Patient case: 84-year-old male with glioblastoma; genetic feature: CDK6

Clinical trial: Chemotherapy in Treating Patients With Progressive or Recurrent Brain Tumors

Summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.
  PURPOSE: Phase I/II trial to study the effectiveness of irofulven in treating patients who have progressive or recurrent astrocytoma, oligodendroglioma, or glioblastoma multiforme.

Detailed description: OBJECTIVES:
  -  Determine the maximum tolerated dose (MTD) of irofulven alone or combined with anticonvulsants known to be metabolized by cytochrome P450 in patients with progressive or recurrent high-grade anaplastic astrocytoma, anaplastic oligodendroglioma, or glioblastoma multiforme.
  -  Assess the pharmacokinetics of this drug on this schedule and determine the effects of P450-inducing anticonvulsants on the pharmacokinetics in these patients.
  -  Determine the response rate of patients treated with this drug administered at the MTD.
  -  Determine the duration of progression-free survival and overall survival of patients treated with this drug.
  -  Determine the toxic effects of this drug in these patients.
  OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to concurrent use of anticonvulsant drugs that induce cytochrome P450 (yes vs no drugs or modest-induction drugs).
  Patients receive irofulven IV over 30 minutes on days 1-4 or 1-5 (depending on dose-escalation level). Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
  Cohorts of 3-6 patients (per stratum) receive escalating doses of irofulven until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are accrued to receive treatment with irofulven at the recommended phase II dose.
  Patients are followed at 1 week and then every 2 months thereafter.
  PROJECTED ACCRUAL: Approximately 18 patients (9 per stratum) will be accrued for the phase I portion of the study. Approximately 17-35 patients will be accrued for the phase II portion of the study within 6-12 months.

Eligibility: DISEASE CHARACTERISTICS:
  -  Histologically proven malignant high-grade glioma that is progressive or recurrent after radiotherapy and/or chemotherapy
  -  Anaplastic astrocytoma
  -  Anaplastic oligodendroglioma
  -  Glioblastoma multiforme
  -  Prior low-grade glioma that has progressed to high-grade glioma after radiotherapy and/or chemotherapy allowed
  -  Measurable disease by MRI or CT scan
  PATIENT CHARACTERISTICS:
  Age:
  -  18 and over
  Performance status:
  -  Karnofsky 60-100%
  Life expectancy:
  -  Not specified
  Hematopoietic:
  -  Absolute neutrophil count at least 1,500/mm^3
  -  Platelet count at least 100,000/mm^3
  Hepatic:
  -  Bilirubin no greater than 1.5 mg/dL
  -  Transaminases no greater than 2.5 times upper limit of normal
  Renal:
  -  Creatinine no greater than 1.5 mg/dL
  Other:
  -  Not pregnant or nursing
  -  Negative pregnancy test
  -  Fertile patients must use effective contraception
  -  No serious concurrent infection or medical illness that would preclude study therapy
  -  No other prior malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast
  -  Mini mental score at least 15
  PRIOR CONCURRENT THERAPY:
  Biologic therapy:
  -  Not specified
  Chemotherapy:
  -  See Disease Characteristics
  -  No more than 2 prior chemotherapy regimens
  -  At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered
  Endocrine therapy:
  -  Maintained on a stable corticosteroid regimen for at least 5 days before and during study
  Radiotherapy:
  -  See Disease Characteristics
  -  At least 3 months since prior radiotherapy and recovered
  Surgery:
  -  Recovered from prior surgery
  Other:
  -  No other concurrent investigational agents

Relevance to patient case: not relevant