INCLUSION CRITERIA:
Patients with histologically proven intracranial malignant glioma will be eligible for this protocol. Malignant glioma include glioblastoma multiforme (GBM), anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic mixed oligoastrocytoma (AMO), or malignant astrocytoma NOS (not otherwise specified).
Patients must have unequivocal evidence for tumor progression by MRI or CT scan. This scan should be performed within 14 days prior to registration and on a steroid dosage that has been stable for at least 5 days. If the steroid dose is increased between the date of imaging and registration a new baseline MR/CT is required. The same type of scan, i.e., MRI or CT must be used throughout the period of protocol treatment for tumor measurement.
Patients having undergone recent resection of recurrent or progressive tumor will be eligible as long as all of the following conditions apply:
a) They have recovered from the effects of surgery.
b) Residual disease following resection of recurrent tumor is not mandated for eligibility into the study. To best assess the extent of residual disease post-operatively, a CT/MRI should be done:
no later than 96 hours in the immediate post-operative period or;
at least 4 weeks post-operatively, and;
within 14 days of registration, and;
on a steroid dosage that has been stable for at least 5 days.
If the 96-hour scan is more than 21 days before registration, the scan needs to be repeated. If the steroid dose is increased between the date of imaging and registration, a new baseline MRI/CT is required on a stable steroid dosage for at least 5 days.
Patients must have failed prior radiation therapy and must have an interval of greater than or equal to 4 weeks from the completion of radiation therapy to study entry.
All patients must sign an informed consent, or if cognitively impaired, their assigned DPA, indicating that they are aware of the investigational nature of this study. Patients will designate a power of attorney.
Patients must be greater than or equal to 18 years old, and with a life expectancy greater than 8 weeks.
Patients must have a Karnofsky performance status of greater than or equal to 60.
Patients must have recovered from the toxic effects of prior therapy: 4 weeks from any investigational agent, 4 weeks from prior cytotoxic therapy, two weeks from vincristine, 6 weeks from nitrosoureas, 3 weeks from procarbazine administration, and 1 week from non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. (radiosensitizer does not count). Any questions related to the definition of non-cytotoxic agents should be directed by the Study Chair.
Patients must have adequate bone marrow function (ANC greater than 1,500/mm(3), platelet count of greater than or equal to 100,000/mm(3), and hemoglobin greater than or equal to 10 gm/dl), adequate liver function (SGOT and bilirubin less than 2 times ULN), and adequate renal function (serum creatinine less than 1.5 mg/dL otherwise a measured 24-hour creatinine clearance greater than or equal to 60 cc/min) before starting therapy. These tests must be performed within 14 days prior to registration. Eligibility level for hemoglobin may be reached by transfusion. Eligibility level for platelets may not be reached by transfusion.
Patients must not have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patients' ability to tolerate this therapy.
Patients must not have active infection requiring IV antibiotics.
Patients must not be pregnant or nursing, and all patients (both men and women) must be willing to practice birth control during and for 2 months after treatment with Talampanel. Women of childbearing potential (WCBP) must have a negative serum or urine pregnancy test. In addition, sexually active WCBP must agree to use two forms of adequate contraceptive methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner). Men should also protect their partner from becoming pregnant through use of condoms with spermicide, vasectomy or abstinence.
EXCLUSION CRITERIA:
Patients who, in the view of the treating physician, have significant active cardiac, hepatic, renal, or psychiatric diseases that would significantly increase the risk of using talampanel are ineligible.
No concurrent use of other standard chemotherapeutics or investigative agents.
Patients known to have an active, life-threatening malignancy, other than glioma.
Routine physical examination and baseline blood tests (CBC and platelets, SGOT, alkaline phosphatase, total and direct bilirubin, electrolytes, BUN, creatinine) and levels of any anti-epileptic agent the patient is taking that is routinely measured (phenytoin, valproate, carbamazepine, phenobarbitol).
A contrast-enhanced MRI scan (CT scan if patient is unable to undergo a MRI scan) of the head will be obtained within 2 weeks of registration).
Health-related Quality of Life (HRQL): HRQL will be assessed with the Functional Assessment of Cancer Therapy (FACT-Br). Administration of the FACT-Br within 2 weeks of trial entry. The FACT-Br is a reliable and valid questionnaire to assess health-related quality of life in patients with brain cancer. The questionnaire consists of 45 one-sentence statements and is organized into five sections where physical, social/family and functional subscales comprise of 7 statements, emotional subscale comprises of 6 statements, and brain tumor specific subscale comprises of 18 statements. The questionnaire is self-administered and filled in by patients. Patients rate the statements on 5 point rating scale where 0 equals not at all and 4 equals very much. In this study, the raw scoring will be used to calculate subscale domain scores as well as total summary score. Negatively stated items have to be reversed before calculation of the scores. A higher score represents a more favorable response. If there are less or equal 50% of data in the subscale missing (a minimum of 4 items answered), the subscale score will be prorated. If more than 50% of data in the subscale are missing, the scores cannot be calculated. If overall response rate for the 45 items is less or equal 80%, the scores cannot be calculated.
Warren Grant Magnuson Clinical Center (CC)