A Phase I/II Study of Oblimersen Sodium (G3139, Genasense) in Combination With Oxaliplatin, 5FU and Leucovorin (FOLFOX4) Regimen in Advanced Colorectal Cancer
- Determine the maximum tolerated dose of oblimersen when administered with oxaliplatin,
fluorouracil, and leucovorin calcium in patients with advanced colorectal cancer.
- Determine the quantitative and qualitative toxic effects of this regimen in these
- Determine the antitumor activity of this regimen in these patients.
- Determine the plasma pharmacokinetics of oblimersen and oxaliplatin in patients treated
with this regimen.
- Determine relevant predictive biomarkers of response in patients treated with this
OUTLINE: This is an open-label, phase I, dose-escalation study of oblimersen followed by a
non-randomized, phase II study.
- Phase I: Patients receive oblimersen IV continuously on days 1-5 and 15-19; leucovorin
calcium IV over 2 hours and fluorouracil IV over 22 hours on days 6, 7, 20, and 21; and
oxaliplatin IV over 2 hours on days 6 and 20.
Cohorts of 3-6 patients receive escalating doses of oblimersen until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the highest dose at which no more than 1 of
6 patients experiences dose-limiting toxicity.
- Phase II: Up to 35 additional patients are treated as in phase I, with oblimersen at
In both phases, courses repeat every 28 days in the absence of disease progression or
Patients are followed at 30 days.
PROJECTED ACCRUAL: A total of 6-53 patients (6-18 patients for phase I and 12-35 patients
for phase II) will be accrued for this study.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Anthony W. Tolcher, MD
San Antonio Cancer Institute
United States: Food and Drug Administration
|San Antonio Cancer Institute||San Antonio, Texas 78229-3264|