A Pilot Trial of Daily Oral ZD1839 (Iressa) With Standard Doses of Carboplatin and Paclitaxel in Patients With Advanced Non-Small Cell Lung Cancer
OBJECTIVES: I. Determine the maximum tolerated dose of ZD 1839 given intermittently or
continuously and concurrently with standard doses of carboplatin and paclitaxel in patients
with advanced non-small cell lung cancer. II. Determine the safety of ZD 1839 in these
regimens in these patients. III. Determine whether the exposure of either free carboplatin
or paclitaxel in an established treatment regimen is significantly altered by the addition
of oral ZD 1839 in this patient population. IV. Determine the exposure of ZD 1839 before and
after standard doses of carboplatin and paclitaxel to assess whether ZD 1839 steady state is
significantly altered by coadministration of chemotherapy.
OUTLINE: This is an open label, 2 part, multicenter study. Part 1 is a randomized, dose
escalation, 2 period, 2 sequence, crossover design. Part 2 is a nonrandomized, single dose
evaluation design. Part 1: Patients are randomized to receive ZD 1839 beginning 1 week
before either the first (arm I) or second (arm II) course of carboplatin and paclitaxel. Arm
I: Patients receive oral ZD 1839 daily on days 1-14. On day 1 only, ZD 1839 is given twice
at 12 hour intervals. Patients receive paclitaxel IV over 3 hours followed by carboplatin IV
over 30 minutes on days 8 and 36. Subsequent courses consist of ZD 1839 for 14 days and
paclitaxel and carboplatin every 28 days. Arm II: Patients receive paclitaxel and
carboplatin as in arm I on days 1 and 29. Patients receive oral ZD 1839 daily on days 22-35.
On day 22 only, ZD 1839 is given twice at 12 hour intervals. Subsequent courses are
administered as in arm I. Part 2: Patients receive oral ZD 1839 daily on days 1-56. On day 1
only, ZD 1839 is given twice at 12 hour intervals. Patients receive paclitaxel and
carboplatin as in part 1 on days 8 and 36. Subsequent courses consist of ZD 1839
continuously and paclitaxel and carboplatin every 28 days. Treatment continues in both parts
for a maximum of 6 months in the absence of unacceptable toxicity or disease progression. In
both parts 1 and 2, cohorts of 6-12 patients receive escalating doses of ZD 1839 until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at
which 4 of 6 or 4 of 12 patients experience dose limiting toxicities.
PROJECTED ACCRUAL: A maximum of 48 patients will be accrued for this study.
Primary Purpose: Treatment
Vincent A. Miller, MD
Memorial Sloan-Kettering Cancer Center
United States: Federal Government
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