic disease
- •Pathologic confirmation of NSCLC at MSKCC
- •Documentation of a sensitizing EGFR mutation
- •Age ≥ 18 years
- •No contraindication to definitive thoracic radiation therapy with concurrent chemotherapy
- •Adequate organ function as defined by:
- •Calculated creatinine clearance≥ 45 mL/min (by Cockcroft-Gault)
- •Total bilirubin less than 1.5 x ULN (unless known Gilbert's disease) and AST/ALT less than 3 x ULN
- •Absolute neutrophil count greater than 1500/mm3
- •Platelet count greater than 100,000/mm3
- •Women of childbearing age must have a negative blood pregnancy test
- •Men and women of childbearing potential must be willing to use effective contraception while on treatment and for at least 3 months there after
排除标准
- •Prior chemotherapy or radiation therapy for this lung cancer (history of prior lung cancer that has been treated and deeded inactive by the clinician is acceptable)
- •Ineligible for cisplatin or carboplatin per medical oncologist
- •Ineligible for pemetrexed per medical oncologist
- •Greater than minimal, exudative, or malignant pleural effusion
- •Calculated creatinine clearance by Cockcroft & Gault method ≤45 ml/min
- •Unstable congestive heart failure
- •Ejection fraction <50% as assessed by MUGA or echocardiogram
- •Interstitial lung disease
- •Patient requiring on-going treatment with a potent inhibitor (cyclosporin, erythromycin, ketoconazole, itraconazole, quinidine, phenobarbital with quinidine, ritonavir, valspodar, verapamil) or inducer of P-gp (St. John's wort or rifampin)
- •Women who are breastfeeding
研究组 & 干预措施
Afatinib w Cisplatin Pemetrexed Chemoradiation
induction afatinib 40mg daily x 28days Cisplatin or Carboplatin (can be used if patient is not eligible for cisplatin) + Pemetrexed + 50Gy to pretreatment field boost to 60Gy to residual tumor + afatinib dose escalation*
*afatinib dose levels: 20mg daily, 30mg daily & 40mg daily (3+3 design) Then adjuvant afatinib x 2 years
干预措施: Afatinib (Drug)
Afatinib w Cisplatin Pemetrexed Chemoradiation
induction afatinib 40mg daily x 28days Cisplatin or Carboplatin (can be used if patient is not eligible for cisplatin) + Pemetrexed + 50Gy to pretreatment field boost to 60Gy to residual tumor + afatinib dose escalation*
*afatinib dose levels: 20mg daily, 30mg daily & 40mg daily (3+3 design) Then adjuvant afatinib x 2 years
干预措施: Cisplatin (Drug)
Afatinib w Cisplatin Pemetrexed Chemoradiation
induction afatinib 40mg daily x 28days Cisplatin or Carboplatin (can be used if patient is not eligible for cisplatin) + Pemetrexed + 50Gy to pretreatment field boost to 60Gy to residual tumor + afatinib dose escalation*
*afatinib dose levels: 20mg daily, 30mg daily & 40mg daily (3+3 design) Then adjuvant afatinib x 2 years
干预措施: Carboplatin (Drug)
Afatinib w Cisplatin Pemetrexed Chemoradiation
induction afatinib 40mg daily x 28days Cisplatin or Carboplatin (can be used if patient is not eligible for cisplatin) + Pemetrexed + 50Gy to pretreatment field boost to 60Gy to residual tumor + afatinib dose escalation*
*afatinib dose levels: 20mg daily, 30mg daily & 40mg daily (3+3 design) Then adjuvant afatinib x 2 years
干预措施: Pemetrexed (Drug)
Afatinib w Cisplatin Pemetrexed Chemoradiation
induction afatinib 40mg daily x 28days Cisplatin or Carboplatin (can be used if patient is not eligible for cisplatin) + Pemetrexed + 50Gy to pretreatment field boost to 60Gy to residual tumor + afatinib dose escalation*
*afatinib dose levels: 20mg daily, 30mg daily & 40mg daily (3+3 design) Then adjuvant afatinib x 2 years
干预措施: Radiation therapy (Radiation)
结局指标
主要结局
maximum tolerated dose
时间窗: 1 year
This will be defined as the dose at which fewer than 1:6 patients experiences a dose-limiting toxicity.
次要结局
- local control rate(at 1 year and at 2 years)
- tolerability of adjuvant afatinib(at 3 months)
- median progression free survival(2 years)
- median overall survival(2 years)