A Study of the Safety and Efficacy of Tarceva in Patients With First Relapse of Grade IV Glioma (Glioblastoma Multiforme)

Inclusion Criteria:

* Signed informed consent
* Age \>= 18 years
* Histologically confirmed GBM in first relapse
* Disease progression in those patients following prior implantation with Gliadel(R) wafer(s) (polifeprosan 20 with carmustine implant) must be confirmed by biopsy. Prior therapy with Gliadel(R) is allowed only as a component of primary surgery. Patients with Gliadel(R) implants after a secondary resection are not eligible.
* Radiographic evidence of disease progression, as assessed by the investigator, on magnetic resonance imaging (MRI) or CT scan
* Bi-dimensionally measurable disease with a minimum measurement of 1 cm on MRI or CT scan performed within 14 days prior to study entry
* Prior radiotherapy
* Availability of tissue to allow central confirmation of GBM diagnosis (all original slides are preferred)
* Availability of paraffin blocks or slides to allow determination of EGFR amplification status
* Recovery from the toxic effects of a prior therapy, including 4 weeks from prior cytotoxic agents (except 6 weeks from prior nitrosoureas, 3 weeks from prior procarbazine administration, 2 weeks from prior vincristine, or 3 weeks from irinotecan \[CPT-11\] when given on a weekly schedule), 4 weeks from any prior investigational agent, and 1 week from prior non-cytotoxic agents (e.g., interferon, tamoxifen, thalidomide, 13-cis-retinoic acid, etc.)
* If receiving corticosteroids, patients must be on a stable, non-increasing dose of corticosteroids for \>= 2 weeks prior to baseline MRI scan
* ECOG performance status of 0 or 1
* Life expectancy \> 12 weeks
* Use of an effective means of contraception in males and in females of childbearing potential
* Ability to comply with study and follow-up procedures If the decision is made at the end of Stage 1 to enroll patients with tumors known to be positive for EGFR amplification, the following additional inclusion criteria will be applied: Confirmation of diagnosis; Confirmation of positive EGFR amplification status

Exclusion Criteria:

* Prior treatment with Gleevec (e.g., imatinib mesylate) or agents directed at EGFR (e.g., Iressa)
* Prior treatment with Gliadel(R) following second (salvage or debulking) therapy
* History of any other malignancy within 5 years (except non-melanoma skin cancer or carcinoma in situ of the cervix)
* More than one prior chemotherapy regimen
* ANC \< 1500/uL
* Platelets \< 100,000/uL
* Total bilirubin \> 1.6 mg/dL
* AST/ALT \>= 2.5 x upper limit of normal (ULN)
* Creatinine \> 1.5 x ULN
* Pregnant or nursing females
* Unstable systemic disease, including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, or myocardial infarction within 6 months prior to study entry, or serious cardiac arrhythmia requiring medication
* Major surgical procedure 2 weeks prior to study entry or anticipation of need for major surgical procedure during the course of the study
* Inability to take oral medication