A Phase I Trial of Epirubicin, Carboplatin and Capecitabine in Adult Cancer Patients
- Determine the recommended phase II dose of capecitabine when given together with
epirubicin hydrochloride and carboplatin in patients with progressive, unresectable, or
- Determine the toxicities of this regimen in these patients.
- Correlate end-of-infusion levels of epirubicin hydrochloride and its metabolites with
epirubicin hydrochloride dose and clinical toxicity in these patients.
- Correlate the pharmacokinetics of capecitabine with clinical toxicity in these
- Determine the possible correlation between polymorphisms in the promoter region of the
thymidylate synthase gene with clinical toxicity in these patients.
- Document antitumor activity of this regimen in these patients.
OUTLINE: This is a dose-escalation study of capecitabine.
Patients receive epirubicin hydrochloride IV over 2 hours and carboplatin IV over 30 minutes
on day 1 and oral capecitabine twice daily on days 2-5, 8-12, and 15-19. Treatment repeats
every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of 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.
Peripheral blood is collected for pharmacokinetic and pharmacogenetic studies before
beginning study treatment and periodically during study. Samples for the pharmacogenetic
studies are analyzed for correlation between polymorphisms in the promoter region of the
thymidylate synthase gene and clinical toxicity. Patients also undergo bone marrow aspirate
before beginning study treatment for molecular profiling studies.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Recommended phase II dose of capecitabine
Every 28-days until progression.
Jean L. Grem, MD
University of Nebraska
United States: Institutional Review Board
|UNMC Eppley Cancer Center at the University of Nebraska Medical Center||Omaha, Nebraska 68198-7680|