VNP40101M and Temozolomide in Treating Patients With Progressive or Relapsed Malignant Glioma

DISEASE CHARACTERISTICS:

Inclusion criteria:

• Histologically proven malignant glioma including any of the following:

  • Glioblastoma multiforme
  • Gliosarcoma
  • Anaplastic astrocytoma
  • Anaplastic oligodendroglioma
  • Anaplastic mixed oligoastrocytoma
  • Malignant astrocytoma not otherwise specified
• Unequivocal evidence of tumor recurrence or progression by MRI or CT scan with contrast
• No more than one relapse

• Patients having undergone recent resection of recurrent or progressive tumor will be eligible as long as all of the following conditions apply:

  • More than 2 weeks from surgery and have recovered from the effects of surgery
  • Evaluable or measurable disease following resection of recurrent tumor is not mandated for eligibility into the study if a treatment failure can be evaluated

  • Enhanced CT scan/ MRI should be done no later than 96 hours in the immediate post-operative period or 4-6 weeks post-operatively

    • If the 96-hour scan is more than 2 weeks from registration, the scan needs to be repeated
    • A baseline scan should be performed within 14 days prior to registration and on a steroid dosage that has been stable for 5 or more days otherwise a new baseline MRI/CT is required
    • The same type of scan (i.e., MRI or CT scan) must be used throughout the period of protocol treatment for tumor measurement
• Must have failed prior external-beam radiotherapy
• Must have failed one prior systemic treatment with chemotherapy or biologic agents

PATIENT CHARACTERISTICS:

Inclusion criteria:

• Karnofsky performance status 60-100%
• Life expectancy > 12 weeks
• WBC > 3,000/mm³
• ANC > 1,500/mm³
• Platelet count > 100,000/mm³
• Hemoglobin > 10 mg/dL
• AST and ALT < 4 times upper limit of normal (ULN)
• Bilirubin < 2 times ULN
• Creatinine < 1.5 times ULN
• Fertile patients must use acceptable contraceptive methods (abstinence, intrauterine device [IUD], oral contraceptive or double barrier device)
• Negative pregnancy test
• Not pregnant or nursing

Exclusion criteria:

• Active uncontrolled bleeding
• Active infection of any kind
• Unwilling or unable to follow protocol requirements or to give informed consent

• Active heart disease including any of the following:

  • Myocardial infarction within the past 3 months
  • Uncontrolled arrhythmias
  • Uncontrolled coronary artery disease
  • Uncontrolled congestive heart failure
• Known HIV-positive patients (HIV testing is not required)
• History of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix) unless in complete remission and off all therapy for that disease for a minimum of 3 years

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

• See Disease Characteristics
• Recovered from prior therapy
• At least 2 weeks since prior vincristine
• More than 4 weeks since prior cytotoxic therapy (6 weeks for nitrosoureas)
• More than 4 weeks since prior radiotherapy
• More than 4 weeks since prior experimental biologic agents (e.g., EGFR inhibitors, etc)
• More than 3 weeks since prior procarbazine administration

• More than 2 weeks since prior non-cytotoxic agents (e.g., interferon, tamoxifen, thalidomide, or isotretinoin)

  • Radiosensitizer does not count

• At least 2 weeks since prior and no concurrent enzyme inducing anticonvulsants

  • If patient is on an enzyme inducing anticonvulsant, they may be converted to a non-enzyme inducing anticonvulsant

Exclusion criteria:

• Any other concurrent standard or investigational treatment for cancer, or any other investigational agent for any indication
• Concurrent disulfiram