Phase I Trial of R115777 With Radiation Therapy and Temozolomide in Patients With Newly Diagnosed Glioblastoma Multiforme
I. Establish MTD for R115777 in combination with Temozolomide with radiation in patients not
II. To define the safety of R115777 in combination with Temozolomide with radiation in this
III. To assess for evidence of antitumor activity in this patient population.
OUTLINE: This is a multicenter, dose-escalation study of tipifarnib. Patients are stratified
according to concurrent use of enzyme-inducing antiepileptic drugs (yes [closed to accrual
as of 3/15/05] vs no).
COMBINATION THERAPY: Patients receive oral tipifarnib twice daily on days 1-21. Courses
repeat every 28 days in the absence of disease progression or unacceptable toxicity. Within
5-9 days after beginning tipifarnib, patients receive oral temozolomide once daily for 6
weeks and concurrently undergo partial brain radiotherapy daily 5 days a week for 6 weeks.
After completion of radiotherapy, patients proceed to adjuvant therapy.
Cohorts of 3-6 patients receive escalating doses of tipifarnib until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2
of 3 or 2 of 6 patients experience dose-limiting toxicity. An additional 10 patients are
treated at the MTD.
ADJUVANT THERAPY: Patients continue to receive tipifarnib as above. With the initiation of
the next planned course of tipifarnib, patients receive oral temozolomide on days 1-5.
Treatment repeats every 28 days for 12 courses OR 1 year (whichever is longer) in the
absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients with progressive disease are followed at 10
weeks and then every 4 months. Patients who complete therapy are followed every 2 months for
1 year, every 3 months for 1 year, every 4 months for 1 year, and then every 6 months
thereafter until disease progression.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD of tipifarnib
Safety variables will be summarized by descriptive statistics. Adverse events that occur will be reported for each dose level and described in terms of incidence and severity. Laboratory data will be presented by dose level at each observation time. Values outside of normal limits will be identified and their frequency calculated. Parameters will be described based on the CTCAE severity grading. Distribution by CTCAE severity grade (when applicable) and clinical relevance will be given.
National Cancer Institute (NCI)
United States: Food and Drug Administration
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