Decitabine, Doxorubicin, and Cyclophosphamide in Treating Children With Relapsed or Refractory Solid Tumors or Neuroblastoma

NCT00075634 | Completed Phase 1

• 5 other identifiers: NCI-2012-01807CDR0000347393COG-ADVL0215ADVL0215U01CA097452
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Recurrent Neuroblastoma; Unspecified Childhood Solid Tumor, Protocol Specific

Outcome Measures

Primary Outcomes (2)

• MTD of decitabine, based on incidence of DLT graded according to NCI CTCAE version 3.0 (Part A)

  Up to 28 days

• Caspase-8 expression in bone marrow or tumor biopsy samples (Part B)

  Up to 28 days

Secondary Outcomes (2)

• Objective response rate

  Up to 56 days

• Percent of apoptotic cells as assessed by a TUNEL assay

  Up to 1 year

Study Arms (1)

Arm I

EXPERIMENTAL

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. PART B (neuroblastoma patients): Once the MTD is determined for part A, patients are treated as in part A at the MTD.

Drug: decitabine; Drug: doxorubicin hydrochloride; Drug: cyclophosphamide; Biological: filgrastim; Biological: pegfilgrastim; Other: laboratory biomarker analysis; Other: pharmacological study

Interventions

decitabine DRUG

Given IV

Also known as: 5-aza-dCyd, 5AZA, DAC

Arm I

doxorubicin hydrochloride DRUG

Given IV

Also known as: ADM, ADR, Adria, Adriamycin PFS, Adriamycin RDF

Arm I

cyclophosphamide DRUG

Given IV

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana

Arm I

filgrastim BIOLOGICAL

Given SC

Also known as: G-CSF, Neupogen

Arm I

pegfilgrastim BIOLOGICAL

Given SC

Also known as: Filgrastim SD-01, GCSF-SD01, Neulasta, SD-01 sustained duration G-CSF

Arm I

laboratory biomarker analysis OTHER

Correlative studies

Arm I

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Arm I

Eligibility Criteria

• Age: 1 Year - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Children's Oncology Group

Arcadia, California, 91006-3776, United States

Location

MeSH Terms

Conditions

Neuroblastoma

Interventions

Decitabine; Doxorubicin; Cyclophosphamide; Filgrastim; Granulocyte Colony-Stimulating Factor; pegfilgrastim

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Rani George

  COG Phase I Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2004
• First Posted: January 12, 2004
• Study Start: December 1, 2003
• Primary Completion: September 1, 2007
• Last Updated: September 30, 2013

Record last verified: 2013-09

Locations

US (1)