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

A Groupwide Biology and Banking Study for Ewing Sarcoma

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.

Study Overview

• Status: Completed
• Conditions: Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
• Intervention / Treatment: Other: laboratory biomarker analysis

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 Type: Observational
• Enrollment (Actual): 637

Contacts and Locations

Study Locations

• United States
  • California
    • Arcadia, California, United States, 91006-3776
      • Children's Oncology Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 50 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients who have Ewing's sarcoma

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Basic science (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.

Other: laboratory biomarker analysis; Correlative studies

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-free survival	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.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Success rate in which biomarker analyses can be carried out		Up to 5 years
Percent of the population on which biomarker analysis could be successfully conducted	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.	Up to 5 years
Percent of submissions on which biomarker analysis could be successfully conducted	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.	Up to 5 years
Relation to known prognostic factors including the presence or absence of metastatic disease, the site of disease, and other known risk factors	The prevalence of these risk factors will be determined for the evaluable and nonevaluable samples to ensure the comparability of these two groups.	Up to 5 years

Collaborators and Investigators

• Sponsor: Children's Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Daniel West, Children's Oncology Group

Study record dates

Study Major Dates

• Study Start: January 1, 2003
• Primary Completion (Actual): February 1, 2013

Study Registration Dates

• First Submitted: November 12, 2002
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): June 24, 2013
• Last Update Submitted That Met QC Criteria: June 20, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms; Sarcoma; Sarcoma, Ewing; Neuroectodermal Tumors; Neuroectodermal Tumors, Primitive; Neuroectodermal Tumors, Primitive, Peripheral
• Other Study ID Numbers: AEWS02B1; U10CA098543 (U.S. NIH Grant/Contract); NCI-2012-02494 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); CDR0000257115 (Other Identifier: Clinical Trials.gov); COG-AEWS02B1 (Other Identifier: Children's Oncology Group); NCI-03-C-0216 (Other Identifier: NCI)