Phase I Study of Decitabine (NSC #127716, IND #50733) in Combination With Doxorubicin and Cyclophosphamide in the Treatment of Relapsed or Refractory Solid Tumors

Inclusion Criteria:

- Histologically confirmed diagnosis of either of the following:

- Solid tumor (part A)

- No lymphoma

- Neuroblastoma (part B)

- Original diagnosis may be based on elevated urine vanillylmandelic acid
(VMA) and homovanillic acid (HVA) and bone marrow examination

- Accessible disease by bone marrow aspirate or tumor biopsy

- No laparotomy, thoracotomy, endoscopy, or craniotomy for biopsy

- No known curative therapy OR therapy proven to prolong survival with an acceptable
quality of life available

- No known brain or spinal cord metastases

- No CNS tumors

- Performance status - Karnofsky 50-100% (patients 11 to 21 years of age)

- Performance status - Lansky 50-100% (patients ≤ 10 years of age)

- Parts A and B without bone marrow infiltration:

- Absolute neutrophil count ≥ 1,000/mm^3

- Platelet count ≥ 100,000/mm^3 (transfusion independent)

- Part B with bone marrow infiltration (i.e., tumor metastatic to bone marrow with
granulocytopenia, anemia, and/or thrombocytopenia):

- Absolute neutrophil count ≥ 750/mm^3

- Platelet count ≥ 50,000/mm^3 (transfusion independent)

- Hemoglobin ≥ 8.0 g/dL (transfusion allowed)

- No sickle cell anemia

- Bilirubin ≤ 1.5 mg/dL

- ALT ≤ 5 times upper limit of normal

- No significant hepatic dysfunction that would compromise the tolerability of
decitabine or interfere with study procedures or results

- Creatinine based on age as follows:

- ≤ 0.8 mg/dL (5 years of age and under)

- ≤ 1.0 mg/dL (6 to 10 years of age)

- ≤ 1.2 mg/dL (11 to 15 years of age)

- ≤ 1.5 mg/dL (16 to 21 years of age)

- Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min

- No significant renal dysfunction that would compromise the tolerability of decitabine
or interfere with study procedures or results

- Shortening fraction ≥ 28% by echocardiogram

- Ejection fraction of ≥ 45% by MUGA

- No significant pulmonary dysfunction that would compromise the tolerability of
decitabine or interfere with study procedures or results

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No prior allergic reaction attributed to compounds of similar chemical or biological
composition to agents used in this study

- No uncontrolled serious infection

- No significant end-organ dysfunction that would compromise the tolerability of
decitabine or interfere with study procedures or results

- Recovered from prior immunotherapy

- At least 7 days since prior biologic therapy

- More than 1 week since prior growth factor therapy (2 weeks for pegfilgrastim)

- More than 2 weeks since prior epoetin alfa

- At least 6 months since prior autologous stem cell transplantation

- At least 6 months since prior allogeneic bone marrow transplantation

- Patients must have full organ recovery and no evidence of graft-versus-host
disease

- No concurrent immunomodulating agents

- No concurrent immunotherapy

- No concurrent biologic therapy

- No concurrent epoetin alfa

- Recovered from prior chemotherapy

- More than 2 weeks since prior myelosuppressive chemotherapy (6 weeks for
nitrosoureas)

- Prior total lifetime cumulative anthracycline dose ≤ 450 mg/m^2 of doxorubicin or
equivalent

- No other concurrent chemotherapy

- No concurrent hydroxyurea

- Recovered from prior radiotherapy

- More than 2 weeks since prior local palliative small port radiotherapy

- More than 6 months since prior substantial bone marrow irradiation (e.g.,
cranio-spinal irradiation, total body irradiation, or hemi-pelvic irradiation)

- No concurrent radiotherapy

- No other concurrent anticancer therapy

- No other concurrent investigational agents

- Concurrent oral iron supplementation for patients with a known iron deficiency or a
microcytic hypochromic anemia allowed