Dose-Intense Temozolomide in Recurrent Glioblastoma

• Participants will be given a medication-dosing calendar for each treatment cycle. Each treatment cycle lasts 4 weeks (28 days) during which time they will be taking temozolomide orally once a day for the first three weeks.
• At the end of each cycle (day 28, +/- 2 days), the following procedures will be performed: Complete physical examination including a neurological exam; vital signs; a review of current medications and symptoms; blood samples; a pregnancy test for women of child-bearing potential; self-administered quality of life questionnaire; brain MRI or CT scan.
• Participants may continue taking temozolomide until their tumor grows or if they experience unacceptable side effects.

Inclusion criteria

• Must provide independent consent or must demonstrate willingness to participate in the study and to adhere to dose and visit schedules.
• 18 years of age or older (of either sex, and of any race)
• Histologic diagnosis of GBM or gliosarcoma with an unequivocal progression by MRI or CT scan
• Must have received standard combined modality therapy as first-line treatment consisting of RT plus concomitant temozolomide followed by adjuvant temozolomide (at least 2 cycles of adjuvant temozolomide)
• Gadolinium MRI or contrast CT scan must be obtained within 14 days prior to registration, and must be on a steroid dose that has been stable for at least 5 days.
• Karnofsky Performance status of 60 or greater
• Life expectancy of at least 8 weeks
• Recovered from the toxic effects of prior therapy, and 21 days must have elapsed since prior treatment with temozolomide

o If a patient has residual toxicity from any previous treatment, toxicity must be ≤ Grade 1

• Laboratory tests within parameters outlined in the protocol
• Female subjects of childbearing potential & male subjects with female partner of childbearing potential must agree to use a medically accepted method of contraception or be surgically sterilized prior to Screening, while receiving protocol-specified medication, and for 30 days after stopping the study medication
• Negative pregnancy test within 48 hours prior to dosing with the study drug (for female subjects of childbearing potential)
• Free of any clinically relevant disease that would, in the Principal Investigator's opinion, interfere with the conduct of the study or study evaluations
• Must be able to adhere to the dosing and visit schedules, and agree to record medication times, concomitant medications, and adverse events (AEs) accurately and consistently in a daily diary
• Unstained slides (at least 15 of 10 micron thickness, or 20 when < 10 micron thickness)or 1 tissue block must be available from the original diagnostic biopsy/surgery or from the biopsy/surgery recurrence
• Participants who have undergone recent resection of recurrent or progressive tumor will be eligible provided at least 2 weeks has elapsed since surgery, and subjects have recovered from surgical-related trauma
• Residual disease following resection of recurrent GBM or gliosarcoma is not mandated for eligibility into the study.

Exclusion criteria

• Participant has received a dosing schedule of temozolomide other than 75 mg/m2/day for 42 days during RT followed by adjuvant temozolomide at a dose of 150-200 mg/m2/day for 5 days of a 28-day schedule (standard dose adjustments for toxicity are allowed)
• Any other anti-tumor agent other than standard surgical resection, RT and temozolomide prior to enrollment or during the study period
• Received treatment with BCNU (Gliadel) wafers or GliaSite
• Progressed prior to receiving at least 2 cycles of adjuvant temozolomide
• Pregnant or intending to become pregnant during the study
• In a situation or condition that, in the opinion of the Investigator, may interfere with optimal participation in the study
• Participating in any other clinical study in which an investigational drug is prescribed
• Allergic to or has sensitivity to the study drug or its excipients
• History of any other cancer (except non-melanoma skin cancer or carcinoma in situ of the cervix), unless he/she is in complete remission and has not received treatment for that particular disease for the past 3 or more years