A Phase I Trial Of G3139 (BCL-2 Antisense, NSC# 683428, IND# 58842) Combined With Cytotoxic Chemotherapy In Relapsed Childhood Solid Tumors
I. Determine the dose-limiting toxic effects and recommended phase II dose of oblimersen
when combined with cyclophosphamide, doxorubicin, and dexrazoxane in pediatric patients with
relapsed or refractory solid tumors.
II. Determine the pharmacokinetic behavior of this regimen in these patients. III.
Determine, preliminarily, the antitumor activity of oblimersen in these patients.
IV. Assess the biologic activity of oblimersen in mononuclear cells and tumor tissues, in
terms of bcl-2 and related protein expression, in these patients.
OUTLINE: This is a 2-part, multicenter, dose-escalation study.
Part A: Patients receive oblimersen IV continuously on days 1-7. Patients also receive
dexrazoxane IV followed by doxorubicin IV over 15 minutes followed by cyclophosphamide IV
over 1 hour on days 5 and 6. Filgrastim (G-CSF) is administered subcutaneously once daily
beginning on day 8 and continuing until blood counts recover. Treatment repeats every 21
days for up to 18 courses (1 year) in the absence of disease progression or unacceptable
toxicity. Patients with stable or responding disease whose shortening fraction falls below
28% by echocardiogram or whose total life-time cumulative anthracycline dose exceeds 750
mg/m^2 may receive additional courses of oblimersen and cyclophosphamide without doxorubicin
Cohorts of 3-6 patients receive escalating doses of oblimersen until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2
of 3 or 2 of 6 patients experience dose-limiting toxicity.
Part B: Patients receive oblimersen at the MTD determined in part A and escalating doses of
dexrazoxane, doxorubicin, and cyclophosphamide on the same treatment schedule as in part A.
Cohorts of 3-6 patients receive escalating doses of dexrazoxane, doxorubicin, and
cyclophosphamide until the maximum tolerated dose (MTD) is determined. The MTD is defined as
the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting
Patients are followed for survival.
PROJECTED ACCRUAL: A total of 12-15 patients will be accrued for this study within 1-2
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Dose-limiting toxic effects and recommended phase II dose, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0
Up to day 21
Children's Oncology Group
United States: Food and Drug Administration
|Children's Oncology Group||Arcadia, California 91006-3776|