Erlotinib and Temsirolimus in Treating Patients With Recurrent Malignant Glioma
RATIONALE: Erlotinib and temsirolimus and may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase I/II trial is studying the side effects and best dose of temsirolimus when given together with erlotinib and to see how well they work in treating patients with recurrent malignant glioma.
Brain and Central Nervous System Tumors
Drug: erlotinib hydrochloride
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Study of OSI-774 (Erlotinib) and CCI-779 (Temsirolimus) in Patients With Recurrent Malignant Glioma|
- Maximum tolerated dose (Phase I) [ Designated as safety issue: Yes ]
- Safety (Phase I) [ Designated as safety issue: Yes ]
- Pharmacokinetics (Phase I) [ Designated as safety issue: No ]
- Efficacy (Phase I) [ Designated as safety issue: No ]
- Progression-free survival at 6 months (Phase II) [ Designated as safety issue: No ]
- Response rate (Phase II) [ Designated as safety issue: No ]
|Study Start Date:||April 2005|
|Primary Completion Date:||April 2010 (Final data collection date for primary outcome measure)|
- 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. (Phase II)
- 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 8-12 months.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00112736
|United States, California|
|Jonsson Comprehensive Cancer Center at UCLA|
|Los Angeles, California, United States, 90095-1781|
|UCSF Helen Diller Family Comprehensive Cancer Center|
|San Francisco, California, United States, 94115|
|United States, Maryland|
|Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office|
|Bethesda, Maryland, United States, 20892-1182|
|United States, Massachusetts|
|Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|United States, New York|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10021|
|United States, North Carolina|
|Duke Comprehensive Cancer Center|
|Durham, North Carolina, United States, 27710|
|United States, Pennsylvania|
|UPMC Cancer Centers|
|Pittsburgh, Pennsylvania, United States, 15232|
|United States, Texas|
|M. D. Anderson Cancer Center at University of Texas|
|Houston, Texas, United States, 77030-4009|
|University of Texas Health Science Center at San Antonio|
|San Antonio, Texas, United States, 78284-6220|
|United States, Wisconsin|
|University of Wisconsin Paul P. Carbone Comprehensive Cancer Center|
|Madison, Wisconsin, United States, 53792-6164|
|Study Chair:||Patrick Y. Wen, MD||Dana-Farber Cancer Institute|