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

• ClinicalTrials.gov Identifier: NCT00048984
• Recruitment Status: Completed
• First Posted: January 27, 2003
• Last Update Posted: June 24, 2013
• Sponsor: Children's Oncology Group
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Children's Oncology Group

Study Description

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.

Condition or disease	Intervention/treatment
Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor	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 Design

• Study Type: Observational
• Actual Enrollment: 637 participants
• Time Perspective: Prospective
• Official Title: A Groupwide Biology and Banking Study for Ewing Sarcoma
• Study Start Date: January 2003
• Actual Primary Completion Date: February 2013

Groups and Cohorts

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

Outcome Measures

Primary Outcome Measures :

1. Event-free survival [ Time Frame: 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 :

1. Success rate in which biomarker analyses can be carried out [ Time Frame: Up to 5 years ]
2. Percent of the population on which biomarker analysis could be successfully conducted [ Time Frame: 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.
3. Percent of submissions on which biomarker analysis could be successfully conducted [ Time Frame: 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.
4. Relation to known prognostic factors including the presence or absence of metastatic disease, the site of disease, and other known risk factors [ Time Frame: 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.

Biospecimen Retention:   Samples With DNA

Paraffin-embedded blocks of tumor tissue or slides of tumor tissue, and blood specimens

Eligibility Criteria

• Ages Eligible for Study: up to 50 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Probability Sample

Study Population

Patients who have Ewing's sarcoma

Criteria

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

Contacts and Locations

Locations

United States, California

Children's Oncology Group

Arcadia, California, United States, 91006-3776

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Daniel West; Children's Oncology Group

More Information

• Responsible Party: Children's Oncology Group
• ClinicalTrials.gov Identifier: NCT00048984
• Obsolete Identifiers: NCT00063271, NCT00228774
• Other Study ID Numbers: AEWS02B1; 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 ); U10CA098543 ( U.S. NIH Grant/Contract )
• First Posted: January 27, 2003
• Last Update Posted: June 24, 2013
• Last Verified: June 2013

Additional relevant MeSH terms:

Neoplasms; Sarcoma; Sarcoma, Ewing; Neuroectodermal Tumors; Neuroectodermal Tumors, Primitive; Neuroectodermal Tumors, Primitive, Peripheral; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neoplasms, Neuroepithelial; Neoplasms, Glandular and Epithelial