Oblimersen Plus Combination Chemotherapy and Dexrazoxane in Treating Children and Adolescents With Relapsed or Refractory Solid Tumors
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|ClinicalTrials.gov Identifier: NCT00039481|
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : January 17, 2013
|Condition or disease||Intervention/treatment||Phase|
|Cardiac Toxicity Unspecified Childhood Solid Tumor, Protocol Specific||Biological: oblimersen sodium Drug: dexrazoxane hydrochloride Drug: doxorubicin hydrochloride Drug: cyclophosphamide Biological: filgrastim Other: laboratory biomarker analysis Other: pharmacological study||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||15 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Trial Of G3139 (BCL-2 Antisense, NSC# 683428, IND# 58842) Combined With Cytotoxic Chemotherapy In Relapsed Childhood Solid Tumors|
|Study Start Date :||November 2002|
|Actual Primary Completion Date :||October 2005|
Experimental: Treatment (Oblimersen sodium, cytotoxic chemotherapy)
See detailed description.
Biological: oblimersen sodium
Drug: dexrazoxane hydrochloride
Drug: doxorubicin hydrochloride
Other: laboratory biomarker analysis
Other: pharmacological study
Other Name: pharmacological studies
- 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 ]
- Change in pharmacokinetic behavior of this regimen [ Time Frame: Days 1 (pre-infusion), 5, 6, and 8 (end of infusion) ]
- Antitumor activity [ Time Frame: Up to day 21 ]
- 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 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00039481
|United States, California|
|Children's Oncology Group|
|Arcadia, California, United States, 91006-3776|
|Principal Investigator:||Susan Rheingold||Children's Oncology Group|