Phase I Study of Imatinib, Gemcitabine and Capecitabine in Patients With Solid Tumors
- Determine the maximum tolerated dose of gemcitabine hydrochloride and capecitabine when
combined with imatinib mesylate in patients with advanced solid tumors.
- Determine the toxicity of this regimen in these patients.
- Explore the antitumor activity of this regimen in these patients.
OUTLINE: This is a dose-escalation study of gemcitabine and capecitabine.
Patients receive oral imatinib mesylate once daily on days 1-5 and 8-12, gemcitabine
hydrochloride IV on days 3 and 10, and oral capecitabine twice daily on days 1-14. Treatment
repeats every 21 days for at least 2 courses in the absence of progressive disease or
Cohorts of 3-6 patients receive escalating doses of gemcitabine hydrochloride and
capecitabine 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.
Existing paraffin-embedded tissue blocks from patients diagnosed with melanoma or renal cell
carcinoma will be assessed for c-kit mutations by polymerase chain reaction and direct
sequencing of both juxtamembrane domains (exons 9 and 11) and tyrosine kinase domain (exon
13 and 17). (Begins 12-11-2008)
PROJECTED ACCRUAL: Closed to patient accrual 12/11/2008.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of gemcitabine hydrochloride and capecitabine when combined with imatinib mesylate
Cohorts of 3 starting at dose level 0. The imatinib dose is fixed. The dose of capecitabine is initially fixed and the dose of gemcitabine is increased 1 dose level. For the subsequent cohort, the dose of gemcitabine will be fixed and the dose of capecitabine advanced to the next dose level. 3 patients will be treated on the initial schedule. If no dose-limiting toxicities related to drug are observed and no patients require dose mods by the end of cycle 2, then 3 patients will be treated on the next schedule.
By the end of cycle 2
Ralph Hauke, MD
University of Nebraska
United States: Federal Government
|UNMC Eppley Cancer Center at the University of Nebraska Medical Center||Omaha, Nebraska 68198-7680|