Decitabine, Doxorubicin, and Cyclophosphamide in Treating Children With Relapsed or Refractory Solid Tumors or Neuroblastoma
Condition: Recurrent Neuroblastoma; Unspecified Childhood Solid Tumor, Protocol Specific
MeSH terms: Neuroblastoma
Study type: Interventional
Phase: Phase 1

Summary: 
      This phase I trial is studying the side effects and best dose of decitabine when given
      together with doxorubicin and cyclophosphamide in treating children with relapsed or
      refractory solid tumors or neuroblastoma. Drugs used in chemotherapy, such as decitabine,
      doxorubicin, and cyclophosphamide, work in different ways to stop tumor cells from dividing
      so they stop growing or die. Combining more than one drug may kill more tumor cells.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. Determine the maximum tolerated dose of decitabine in combination with doxorubicin and
      cyclophosphamide in children with relapsed or refractory solid tumors or neuroblastoma.

      II. Determine the toxic effects of this regimen in these patients. III. Determine whether
      decitabine induces tumor caspase-8 demethylation and expression in these patients.

      SECONDARY OBJECTIVES:

      I. Determine the pharmacokinetics of low-dose decitabine in these patients. II. Determine the
      biological and clinical response in patients treated with this regimen.

      III. Compare patterns of peripheral blood gene expression, using gene expression profiling,
      in patients before and after treatment with decitabine.

      OUTLINE: This is a multicenter, dose-escalation study of decitabine.

      PART A (solid tumor patients): Patients receive decitabine IV over 1 hour on days 0-6 and
      doxorubicin IV over 15 minutes and cyclophosphamide IV over 1 hour on day 7. Patients then
      receive filgrastim (G-CSF) subcutaneously (SC) beginning on day 8 and continuing until blood
      counts recover OR pegfilgrastim SC once on day 8 or 9*. Treatment repeats every 28 days for
      up to 12 courses in the absence of disease progression or unacceptable toxicity.

      Cohorts of 3-6 patients receive escalating doses of decitabine until the maximum tolerated
      dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
      of 6 patients experience dose-limiting toxicity.

      NOTE: *For patients > 45 kg

      PART B (neuroblastoma patients): Once the MTD is determined for part A, patients are treated
      as in part A at the MTD.

      Patients are followed at 30 days.
    

Intervention name(s): decitabine; doxorubicin hydrochloride; cyclophosphamide; filgrastim; pegfilgrastim; laboratory biomarker analysis; pharmacological study
Intervention type(s): Drug; Drug; Drug; Biological; Biological; Other; Other
Intervention description(s): Given IV; Given IV; Given IV; Given SC; Given SC; Correlative studies; Correlative studies
Other intervention name(s): 5-aza-dCyd; 5AZA; DAC; ADM; ADR; Adria; Adriamycin PFS; Adriamycin RDF; CPM; CTX; Cytoxan; Endoxan; Endoxana; G-CSF; Neupogen; Filgrastim SD-01; GCSF-SD01; Neulasta; SD-01 sustained duration G-CSF; pharmacological studies
Intervention MeSH terms: Cyclophosphamide; Doxorubicin; Liposomal doxorubicin; Decitabine; Azacitidine; Lenograstim
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment