A Dose-Finding Study Of Afatinib In Combination With Cisplatin Or Carboplatin + Pemetrexed In Patients With EGFR-Mutant Lung Cancers Undergoing Definitive Chemoradiation

Inclusion Criteria:

- 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

Exclusion Criteria:

- 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