A Phase I/II Trial to Assess the Tolerability of RAD 001 With Gefitinib in Patients With Glioblastoma Multiforme and Prostate Cancer and Efficacy in Patients With Castrate Metastatic Prostate Cancer
- Determine the maximum tolerated dose of everolimus when given in combination with
gefitinib in patients with progressive glioblastoma multiforme or (progressive castrate
metastatic prostate cancer -closed to accrual as of 10/19/2006). (Phase I)
- Determine the safety and efficacy of this regimen in patients with progressive
glioblastoma multiforme or (progressive castrate metastatic prostate cancer - closed to
accrual as of 10/19/2006). (Phase II)
- Determine whether a pharmacokinetic interaction exists between everolimus and gefitinib
in patients treated with this regimen.
- Determine the association between clinical outcomes and markers that may predict
sensitivity of a tumor in patients treated with this regimen.
- Determine the pharmacodynamic effects of this regimen on post-therapy tumor specimens
and peripheral blood mononuclear cells from these patients.
OUTLINE: This is a phase I, open-label, non-randomized, dose-escalation study of everolimus
followed by a phase II study.
- Phase I: Patients receive oral everolimus on day 1 and oral gefitinib once daily on
days 8-21. Beginning on day 22, patients receive oral everolimus once weekly and oral
gefitinib once daily. Treatment with the combination continues in the absence of
disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of everolimus 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.
- Phase II (prostate cancer patients only) (closed to accrual as of 10/19/2006): Patients
receive oral everolimus (at the MTD determined in phase I) once weekly and oral
gefitinib once daily. Treatment continues in the absence of disease progression or
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Safe and tolerable dose of everolimus (Phase I)
Howard I. Scher, MD
Memorial Sloan-Kettering Cancer Center
United States: Food and Drug Administration
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|