Phase I/II Study of OSI-774 (Erlotinib) and CCI-779 (Temsirolimus) in Patients With Recurrent Malignant Glioma
- Determine the maximum tolerated dose of temsirolimus when administered with erlotinib
in patients with recurrent malignant glioma. (Phase I)
- Determine the safety of this regimen in these patients. (Phase I)
- Determine the pharmacokinetics of this regimen in these patients. (Phase I)
- Determine the efficacy of this regimen, in terms of 6-month progression-free survival,
in these patients. (Phase II)
- Determine overall progression-free survival of patients treated with this regimen.
- Determine response in patients treated with this regimen. (Phase II)
- Correlate response to treatment with the molecular phenotype of the tumor in these
patients. (Phase II)
OUTLINE: This is a multicenter, phase I, dose-escalation study of temsirolimus followed by a
phase II study. Patients are stratified according to study phase (I vs II), histology at
study enrollment (glioblastoma multiforme or gliosarcoma vs anaplastic glioma), preoperative
candidacy (yes vs no), and presence of measurable or evaluable disease (yes vs no).
- Phase I: Patients receive oral erlotinib once daily on days 1-28 and temsirolimus IV
over 30 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence
of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of temsirolimus 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: Patients receive temsirolimus at the MTD and erlotinib as in phase I.
- Phase II (preoperative component): Patients who are surgical candidates may opt to
undergo surgical resection of the tumor. Beginning 5-7 days before surgery, these
patients receive oral erlotinib once daily until surgery. Patients also receive
temsirolimus IV over 30 minutes at the MTD and then undergo surgical resection of the
tumor 3-24 hours later. Beginning 2-4 weeks after surgery, patients receive
temsirolimus at the MTD and erlotinib as in phase I.
PROJECTED ACCRUAL: A total of 3-24 patients will be accrued for the phase I portion of the
study within 1-8 months. A total of 50 patients (32 patients with glioblastoma multiforme
and 18 with anaplastic glioma) will be accrued for the phase II portion of the study within
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose (Phase I)
Patrick Y. Wen, MD
Dana-Farber Cancer Institute
United States: Food and Drug Administration
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|
|Duke Comprehensive Cancer Center||Durham, North Carolina 27710|
|University of Texas Health Science Center at San Antonio||San Antonio, Texas 78284-7811|
|University of Wisconsin Paul P. Carbone Comprehensive Cancer Center||Madison, Wisconsin 53792-6164|
|Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute||Boston, Massachusetts 02115|
|Jonsson Comprehensive Cancer Center at UCLA||Los Angeles, California 90095-1781|
|UCSF Helen Diller Family Comprehensive Cancer Center||San Francisco, California 94115|
|M. D. Anderson Cancer Center at University of Texas||Houston, Texas 77030-4009|
|UPMC Cancer Centers||Pittsburgh, Pennsylvania 15232|
|Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office||Bethesda, Maryland 20892-1182|