A Phase I Study of GTI-2040 in Combination With Oxaliplatin and Capecitabine in Patients With Advanced Metastatic Solid Tumors
I. To establish the maximum tolerated (MTD) of a 21 day cycle of capecitabine given orally
twice daily for 14 days in combination with oxaliplatin given intravenously on day 1 and
GTI-2040 given as a continuous infusion over 14 days in patients with advanced metastatic
II. To describe the toxicities at each dose level studied.
I. To evaluate the pharmacokinetics of GTI-2040, capecitabine, and oxaliplatin when these
are given in combination.
II. To evaluate levels of ribonucleotide reductase -M2 subunit (RR-M2) mRNA levels using
TaqMan RT-PCR in peripheral blood mononuclear cells and in tumor samples (when available).
TRF support will be required and sought.
III. To quantitate changes in dCTP levels in peripheral blood mononuclear cells during
treatment as a surrogate marker of RR inhibition. TRF support will be required and sought.
OUTLINE: This is a multicenter, dose-escalation study of capecitabine.
Patients receive GTI-2040 IV continuously on days 1-14, oral capecitabine twice daily on
days 2-15, and oxaliplatin IV over 2 hours on day 2 of the first course. In all subsequent
courses, capecitabine is administered on days 1-14, oxaliplatin is administered on day 1,
and GTI-2040 is administered as in course 1. Courses repeat every 21 days in the absence of
disease progression and 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.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD of the combination of GTI-2040, oxaliplatin and capecitabine based on the incidence of dose-limiting toxicity (DLT) as assessed by CTCAE version 3.0
Adverse events will be summarized by grade, attribution, and organ system. Hematological and clinical chemistry laboratory results will be included in the adverse event summary.
Beckman Research Institute
United States: Food and Drug Administration
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