EValuation of Erlotinib as a Neoadjuvant Therapy in Stage III NSCLC Patients With EGFR Mutations (EVENT Trial)
EValuation of Erlotinib as a Neoadjuvant Therapy in Stage III NSCLC Patients With EGFR Mutations (EVENT Trial)
This phase II trial studies how well erlotinib hydrochloride works before surgery in treating patients with stage III non-small cell lung cancer. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving erlotinib hydrochloride before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
PRIMARY OBJECTIVES:
I. To estimate the rate of mediastinal nodal clearance and complete pathological response after neoadjuvant erlotinib (erlotinib hydrochloride) in patients with epidermal growth factor receptor (EGFR) mutated stage III non-small cell lung cancer (NSCLC).
SECONDARY OBJECTIVES:
I. To determine the progression free survival in patient population of EGFR mutated stage III NSCLC patients who are treated with neoadjuvant erlotinib therapy.
II. To determine the overall survival. III. To estimate the overall response rate from neoadjuvant erlotinib. IV. To estimate the surgical resection rate. V. To evaluate the safety of neoadjuvant erlotinib.
TERTIARY OBJECTIVES:
I. To determine several molecular and cellular biomarkers in the tumors, the skin and the serum that are predictive of the efficacy of neoadjuvant erlotinib.
OUTLINE:
Patients receive erlotinib hydrochloride orally (PO) once daily (QD) for 2 months and then undergo thoracotomy.
After completion of study treatment, patients are followed up at 30 days, every 3 months for 1 year, and then every 6 months for 5 years.
Inclusion Criteria:
Pathologically proven (either histologic or cytologic) diagnosis of stage IIIA or IIIB non-small cell lung cancer; (according to American Joint Committee on Cancer [AJCC] staging, 7th edition) within 4 weeks of registration; the patient should have histologically or cytologically confirmed N2 disease
Activating mutation in EGFR
No prior chemotherapy or radiation for lung cancer
Patients may be potentially resectable or unresectable
Stage III A or B disease, including no distant metastases- based on following diagnostic workup:
Patients must have measurable or evaluable disease
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Absolute neutrophil count (ANC) >= 1,500 cells/ul
Platelets >= 100,000 cells/ul
Hemoglobin >= 9.0 g/dl (note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= g/dl is acceptable)
Serum creatinine =< 1.5 x upper limit of normal (ULN)
Total bilirubin < 2.0 times the institutional upper limit of normal (ULN)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x the ULN
Women of childbearing potential must have:
Ability to take oral medication
Patient must sign study specific informed consent prior to study entry
Exclusion Criteria:
Pleural or pericardial effusion
Severe, active co-morbidity, defined as follows:
Cardiac symptoms; any of the following should be considered for exclusion:
History of significant bleeding disorder unrelated to cancer, including:
Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness
Men and women who:
Are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 4 weeks after cessation of study drug, or women who: