Trial Information

Phase I Study of Amifostine (Ethyol) as a Cytoprotector of Gemcitabine/Cisplatin Combination

OBJECTIVES: I. Evaluate the ability of amifostine to facilitate increased dose escalation of
gemcitabine and cisplatin. II. Compare the dose limiting toxicities of gemcitabine and
cisplatin administered with and without amifostine in these patients. III. Determine the
maximum tolerated dose of gemcitabine and cisplatin administered with amifostine in these
patients. IV. Determine whether synergy is produced by administering gemcitabine and
cisplatin on the same day.

OUTLINE: This is a two stage study. The first stage is a randomized study, and the second
stage is a dose escalation study. In the first stage of the study, patients receive either
intravenous gemcitabine/amifostine/cisplation (GAP) or gemcitabine/cisplatin (GP) in the
first cycle. Patients are administered the other arm in the second cycle. In the second
stage of the study (dose escalation), the initial dose of GP or GAP is given on days 1 and 8
every 28 days. Dose escalation is carried out in cohorts of 3 patients per dose level. If 1
of 3 patients experiences dose limiting toxicity (DLT), then 3 more patients are accrued at
the same dose level. The maximum tolerated dose (MTD) is defined as the lowest dose at which
2 of 6 or 2 of 3 patients experience DLT. Patients experiencing grade 3 or 4 toxicity or
tumor progression are removed from the study. Patients will be reassessed every 12 weeks.

PROJECTED ACCRUAL: A total of 32 patients will be accrued over 12-24 months in the first
stage of this study, and 9-12 patients will be accrued for the second stage..