Phase I/II Study of Two Different Schedules of Pemetrexed (ALIMTA) and Erlotinib (TARCEVA) in Advanced Solid Tumors, With Emphasis on Non-Small Cell Lung Cancer (NSCLC)
- Determine the safety and feasibility of combining pemetrexed disodium with erlotinib
hydrochloride in patients with advanced non-small lung cancer (NSCLC) or other solid
tumors. (Phase I)
- Determine the response rate in patients with NSCLC treated with pemetrexed disodium in
combination with erlotinib hydrochloride. (Phase II)
- Compare toxicity differences between different schedules of pemetrexed disodium and
erlotinib hydrochloride. (Phase I)
- Determine the maximum tolerated dose (MTD) of 2 different schedules of pemetrexed
disodium and erlotinib hydrochloride. (Phase I)
- Determine, preliminarily, the efficacy of the combination of pemetrexed disodium and
erlotinib hydrochloride in patients with advanced solid tumors. (Phase I)
- Assess the overall survival and progression-free survival. (Phase II)
- Determine the frequency and severity of toxicities associated with the administration
of pemetrexed disodium and erlotinib hydrochloride. (Phase II)
OUTLINE: This is a multicenter, phase I dose-escalation study followed by a phase II
- Phase I: Patients are assigned to 1 of 2 treatment groups in an alternating fashion.
Once accrual to the first dose level in group 1 is complete, group 2 will open for
accrual to its first dose level.
- Group 1: Patients receive oral erlotinib hydrochloride once on days 2, 9, and 16
and pemetrexed disodium IV over 10 minutes on day 1. Treatment repeats every 21
days for 6 courses in the absence of unacceptable toxicity or disease progression.
- Group 2: Patients receive oral erlotinib hydrochloride once daily on days 2-16 and
pemetrexed disodium IV over 10 minutes on day 1. Treatment repeats every 21 days
for 6 courses in the absence of unacceptable toxicity or disease progression.
In both groups, patients may continue to receive erlotinib hydrochloride alone after
completion of 6 courses of erlotinib hydrochloride in combination with pemetrexed disodium.
In both groups, cohorts of 3-6 patients receive escalating doses of erlotinib hydrochloride
and pemetrexed disodium 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
- Phase II: Patients receive pemetrexed disodium at the MTD and erlotinib hydrochloride
at the MTD as in group 1 or 2 (whichever is more favorable).
After completion of study treatment, patients are followed periodically.
PROJECTED ACCRUAL: A total of 92 patients will be accrued for this study.
Allocation: Non-Randomized, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
Safety and feasibility (Phase I)
David Gandara, MD
University of California, Davis
United States: Federal Government
|University of California Davis Cancer Center||Sacramento, California 95817|