A Phase I Study of Intravenous (IV) Calcitriol in Combination With ZD1839 (IRESSA®) in Refractory Solid Tumors
- Determine the maximum tolerated dose (MTD), toxic effects, and tolerability of
calcitriol alone and in combination with gefitinib with or without dexamethasone in
patients with advanced solid tumors.
- Determine the pharmacokinetics and pharmacodynamics of these regimens in these
- Determine any tumor responses in patients treated with these regimens.
OUTLINE: This is a dose-escalation study of calcitriol.
- Stage 1: Patients receive calcitriol IV over 1 hour on days 1, 15, and 22 and oral
gefitinib once daily on days 8-28 during course 1. For all subsequent courses, patients
receive calcitriol IV over 1 hour on days 1, 8, 15, and 22 and oral gefitinib once
daily on days 1-28. Courses repeat every 28 days in the absence of disease progression
or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of calcitriol with a fixed dose of
gefitinib 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.
- Stage 2: Patients receive calcitriol (beginning at 1 dose level below the MTD
determined in stage 1) and gefitinib as in stage 1. Patients also receive oral
dexamethasone once on the day before and twice on the day of each dose of calcitriol.
Cohorts 3-6 patients receive escalating doses of calcitriol with fixed doses of gefitinib
and dexamethasone until the 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.
PROJECTED ACCRUAL: A total of 21-36 patients will be accrued for this study within 1 year.
Intervention Model: Single Group Assignment, Primary Purpose: Treatment
Maximum tolerated dose
Marwan Fakih, MD
Roswell Park Cancer Institute
United States: Food and Drug Administration
|Roswell Park Cancer Institute||Buffalo, New York 14263|