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Ewing's SarcomaPhase 1NCT00004853

Comparison of Filgrastim and Filgrastim SD/01in Boosting White Cell Counts After Intensive Chemotherapy

A Phase 1 study testing Filgrastim and Filgrastim-SD/01 in people with Ewing's Sarcoma and Rhabdomyosarcoma, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages Up to 25 years
Conditions the study is for
Ewing's Sarcoma, Rhabdomyosarcoma, MPNST
What is being tested?
Filgrastim and Filgrastim-SD/01
Could I receive a placebo?
No, everyone receives an active treatment
How many people
34 participants
Where
1 siteUnited States
Study dates
3 Mar 2000to 20 May 2009
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 25 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Newly diagnosed histologically proven:
  • Ewing's sarcoma family of tumors, including peripheral neuroectodermal tumors;
  • Alveolar rhabdomyosarcoma;
  • Stage 3 or 4 embryonal rhabdomyosarcoma;
  • Malignant peripheral nerve sheath tumor that is unresectable, incompletely resected with bulk residual disease or metastatic;
  • Synovial cell sarcoma that is unresectable, incompletely resected with bulk residual disease, or metastatic.
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  • Age equal to or less than 25 years at the time of diagnosis.
  • Normal cardiac function (ejection fraction by MUGA or ECHO that is within the institutional normal range).
  • Normal serum creatinine for age or creatinine clearance greater than 60 ml/min/1.73m(2).
  • Normal liver function (SGPT less than 5 times the upper limit of normal and bilirubin less than 2.5 times the upper limit of normal).
  • Normal hematologic function (absolute neutrophil count equal to or greater than 1500/microL, hemoglobin equal to or greater than 9.0 g/dl and platelet count equal to or greater than 100,000/microL).
  • Subjects of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study.

Who cannot join

  • Previous chemotherapy or radiotherapy.
  • Pregnant or breast feeding females because the chemotherapy administered on this trial could have a detrimental effect on the developing fetus or newborn.
  • Histological evidence of tumor infiltration of bone marrow.
  • Stage 1 or 2 embryonal rhabdomyosarcomas.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

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

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. Supportive care measures used in children who are treated with this regimen include mesna to prevent oxazaphosphorine urotoxicity, dexrazoxane to reduce doxorubicin cardiotoxicity, and filgrastim to shorten the duration of neutropenia. The purpose of this randomized open label trial is to 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. 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 and for detailed cardiac studies. High-risk patients who are treated on this front line trial and respond will also be candidates for a planned transplant protocol. A total of 34 patients (17 patients per treatment arm) will be entered onto the trial.

Read the detailed description

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 or equal to 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.
Being tested
Filgrastim, Filgrastim-SD/01
Keywords
AMGEN, Granulocyte Colony-Stimulating Factor, MPNST, Randomized, Sarcoma, Tumor
Medical subject headings
Sarcoma, Ewing, Rhabdomyosarcoma, Neurofibrosarcoma, Sarcoma, Synovial, Sarcoma, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FilgrastimBiological

    5 microgram/kg/dose SC daily starting 24-36 hours after last dose of chemotherapy until post-nadir ANC >=10,000/microliter

  • Filgrastim-SD/01Biological

    100 microgram/kg SC 24-36 hours after last dose of chemotherapy (single dose)

Study groups in NCT00004853
Study groupRoleWhat they receive
1Experimentalsingle dose of intervention after each cycle of Standard 5 drug dose-intensive chemotherapy
Receives: Biological: Filgrastim
2Experimentalsingle dose of interventionafter each cycle of Standard 5 drug dose-intensive chemotherapy
Receives: Biological: Filgrastim-SD/01

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Tolerance and toxicity

    Measured: 1 year

  2. PKs

    Measured: 1 year

Secondary outcomes (6)
  1. Compare neutrophil function

  2. Compare CD34 positive stem cell mobilization

  3. Compare days of febrile neutropenia, days on antibiotics, and inpatient days resulting from neutropenia

  4. Evaluate the role of functional cardiac MRI and serum troponin T levels in detecting early doxorubicin cardiotoxicity

  5. Assess methods of detecting minimal residual disease

  6. cDNA microarray analysis of gene expression, development of cell lines and xenotransplantation models, and exploration of apoptotic pathways

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Mar 2000 (estimated)
  2. Study start3 Mar 2000
  3. Primary completion20 May 2009
  4. Study completion20 May 2009

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
34 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00004853
Sponsor's protocol ID
000092
Other IDs
00-C-0092
Status last verified
27 Jan 2016
First submitted
4 Mar 2000
Last updated
12 Nov 2019
Results posted
No

Publications

  • Delgado C, Francis GE, Fisher D. The uses and properties of PEG-linked proteins. Crit Rev Ther Drug Carrier Syst. 1992;9(3-4):249-304.

    PubMed 1458545
  • Welte K, Gabrilove J, Bronchud MH, Platzer E, Morstyn G. Filgrastim (r-metHuG-CSF): the first 10 years. Blood. 1996 Sep 15;88(6):1907-29. No abstract available.

    PubMed 8822908
  • Layton JE, Hockman H, Sheridan WP, Morstyn G. Evidence for a novel in vivo control mechanism of granulopoiesis: mature cell-related control of a regulatory growth factor. Blood. 1989 Sep;74(4):1303-7.

    PubMed 2475185

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Filgrastim and Filgrastim-SD/01 in people with Ewing's Sarcoma and Rhabdomyosarcoma, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Tolerance and toxicity (time frame: 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00004853, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Nov 2019.

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