Diagnostic Study of Tumor Characteristics in Patients With Ewing's Sarcoma

Completed

• Conditions: Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
• Interventions: Other: laboratory biomarker analysis

• Registration Number: NCT00048984
• Lead Sponsor: Children's Oncology Group

Brief Summary

Diagnostic trial to study genetic differences in patients who have Ewing's sarcoma. Genetic testing may help predict how cancer will respond to treatment and allow doctors to plan more effective therapy.

Detailed Description

PRIMARY OBJECTIVES:

I. To develop a mechanism to collect and distribute tumor specimens to various investigators, and a system to prioritize and develop quality-control measures for central data reporting of studies undertaken.

II. To determine the prognostic significance of translocation subtype in Ewing sarcoma; to determine the prognostic significance of translocation negative Ewing sarcoma.

III. To determine the prognostic significance of MRD detection in bone marrow specimens by RT-PCR determination of EWS-ETS fusion genes.

IV. To determine whether serum levels of IGF1, IGFBP3 are of significance in the outcome of patients with Ewing sarcoma.

V. To determine whether RNA expression profiles performed on diagnostic specimens will allow for the identification of newer prognostic categories and potentially new molecular targets for treatment in Ewing sarcoma.

VI. To identify new treatment targets for therapy. Further testing of these potential targets will be carried out in hopes of expediting translation of these findings to the clinic.

VII. To establish a bank of Ewing sarcoma xenografts in SCID/Beige mice. VIII. To establish clinical proteomics as a resource for investigations of altered signaling molecules in the pathogenesis of Ewing sarcoma.

OUTLINE: This is a multicenter study.

Patients undergo various specimen collections, including bone marrow aspirate, paraffin-embedded blocks of tumor tissue or slides of tumor tissue, and blood specimens. These specimens are collected before, during, and after any chemotherapy regimens, during follow-up, and at time of recurrence. Translocation studies are performed on specimens to identify fusion genes, specifically EWS-ETS. Serum IGF1 and IFGBP3 levels are determined. Bone marrow is assessed for minimal residual disease using reverse-transcriptase polymerase chain reaction.

Study Timeline

• Study First Submitted: 2002-11-12
• Study Start: 2003-01
• Study First Submitted QC: 2003-01-26
• Study First Posted: 2003-01-27
• Primary Completion: 2013-02
• Status Verified: 2013-06
• Last Update Submitted: 2013-06-20
• Last Update Posted: 2013-06-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 637

Inclusion Criteria

• Newly diagnosed or recurrent Ewing's sarcoma

• Availability of the following specimens:

  • Paraffin-embedded block or 20 unstained slides and 1-3 thick (50 micron) sections from initial biopsy
  • Pretreatment serum and whole blood

• Concurrent therapy is not required

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Basic science (biomarker analysis)	laboratory biomarker analysis	Patients undergo various specimen collections, including bone marrow aspirate, paraffin-embedded blocks of tumor tissue or slides of tumor tissue, and blood specimens. These specimens are collected before, during, and after any chemotherapy regimens, during follow-up, and at time of recurrence. Translocation studies are performed on specimens to identify fusion genes, specifically EWS-ETS. Serum IGF1 and IFGBP3 levels are determined. Bone marrow is assessed for minimal residual disease using reverse-transcriptase polymerase chain reaction.

Primary Outcome Measures

Name	Time	Method
Event-free survival	1 year	Univariate analysis using the proportional-hazards regression model will be used to formally assess the prognostic significance of each biological characteristic as it relates to risk for adverse event. Methods such as recursive partitioning adapted to survival analysis will be used to explore possible interactions between the presence of various markers and risk for adverse event.

Secondary Outcome Measures

Name	Time	Method
Relation to known prognostic factors including the presence or absence of metastatic disease, the site of disease, and other known risk factors	Up to 5 years	The prevalence of these risk factors will be determined for the evaluable and nonevaluable samples to ensure the comparability of these two groups.
Success rate in which biomarker analyses can be carried out	Up to 5 years
Percent of submissions on which biomarker analysis could be successfully conducted	Up to 5 years	Determined by the number of patients on whom a definitive analytic result could be obtained, divided by the total number of patients for whom a specimen was submitted for the relevant assay.
Percent of the population on which biomarker analysis could be successfully conducted	Up to 5 years	Determined by the number of patients on whom a definitive analytic result could be obtained, divided by the total number of patients enrolled after the test became part of the routine battery used by the investigators.

Trial Locations

Locations (1)

Children's Oncology Group; 🇺🇸 Arcadia, California, United States