• Survival at 52 weeks [ Designated as safety issue: No ]
  

• Time- to-disease progression [ Designated as safety issue: No ]
  
• Toxicity [ Designated as safety issue: Yes ]
  

OBJECTIVES:

Pilot study

• Determine the maximum tolerated dose of erlotinib administered with temozolomide and radiotherapy in patients with glioblastoma multiforme or other grade 4 brain tumors who are currently on enzyme-inducing anticonvulsant (EIAC) therapy vs no EIAC therapy.
• Determine the safety and tolerability of this regimen in these patients.
• Determine the toxic effects of this regimen in these patients.
• Determine the efficacy of this regimen, in terms of 1-year survival, in these patients.

Phase II

• Determine the response rate and time to progression in patients treated with this regimen.
• Determine the 6-month progression-free survival of patients treated with this regimen.
• Determine the toxic effects of this regimen in these patients.

OUTLINE: This is a multicenter, dose-escalation pilot study of erlotinib followed by a phase II study. Patients are stratified according to concurrent enzyme-inducing anticonvulsant drug use (yes vs no).

• Pilot study: Patients receive oral erlotinib once daily. After 1 week of erlotinib alone, patients also receive oral temozolomide once daily for 6 weeks and undergo concurrent radiotherapy 5 days a week for 6 weeks. After completion of radiotherapy, patients continue to receive erlotinib once daily alone in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of radiotherapy, patients also receive oral temozolomide once daily for 5 days. Temozolomide treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity .

Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

• Phase II: Once the MTD of erlotinib is determined, additional patients are treated with erlotinib at the MTD, temozolomide, and radiotherapy as above.

Patients are followed every 3 months for 5 years and then annually for 10 years.

PROJECTED ACCRUAL: A total of 12-78 patients (6-36 not receiving concurrent enzyme-inducing anticonvulsant drugs [EIADs] and 6-42 receiving concurrent EIADs) will be accrued for the pilot portion of this study within 4-12 months. A total of 93 patients will be accrued for the phase II portion of this study within 11 months.

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy:

• At least 6 months

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin ≥ 9 g/dL

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST no greater than 2.5 times ULN

Renal:

• Creatinine no greater than 1.5 times ULN

Cardiovascular:

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Gastrointestinal:

• No inability to take oral medications
• No requirement for IV alimentation
• No active uncontrolled peptic ulcer disease

Ophthalmic:

• 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)

Other:

• 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

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy for any brain tumor
• No prior temozolomide

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy for any brain tumor

Surgery:

• See Disease Characteristics
• More than 21 days since prior major surgery (excluding neurosurgical biopsy or brain tumor resection)
• No prior surgical procedures affecting absorption

Other:

• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent warfarin
• No other concurrent investigational agents