NCT00039481

Oblimersen Plus Combination Chemotherapy and Dexrazoxane in Treating Children and Adolescents With Relapsed or Refractory Solid Tumors

A Phase I Trial Of G3139 (BCL-2 Antisense, NSC# 683428, IND# 58842) Combined With Cytotoxic Chemotherapy In Relapsed Childhood Solid Tumors

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 15 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 1 Year – 21 Years
• Healthy volunteers: Not accepted

Summary

Phase I trial to study the effectiveness of oblimersen plus combination chemotherapy and dexrazoxane in treating children and adolescents who have relapsed or refractory solid tumors. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Oblimersen may increase the effectiveness of doxorubicin and cyclophosphamide by making the tumor cells more sensitive to the drug. Chemoprotective drugs such as dexrazoxane may protect normal cells from the side effects of chemotherapy

Detailed description

OBJECTIVES: 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 and dexrazoxane. 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 toxicity. Patients are followed for survival. PROJECTED ACCRUAL: A total of 12-15 patients will be accrued for this study within 1-2 years.

Conditions

• Cardiac Toxicity
• Unspecified Childhood Solid Tumor, Protocol Specific

Interventions

Type	Name	Description
BIOLOGICAL	oblimersen sodium	Given IV
DRUG	dexrazoxane hydrochloride	Given IV
DRUG	doxorubicin hydrochloride	Given IV
DRUG	cyclophosphamide	Given IV
BIOLOGICAL	filgrastim	Given SC
OTHER	laboratory biomarker analysis	Correlative studies
OTHER	pharmacological study	Correlative studies

Timeline

• Start date: 2002-11-01
• Primary completion: 2005-10-01
• First posted: 2003-01-27
• Last updated: 2013-01-17

Locations

1 site across 1 country: United States