Inclusion Criteria:

• 18 years of age or older
• Histologically confirmed diagnosis of a recurrent primary WHO grade IV malignant glioma (glioblastoma). Patients with recurrent disease whose diagnostic pathology confirmed glioblastoma will not need re-biopsy. Patients with prior low-grade glioma or anaplastic glioma are eligible if histologic assessment demonstrates transformation to GBM.
• Evidence of EGFR gene amplification by fluorescence in situ hybridization (FISH) in archival tumor material.
• Patients must have at least 15 unstained slides or 1 tissue block (frozen or paraffin embedded) available from a prior biopsy or surgery.
• For Arm A: patients must be at first recurrence of GBM, must not have had previous anti-VEGF therapy, and must be candidates for surgical partial or gross-total resection.
• For Arm B: patients must be at first recurrence of GBM and must not have had prior anti-VEGF therapy.
• For Arm C: patients may have had an unlimited number of prior therapies for GBM, however must be at first recurrence from a therapeutic regimen containing bevacizumab
• Progressive disease on contrast-enhanced brain CT or MRI as defined by McDonald Criteria, or have documented recurrent glioblastoma on diagnostic biopsy.
• Prior to enrollment, there must be an interval of at least 2 weeks between prior surgical resection (1 week for intracranial biopsy) and adequate wound healing.
• Interval of at least 12 weeks from prior radiotherapy unless there is either: a) histopathologic confirmation of recurrent tumor, or b) new enhancement on MRI outside of XRT treatment field.
• Patients must have sufficient time to recover from prior therapy.
• Karnofsky Performance Score 70% or greater
• Adequate hematologic and liver function as outlined in the protocol
• Creatinine within normal institutional limits
• Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation and for at least 3 months thereafter.

Exclusion Criteria:

• Presence of extra-cranial metastatic disease
• Participants may not be receiving any other investigational agents
• Prior investigational therapy with an agent that is known or proposed to be active by action on any component of the EGFR tyrosine kinase, IGF1R, mTor, orc-MET pathways
• Patients who have been previously treated with an anti-VEGF agent will be excluded from Arm A and Arm B.
• Patients must not have received prior Gliadel wafers
• For participants in Arm A, if the diagnostic pathology of the biopsy specimen is not consistent with recurrent glioblastoma, then the participant must be taken off study and be replaced with another participant that meets the inclusion criteria and is eligible for surgical resection.
• Any surgery (not including minor diagnostic procedures such as lymph node biopsy) within 2 weeks of baseline disease assessments; or not fully recovered from any side effects of previous procedures.
• Any clinically significant gastrointestinal abnormalities, which may impair intake, transit or absorption of the study drug.
• Any psychiatric or cognitive disorder that would limit the understanding or rendering of informed consent and/or compromise compliance with the requirements of this protocol
• Patients with known interstitial lung disease
• Uncontrolled or significant cardiovascular disease
• Any patient with a history of significant cardiovascular disease, even if currently controlled, or who has signs or symptoms suggesting impaired left ventricular function in the judgment of the investigator must have a screening left ventricular ejection fraction evaluation by ECHO or MUGA. Patients with LVEF measurements below local institutional lower limit of normal or less then 50% will not be eligible.
• Individuals with a history of a different malignancy are ineligible except for the circumstances outlined in the protocol
• Patients who have had prior stereotactic radiotherapy, convection enhanced delivery or brachytherapy as gliosis/scarring from these modalities may limit delivery
• Patients will not be eligible if they present with leptomeningeal dissemination
• Pregnant women
• HIV-positive individuals on combination antiretroviral therapy are ineligible
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to PF-00299804
• Other severe acute or chronic medical condition, uncontrolled intercurrent illness or laboratory abnormality that may increase the risk associated with trial participation or investigation product administration or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the patient inappropriate for entry into this trial.