PTK is an investigational new drug that has been shown in early laboratory studies to prevent the formation of new blood vessels that allow the tumor to grow. These studies have shown that the study drug can potentially improve the effectiveness of additional radiation and chemotherapy. With this study, we would like to examine the effects of PTK when used in combination with radiation therapy and the anti-cancer drug temozolomide, the standard treatment for patients with newly diagnosed glioblastoma. We would also like to learn how the study drug is absorbed, distributed, and cleared from the body.

• Since we are looking for the highest dose of PTK that can be administered safely without severe or unmanageable side effects, not everyone who participates will get the same dose of PTK. A small group will be enrolled onto the study and given a certain dose. If they tolerate it well, the next small group enrolled will receive a higher dose. This will continue until the highest dose that can be given without severe or unmanageable side effects is found.
• Participants will receive PTK twice daily along with temozolomide daily during each treatment cycle. Each treatment cycle lasts 28 days.
• PTK will start on Day 0 of the first cycle and will be given twice daily for the 7 weeks the participant receives radiation therapy.
• Daily doses of temozolomide will begin on Day of the first cycle and continue until the last dose of radiation therapy in cycle 1.
• Each participant will receive 7 weeks of radiation therapy. Radiation therapy will start on Day 5 of the first cycle and will be administered monday through friday, except on holidays.
• When radiation stops, temozolomide and PTK will be given for a maximum of 6 post-radiation cycles of study treatment. During these cycles, PTK and temozolomide will be given for 5 consecutive days followed by 23 days of no drugs.
• Tests will be performed routinely throughout the study treatment and include; chest x-rays, blood tests, physical exams, urine tests and ECG.
• The following procedures will be performed at the end of the study or after the participants last dose of study medication; tumor assessment by MRI, routine blood draws, neurological/physical exam and, medical history review.

Inclusion Criteria:

• All patients must have histologically verified glioblastoma. Patients mus have paraffin blocks of tumor that must be sent for analysis.
• 18 years of age or older
• Karnofsky Performance Status greater than or equal to 60
• Adequate laboratory values as described by the protocol
• Life expectancy of greater than 12 weeks
• Patient must be able to undergo serial MR imaging
• Patients must be on an enzyme-inducing anti-epileptic drug(s) as listed in the protocol
• No steroids or a stable dose of steroids for at least 5 days or a decreasing dose
• Mini-mental status examination of 15 or greater

Exclusion Criteria:

• Pregnant or breast-feeding women
• Concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast
• Prior chemotherapy or cranial radiation therapy for glioblastoma
• Prior biologic or immunotherapy less than 2 weeks prior to registration
• If the patient surgery is more than 16 days or less than 13 days from the start of PTK787/ZK 222854
• Prior therapy with anti-VEGF agents
• Pleural effusion or ascites that causes respiratory compromise
• Concurrent severe and/or uncontrolled medical conditions which could compromise participation is the study
• Impairment of gastrointestinal function or GI disease that may significantly alter the absorption of PTK787/ZK 222584
• Confirmed diagnosis of human immunodeficiency virus (IV)
• Patients who are taking therapeutic warfarin sodium or other anticoagulants or anti-platelet agents
• Patients requiring aprepitant, dolasetron, and tropisetron as antiemetics are excluded