Background: Recurrent GBM has a very poor prognosis and there is an unmet need for new treatment options. EGFR is an attractive therapeutic target for GBM, due to high rates of amplifcation and the growing evidence linking the activation of the EGFR and tumor proliferation, survival, angiogenesis and invasion. Amplification of EGFR is reported in approximately 50% of GBM and approximately 50% of these cases are associated with deletion of the extracellular ligand binding domain, the constitutively active mutant protein EGFRvIII. Dacomitinib (DA) is a second-generation, oral, irreversible, pan-HER tyrosine kinase inhibitor active in erlotinib and gefitinib-resistant nonclinical models of lung cancer. Methods: This multicenter, 2-stage, open-label, phase II trial aims to assess the efficacy and safety of DA in pts with recurrent GBM with EGFR gene amplification with or without EGFRvIII mutation. DA will be administered orally at a dose of 45 mg/day, until disease progression, unacceptable adverse side effects or study end. Pts at first recurrence will be enrolled onto 1 of 2 cohorts that will be recruited and analysed independently. Cohort A will include patients who have EGFR gene amplification and EGFRvIII mutations. Cohort B will include patients who have EGFR gene amplification but no EGFRvIII mutations. The primary endpoint is progression-free survival at six months (PFS6m) according to RANO criteria and each cohort will follow a Simon´s 2-stage optimal design (P0 = 15% PFS6m; P1=35% PFS6m; a, b error = 0.1, 0.1). For each cohort, 17 patients will be accrued in the stage 1. Additional 15 patients per cohort will be enrolled in stage 2 if the predetermined PFS6m of at least 3 patients is met in that cohort in stage 1. Secondary endpoints include safety, response rate, OS, duration of response and changes in steroid use. In December 2011 the study protocol received institutional review board approval and in April 2012 the trial commenced enrolment in 12 Spanish institutions members of GEINO.