Dose-Intense Temozolomide in Recurrent Glioblastoma
Condition: Glioblastoma; Gliosarcoma
MeSH terms: Glioblastoma; Gliosarcoma
Intervention: Temozolomide
Intervention description: Taken orally daily for the first three weeks of a four-week cycle.
Intervention MeSH terms: Temozolomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 58.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: recurrent glioblastoma; temodar; temozolomide

Summary:

      Temozolomide (Temodar) is an FDA approved medication for the treatment of newly diagnosed
      glioblastomas. In this study, we will be using temozolomide to treat recurrent glioblastomas.
      We will be using a different dose and schedule than the FDA approved dose and schedule. The
      purpose of this study is to determine if patients that have failed standard temozolomide
      treatment will respond to temozolomide when given at a different dose and schedule (21 days
      every 28 days).
    

Eligibility criteria:

        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