Enzastaurin and Temozolomide in Treating Patients With Primary Gliomas

DISEASE CHARACTERISTICS:

• Histologically confirmed primary supratentorial glioma

  • WHO histologic grade 3 or 4

    • Patients who have undergone prior treatment for low-grade glioma that has transformed to glioblastoma (biopsy proven) allowed
• Amenable to standard temozolomide treatment
• First or second recurrent disease after prior surgery and/or radiotherapy OR newly diagnosed disease that is not amenable to radiotherapy (e.g., multifocal disease)

PATIENT CHARACTERISTICS:

• ECOG or WHO performance status 0-2
• Hemoglobin ≥ 10.0 g/dL
• Neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Bilirubin ≤ 1.5 x upper limit of normal (ULN)
• Alkaline phosphatase and transaminases ≤ 2.5 x ULN
• Serum creatinine < 1.7 mg/dL
• Not pregnant or lactating
• Negative pregnancy test
• Fertile patients must use effective contraception
• Clinically normal cardiac function
• No ischemic heart disease within the past 6 months
• No clinically significant abnormalities or uncontrolled cardiac arrhythmia by ECG
• QTc interval ≤ 450 msec (males) or ≤ 470 msec (females) by baseline 12-lead ECG
• No history of congenital long QTc syndrome
• No history of stroke
• No other prior or concurrent malignancy within the past 5 years except cone biopsied carcinoma of the cervix or adequately treated basal or squamous cell skin carcinoma
• No unstable systemic diseases
• No active uncontrolled infections
• No uncontrolled hypertension
• No psychological, familial, sociological, or geographical condition that would preclude study participation
• Must be able to swallow tablets

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No more than 1 prior chemotherapy regimen in the adjuvant setting or for first recurrence
• Prior temozolomide allowed provided there was no disease progression during temozolomide treatment or within 6 weeks of completing temozolomide treatment
• Prior surgery for primary brain tumor within the past 3 months allowed
• Patients who are receiving corticosteroid treatment must be on a stable or decreasing dose for at least 1 week before study entry
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)

• At least 14 days since prior and no concurrent enzyme-inducing antiepileptic drugs including, but not limited to, any of the following:

  • Phenytoin
  • Carbamazepine
  • Phenobarbital
• More than 30 days since prior and no other concurrent investigational treatments

• No concurrent anticoagulant treatment (e.g., warfarin)

  • Low molecular weight heparin for patients who require anticoagulant therapy after starting study treatment may be allowed
• No concurrent routine use of colony-stimulating factors
• No other concurrent anticancer agents