A Phase I/II Study of OSI-774 and Temozolomide In Combination With Radiation Therapy In Glioblastoma Multiforme

Inclusion Criteria:

- Histologically confirmed diagnosis of 1 of the following:

- Glioblastoma multiforme (grade 4 astrocytoma)

- Gliosarcomas

- Other grade 4 astrocytoma variants (e.g., giant cell)

- Must be enrolled at least 1 week, but no more than 4 weeks, after prior biopsy or
surgery

- Performance status - ECOG 0-2

- Performance status - Karnofsky 60-100%

- At least 6 months

- Absolute neutrophil count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

- Hemoglobin ≥ 9 g/dL

- Total bilirubin ≤ upper limit of normal (ULN)

- AST no greater than 2.5 times ULN

- Creatinine no greater than 1.5 times ULN

- No symptomatic congestive heart failure

- No unstable angina pectoris

- No cardiac arrhythmia

- No inability to take oral medications

- No requirement for IV alimentation

- No active uncontrolled peptic ulcer disease

- No abnormalities of the cornea (e.g., dry eye syndrome or Sjögren's syndrome)

- No congenital abnormality (e.g., Fuch's dystrophy)

- No abnormal slit-lamp examination using a vital dye (e.g., fluorescein or
Bengal-Rose)

- No abnormal corneal sensitivity test (e.g., Schirmer test or similar tear production
test)

- No prior allergy or intolerance to dacarbazine

- No other active malignancy requiring treatment

- No other concurrent uncontrolled illness

- No ongoing or active infection

- No psychiatric illness or social situation that would preclude study compliance

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No prior chemotherapy for any brain tumor

- No prior temozolomide

- No prior radiotherapy for any brain tumor

- No other concurrent investigational agents

- More than 21 days since prior major surgery (excluding neurosurgical biopsy or brain
tumor resection)

- No prior surgical procedures affecting absorption

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No concurrent warfarin