A Phase I/II Study of Taxotere, Oxaliplatin, and 5- Fluorouracil
- To establish the maximum tolerated dose of docetaxel when administered with oxaliplatin
and fluorouracil in patients with metastatic or unresectable solid tumors. (Phase I)
- To determine the response rate in patients with metastatic or unresectable
adenocarcinoma of the stomach or gastroesophageal junction treated with this regimen.
- To determine the dose limiting toxicity of this regimen in these patients.
- To evaluate the frequency of CYP3A4, CYP3A5, and MDR polymorphisms and their impact on
toxicity of docetaxel.
- To evaluate the frequency of XRCC1 and ERCC2 polymorphisms and their impact on the
toxicity of oxaliplatin.
- To evaluate the frequency of DPD and TSER polymorphisms and their impact on the
toxicity of fluorouracil.
- To characterize the toxicity profile of this regimen in these patients.
OUTLINE: This is a dose-escalation study of docetaxel.
Patients receive docetaxel IV over 1 hour and oxaliplatin IV over 2 hours on day 1 and
fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment repeats every 14 days
for at least 2 courses in the absence of disease progression, symptomatic tumor progression,
or unacceptable toxicity.
Patients undergo blood sample collection periodically for pharmacokinetic and
pharmacogenomic correlative studies. Plasma concentrations of docetaxel are analyzed by
reverse-phase high performance liquid chromatography and tandem mass spectrometry.
Polymorphisms in CYP3A4/5, MDR, and other genes are analyzed by PCR.
After completion of study therapy, patients are followed every 3 months.
PROJECTED ACCRUAL: A total of 73 patients (30 for phase I and 43 for phase II) will be
accrued for this study.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of docetaxel when given in combination with oxaliplatin and fluorouracil (Phase I)
After completion of 1 cycle of therapy (1 cycle = 14 days)
Mary Mulcahy, MD
Robert H. Lurie Cancer Center
United States: Federal Government
|Robert H. Lurie Comprehensive Cancer Center at Northwestern University||Chicago, Illinois 60611|