A randomized, open-label, 3-arm Phase II study assessing the anti-tumor activity of BIBW 2992 among patients with recurrent GBM. Eligible patients will be randomly assigned in a 1:1:1 manner to one of the following three arms:

Arm 1: Daily temozolomide (TMZ) administered for 21 days (continuous oral dosing), followed by 7 days off (TMZ 21/7). TMZ will be dosed at 75 mg/m2.

Arm 2: Daily BIBW 2992 (administered at 50 mg/day continuous oral dosing).

Arm 3: TMZ 21/7 plus BIBW 2992. TMZ will be dosed at 75 mg/m2. BIBW 2992 will be administered at the MTD as determined in the Phase I part as continuous, daily oral dosing.

Subjects may remain on there assigned treatment group and get additional cycles as long as their cancer has not progress and they are tolerating treatment. Study medication will be dispersed during the follow-up visit on day 1 of each new cycle. Adverse events will be captured and safety labs will also be collected during follow-up visits.

• Histologically-confirmed GBM at first episode of recurrence after prior combined chemoradiotherapy.
• Bi-dimensionally measurable disease with a minimum measurement of 1 cm (10 mm) in one diameter on MRI performed within 14 days prior to first treatment.
• Age =18 years at entry.
• Karnofsky Performance Score (KPS) =70.

• Less than 12 weeks between radiotherapy and the start of study treatment.
• Less than two weeks from surgical resection (one week from prior stereotactic biopsy).
• Less than two weeks after previous chemotherapy (6 weeks from nitrosureas).
• Less than four weeks from prior treatment with bevacizumab.
• Participation in another clinical study within the past 2 weeks before start of therapy or concomitant with this study.
• Progressive disease or toxicity =CTCAEv3 Grade 3 to protracted temozolomide dosing (defined as temozolomide administered more than 5 days/28 day cycle).
• Pregnancy or breast-feeding.