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

Clinical trial: Talampanel in Treating Patients With Recurrent High-Grade Glioma

Summary: RATIONALE: Drugs used in chemotherapy such as talampanel use different ways to stop tumor cells from dividing so they stop growing or die.
  PURPOSE: This phase II trial is studying how well talampanel works in treating patients with recurrent, progressive high-grade glioma.

Detailed description: OBJECTIVES:
  -  Determine the efficacy of talampanel, in terms of 6-month progression-free survival, in patients with recurrent high-grade gliomas.
  -  Determine, preliminarily, the toxic effects of this drug in these patients.
  -  Determine, preliminarily, the quality of life of patients treated with this drug.
  -  Determine the pharmacokinetics of this drug in patients who are and who are not receiving enzyme-inducing antiepileptic drugs.
  OUTLINE: Patients are stratified according to type of glioma (anaplastic astrocytoma vs glioblastoma multiforme). Patients in each stratum are assigned to 1 of 3 treatment groups according to concurrent enzyme-inducing antiepileptic drug use (yes, no, or valproic acid).
  Patients in each group receive different doses of oral talampanel 3 times daily on days 1-42. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.
  Quality of life is assessed at baseline, every 3 weeks during the first course, every 6 weeks before all subsequent courses, and then within 2 weeks of study completion.
  Patients are followed within 2 weeks.
  PROJECTED ACCRUAL: A total of 91 patients (50 with anaplastic astrocytoma and 41 with glioblastoma multiforme) will be accrued for this study within 1 year.

Eligibility: DISEASE CHARACTERISTICS:
  -  Histologically confirmed high-grade glioma, including any of the following:
  -  Glioblastoma multiforme
  -  Anaplastic astrocytoma
  -  Anaplastic oligodendroglioma
  -  Anaplastic mixed oligoastrocytoma
  -  Malignant astrocytoma not otherwise specified
  -  Patients with clinical and radiographic diagnosis of brain stem glioma are also eligible
  -  Evidence of tumor progression by MRI or CT scan
  -  Scan must be performed while patient is on a stable steroid dose for at least 5 days
  -  Must have failed prior radiotherapy
  -  Residual disease after prior resection of recurrent or progressive tumor is allowed
  PATIENT CHARACTERISTICS:
  Age
  -  18 and over
  Performance status
  -  Karnofsky 60-100%
  Life expectancy
  -  More than 8 weeks
  Hematopoietic
  -  Absolute neutrophil count greater than 1,500/mm^3
  -  Platelet count at least 100,000/mm^3 (transfusion independent)
  -  Hemoglobin at least 10 g/dL (transfusion allowed)
  Hepatic
  -  Bilirubin less than 2 times upper limit of normal (ULN)
  -  SGOT less than 2 times ULN
  -  No significant active hepatic disease
  Renal
  -  Creatinine less than 1.5 mg/dL OR
  -  Creatinine clearance at least 60 mL/min
  -  No significant active renal disease
  Cardiac
  -  No significant active cardiac disease
  Other
  -  Not pregnant or nursing
  -  Negative pregnancy test
  -  Fertile patients must use 2 effective methods of contraception during and for 2 months after study participation
  -  Able to swallow whole capsules
  -  No active infection requiring IV antibiotics
  -  No significant active psychiatric disease that would preclude use of the study drug
  -  No other significant uncontrolled medical illness that would preclude study participation
  -  No other active life-threatening malignancy
  PRIOR CONCURRENT THERAPY:
  Biologic therapy
  -  At least 1 week since prior interferon or thalidomide
  -  No concurrent anticancer immunotherapy
  Chemotherapy
  -  At least 2 weeks since prior vincristine
  -  At least 3 weeks since prior procarbazine
  -  At least 6 weeks since prior nitrosoureas
  -  No other concurrent anticancer chemotherapy
  Endocrine therapy
  -  See Disease Characteristics
  -  At least 1 week since prior tamoxifen
  -  Concurrent steroids for the control of increased intracranial pressure allowed
  Radiotherapy
  -  See Disease Characteristics
  -  At least 4 weeks since prior radiotherapy
  -  No concurrent anticancer radiotherapy
  Surgery
  -  See Disease Characteristics
  -  Prior recent resection of recurrent or progressive disease allowed
  Other
  -  Recovered from all prior therapy
  -  At least 1 week since prior noncytotoxic agents (e.g., isotretinoin), except for radiosensitizers
  -  At least 4 weeks since prior investigational agents
  -  At least 4 weeks since prior cytotoxic therapy
  -  No other concurrent investigational agents

Relevance to patient case: not relevant