Phase I/II Trial of R115777 in Patients With Recurrent Malignant Glioma
- Determine the maximum tolerated dose of tipifarnib in patients with recurrent or
progressive malignant glioma receiving enzyme-inducing antiepileptic drugs. (Stratum II
in the phase I portion of this study closed to accrual effective 07/16/2001.) (Phase I
completed effective 10/2/2001.) (Phase II open only to patients requiring resection and
who provide surgical tissue samples [effective 3/13/2003].)
- Define the safety and pharmacokinetic profile of this drug in this patient population.
- Assess for evidence of antitumor activity of this drug in these patients.
- Assess for evidence of inhibition of farnesyl protein transferase (FTase) on peripheral
blood monocytes as a surrogate endpoint of effective biologic activity of this drug in
- Determine the efficacy of this drug as measured by 6-month progression-free survival
and objective tumor response in these patients.
- Evaluate further the safety profile of this drug in these patients.
- Correlate treatment response with inhibition of FTase in peripheral blood monocytes in
patients treated with this drug.
OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to
their pretreatment medications (not receiving enzyme-inducing antiepileptic drugs [EIAEDs]
vs receiving EIAEDs with or without steroids).
Patients receive oral tipifarnib twice daily on days 1-21. Courses repeat every 4 weeks in
the absence of unacceptable toxicity or disease progression.
- Phase I (completed 10/2/2001): Cohorts of 3-6 patients from stratum II receive
escalating doses of tipifarnib until the maximum tolerated dose (MTD) is determined.
The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients
experience dose-limiting toxicity. (Stratum II in the phase I portion of this study
closed to accrual effective 07/16/2001.)
- Phase II (open only to patients requiring resection and who provide surgical tissue
samples [effective 3/13/2003]): Once the MTD is determined, additional patients with
glioblastoma multiforme from stratum II are accrued to receive treatment with
tipifarnib at the recommended phase II dose.
Patients 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 until progression. Patients are then followed every 4
PROJECTED ACCRUAL: Approximately 30 patients (15 per stratum) will be accrued for the phase
I portion of this study within 10 months. (Stratum II in the phase I portion of this study
closed to accrual effective 07/16/2001.) (Phase I completed effective 10/2/2001.) A total of
24 patients with glioblastoma multiforme from stratum II will be accrued for the phase II
portion of this study. (Phase II open only to patients requiring resection and who provide
surgical tissue samples [effective 3/13/2003].)
Masking: Open Label, Primary Purpose: Treatment
Timothy F. Cloughesy, MD
Jonsson Comprehensive Cancer Center
United States: Federal Government
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|
|University of Texas - MD Anderson Cancer Center||Houston, Texas 77030-4009|
|University of Michigan Comprehensive Cancer Center||Ann Arbor, Michigan 48109-0752|
|Jonsson Comprehensive Cancer Center, UCLA||Los Angeles, California 90095-1781|
|University of Texas Health Science Center at San Antonio||San Antonio, Texas 78284-7811|
|University of Wisconsin Comprehensive Cancer Center||Madison, Wisconsin 53792|
|Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute||Boston, Massachusetts 02115|
|UCSF Comprehensive Cancer Center||San Francisco, California 94115|
|Hillman Cancer Center at University of Pittsburgh Cancer Institute||Pittsburgh, Pennsylvania 15236|
|Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas||Dallas, Texas 75390-9063|
|Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support||Bethesda, Maryland 20892-1182|