Oblimersen Plus Combination Chemotherapy and Dexrazoxane in Treating Children and Adolescents With Relapsed or Refractory Solid Tumors
Condition: Cardiac Toxicity; Unspecified Childhood Solid Tumor, Protocol Specific
MeSH terms: Cardiotoxicity
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): oblimersen sodium; dexrazoxane hydrochloride; doxorubicin hydrochloride; cyclophosphamide; filgrastim; laboratory biomarker analysis; pharmacological study
Intervention type(s): Biological; Drug; Drug; Drug; Biological; Other; Other
Intervention description(s): Given IV; Given IV; Given IV; Given IV; Given SC; Correlative studies; Correlative studies
Other intervention name(s): augmerosen; G3139; G3139 bcl-2 antisense oligodeoxynucleotide; Genasense; Cardioxane; Savene; Totect; Zinecard; ADM; ADR; Adria; Adriamycin PFS; Adriamycin RDF; CPM; CTX; Cytoxan; Endoxan; Endoxana; G-CSF; Neupogen; pharmacological studies
Intervention MeSH terms: Cyclophosphamide; Doxorubicin; Liposomal doxorubicin; Dexrazoxane; Razoxane; Oblimersen
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment