Oblimersen Plus Combination Chemotherapy and Dexrazoxane in Treating Children and Adolescents With Relapsed or Refractory Solid Tumors
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
Unspecified Childhood Solid Tumor, Protocol Specific
Biological: oblimersen sodium
Drug: dexrazoxane hydrochloride
Drug: doxorubicin hydrochloride
Other: laboratory biomarker analysis
Other: pharmacological study
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Trial Of G3139 (BCL-2 Antisense, NSC# 683428, IND# 58842) Combined With Cytotoxic Chemotherapy In Relapsed Childhood Solid Tumors|
- Dose-limiting toxic effects and recommended phase II dose, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 [ Time Frame: Up to day 21 ] [ Designated as safety issue: No ]
- Change in pharmacokinetic behavior of this regimen [ Time Frame: Days 1 (pre-infusion), 5, 6, and 8 (end of infusion) ] [ Designated as safety issue: No ]
- Antitumor activity [ Time Frame: Up to day 21 ] [ Designated as safety issue: No ]
- Biologic activity of oblimersen in mononuclear cells and tumor tissues, in terms of B-cell lymphoma 2 (bcl-2) and related protein expression [ Time Frame: Up to day 21 ] [ Designated as safety issue: No ]
|Study Start Date:||November 2002|
|Primary Completion Date:||October 2005 (Final data collection date for primary outcome measure)|
Experimental: Treatment (Oblimersen sodium, cytotoxic chemotherapy)
See detailed description.
Biological: oblimersen sodium
Other Names:Drug: dexrazoxane hydrochloride
Other Names:Drug: doxorubicin hydrochloride
Other Names:Drug: cyclophosphamide
Other Names:Biological: filgrastim
Other Names:Other: laboratory biomarker analysis
Correlative studiesOther: pharmacological study
Other Name: pharmacological studies
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00039481
|United States, California|
|Children's Oncology Group|
|Arcadia, California, United States, 91006-3776|
|Principal Investigator:||Susan Rheingold||Children's Oncology Group|