A Phase I/II, Pharmacokinetic, and Biologic Correlative Study of G3139, NSC # 683428 (Phosphorothioate Antisense Oligonucleotide Directed to Bcl-2) and Irinotecan in Patients With Metastatic Colorectal Cancer
OBJECTIVES: I. Determine the dose-limiting toxic effects and maximum tolerated dose of
augmerosen (G3139) administered in combination with irinotecan in patients with unresectable
metastatic or recurrent colorectal cancer. II. Determine the quantitative and qualitative
toxicity of this drug combination in this patient population. III. Assess the plasma
pharmacokinetics of this combination in these patients. IV. Document the antitumor activity
of this drug combination in these patients in a phase II study. V. Determine the relevant
biologic endpoints of treatment in tumor biopsies prior to and after therapy with G3139 at
two dose levels and assess the pharmacokinetic and pharmacodynamic correlations.
OUTLINE: This is a dose-escalation, multicenter study. Patients receive augmerosen (G3139)
IV continuously on days 1-7 and irinotecan IV over 90 minutes on day 6. Treatment continues
every 21 days in the absence of unacceptable toxicity or disease progression. Cohorts of 3-6
patients receive escalating doses of G3139 and irinotecan until the maximum tolerated dose
(MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients
experience dose-limiting toxicity. Once the MTD is determined, additional patients are
accrued to receive treatment with G3139 and irinotecan at the recommended phase II dose.
Patients are followed every 30 days until toxicity resolves.
PROJECTED ACCRUAL: A maximum of 18 patients will be accrued for the phase I portion of this
study. A maximum of 55 patients will be accrued for the phase II portion of this study.
Primary Purpose: Treatment
Anthony W. Tolcher, MD
San Antonio Cancer Institute
United States: Federal Food and Drug Administration
|Ireland Cancer Center||Cleveland, Ohio 44106-5065|
|Brooke Army Medical Center||Fort Sam Houston, Texas 78234-6200|
|San Antonio Cancer Institute||San Antonio, Texas 78229-3264|