Phase I Study of Decitabine (NSC #127716, IND #50733) in Combination With Doxorubicin and Cyclophosphamide in the Treatment of Relapsed or Refractory Solid Tumors
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.
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.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD of decitabine, based on incidence of DLT graded according to NCI CTCAE version 3.0 (Part A)
Up to 28 days
Children's Oncology Group
United States: Food and Drug Administration
|Children's Oncology Group||Arcadia, California 91006-3776|