A Phase I/II Trial of ZD1839 (Iressa®) and Rapamycin (Rapamune) in Patients With Advanced Non Small Cell Lung Cancer
- Determine the maximum tolerated dose of sirolimus when combined with gefitinib in
patients with recurrent or refractory stage IIIB or IV non-small cell lung cancer.
- Determine the overall response rate (complete response [CR] and partial response [PR])
in patients treated with this regimen.
- Determine the disease control rate (CR, PR, and stable disease) in patients treated
with this regimen.
- Determine the time to progression and overall survival of patients treated with this
- Determine the quality of life of patients treated with this regimen.
OUTLINE: This is an open-label, phase I, dose-escalation study of sirolimus followed by a
phase II study.
- Phase I: Patients receive oral gefitinib once daily and oral sirolimus once daily on
days 1-28. Courses repeat every 28 days in the absence of unacceptable toxicity or
Cohorts of 3-6 patients receive escalating doses of sirolimus 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 gefitinib and sirolimus as in phase I at the MTD. Quality of
life is assessed at baseline, day 1 of each course, and then at 1 month
Patients are followed every 9 weeks. Patients withdrawn from study treatment without
evidence of disease progression are followed every 6 weeks until disease progression.
PROJECTED ACCRUAL: A total of 25 patients (11 for phase I and 14 for phase II) will be
accrued for this study within 8.3 months.
Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose (Phase I)
Fairooz F. Kabbinavar, MD
Jonsson Comprehensive Cancer Center
United States: Food and Drug Administration