Trial Information

A Randomized Trial of Filgrastim-SD/01 vs. Filgrastim in Newly Diagnosed Children and Young Adults With Sarcoma Treated With Dose-Intensive Chemotherapy

Background:

- Filgrastim (granulocyte colony-stimulating factor), which is administered by daily
subcutaneous injection after cytotoxic chemotherapy, shortens the duration of
chemotherapy-induced neutropenia and lowers the risk of infection.

- In children treated with dose-intensive chemotherapy, Filgrastim reduces the duration
of severe neutropenia and, as a result, has become a standard component of the
treatment regimen.

- Filgrastim-SD/01 (AMGEN), which is produced by PEGylation of the amino-terminus of
Filgrastim, is a sustained duration form of granulocyte colony-stimulating factor.

- In phase I and phase II trials in adults, a single dose of Filgrastim-SD/01 appears to
be equivalent to daily dosing of Filgrastim in enhancing neutrophil recovery and has a
comparable adverse event profile.

- Dose-intensive vincristine/cyclophosphamide/doxorubicin (VDoxC) alternating with
ifosfamide/etoposide (IE) has become standard therapy for children and adolescents with
Ewing's sarcoma and other sarcomas treated at the POB/NCI and other cancer centers
within the US.

Objectives:

- Compare the tolerance, toxicity, and therapeutic effects of Filgrastim-SD/01 given as a
single injection after chemotherapy to daily subcutaneous Filgrastim in patients with
newly diagnosed sarcoma receiving multi-agent, dose intensive chemotherapy.

- The pharmacokinetics of Filgrastim-SD/01 will also be compared to the pharmacokinetics
of Filgrastim.

- This trial will also be a platform for performing biological studies of these tumors
study neutrophil function and CD34 mobilization, and for detailed cardiac studies.

Eligibility:

- Children and young adults (less than 25 years) with previously untreated high-risk
sarcomas (Ewing sarcoma, rhabdomyosarcoma, MPNST, and synovial sarcoma).

- No evidence of tumor infiltration of the bone marrow.

Design:

- Participants will be randomized (1:1) to receive a single dose of Filgrastim-SD/01 or
daily filgrastim as a SQ injection after each cycle of chemotherapy.

- Standard 5 drug dose-intensive chemotherapy with vincristine, doxorubicin,
cyclophosphamide alternating with ifosfamide and etoposide will be administered.

- Surgery or radiation for the primary tumor will occur after cycle 5.

- A total of 34 patients (17 patients per treatment arm) will be entered onto the trial.