Clinical Trials /

Biomarkers in Tumor Tissue Samples From Patients With Newly Diagnosed Neuroblastoma or Ganglioneuroblastoma

NCT00904241

Description:

This research trial studies biomarkers in tumor tissue samples from patients with newly diagnosed neuroblastoma or ganglioneuroblastoma. Studying samples of tumor tissue from patients with cancer in the laboratory may help doctors identify and learn more about biomarkers related to cancer.

Related Conditions:
  • Ganglioneuroblastoma
  • Mature Ganglioneuroma
  • Neuroblastoma
Recruiting Status:

Recruiting

Trial Eligibility

Document

Title

  • Brief Title: Biomarkers in Tumor Tissue Samples From Patients With Newly Diagnosed Neuroblastoma or Ganglioneuroblastoma
  • Official Title: Neuroblastoma Biology Studies

Clinical Trial IDs

  • ORG STUDY ID: ANBL00B1
  • SECONDARY ID: NCI-2009-00397
  • SECONDARY ID: CDR0000078642
  • SECONDARY ID: ANBL00B1
  • SECONDARY ID: ANBL00B1
  • SECONDARY ID: U10CA180886
  • SECONDARY ID: U10CA098543
  • SECONDARY ID: UG1CA189958
  • NCT ID: NCT00904241
  • NCT ALIAS: NCT00256763

Conditions

  • Ganglioneuroblastoma
  • Localized Resectable Neuroblastoma
  • Localized Unresectable Neuroblastoma
  • Regional Neuroblastoma
  • Stage 4 Neuroblastoma
  • Stage 4S Neuroblastoma

Purpose

This research trial studies biomarkers in tumor tissue samples from patients with newly diagnosed neuroblastoma or ganglioneuroblastoma. Studying samples of tumor tissue from patients with cancer in the laboratory may help doctors identify and learn more about biomarkers related to cancer.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To prospectively analyze the factors that are currently used for risk-group assignment
      (v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog [MYCN] copy number
      by fluorescent in situ hybridization [FISH], deoxyribonucleic acid [DNA] content by flow
      cytometry, and tumor histology using the International Neuroblastoma Pathologic
      Classification System) in neuroblastoma tumors at the time of diagnosis.

      II. To maintain a reference bank containing clinically and genetically characterized frozen
      tumor tissue, tumor DNA and ribonucleic acid (RNA), histology slides and paraffin blocks,
      neuroblastoma-derived cell lines, patient serum and paired normal DNA obtained at the time of
      diagnosis, at the time of second-look surgery and at the time of relapse for future research
      studies.

      III. To prospectively analyze 1p, 11q, 14q and 17q allelic status, MYCN copy number by
      quantitative polymerase chain reaction (PCR); and the expression pattern of
      neurotrophin-related genes in diagnostic neuroblastoma tumors, and assay for the presence of
      rare tumor cells in biological specimens by reverse transcription (RT)-PCR; these biological
      variables will be analyzed for independent clinical significance compared to MYCN
      amplification, International Neuroblastoma Staging System (INSS) stage, age, ploidy, and
      histologic variables in predicting either response to treatment or outcome.

      IV. To build a database of the known biologic prognostic factors for patients on therapeutic
      studies.

      V. To serve as a Registry for neuroblastoma patients whose tumors demonstrate clinical and
      genetic features defined as ?Low Risk? for treatment failure in the absence of adjuvant
      therapy.

      SECONDARY OBJECTIVES:

      I. To prospectively analyze the concordance between detection of MYCN amplification in tumor
      samples and quantitative detection of MYCN DNA in serum, and to analyze the prognostic
      significance of MYCN amplification as detected in serum samples.

      II. To build a database that includes information regarding the presentation and natural
      history of neuroblastoma-associated health problems including but not limited to opsoclonus
      myoclonus ataxia (OMA) and/or spinal cord compression.

      OUTLINE:

      Patients undergo collection of blood, tissue, and bone marrow samples for analysis via
      RT-PCR, quantitative PCR, flow cytometry, and FISH.

      After completion of study, patients are followed up periodically.
    

Trial Arms

NameTypeDescriptionInterventions
Ancillary-Correlative (cytology specimen collection)Patients undergo collection of blood, tissue, and bone marrow samples for analysis via RT-PCR, quantitative PCR, flow cytometry, and FISH.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  All newly diagnosed patients with suspected neuroblastoma, suspected
                 ganglioneuroblastoma, or suspected ganglioneuroma/maturing subtype seen at Children's
                 Oncology Group (COG) institutions are eligible for this study
    
                   -  There will be no penalty under any circumstances for enrollment of a patient
                      whose definitive institutional diagnosis, or central review diagnosis, is found
                      to be a tumor other than neuroblastoma, ganglioneuroblastoma, or ganglioneuroma/
                      maturing subtype
    
              -  Patients may not have received chemotherapy prior to enrollment on ANBL00B1 and
                 procurement of study-related tissues with the following exception:
    
                   -  Patients that in the opinion of the treating physician are too ill to undergo
                      pre-treatment tissue biopsy and require EMERGENT chemotherapy may be enrolled on
                      ANBL00B1; documentation of the emergent nature of therapy initiation is required
    
              -  It is required that a good faith effort (documented by specimen tracking) be made to
                 submit a neuroblastoma sample (tumor, metastasis, and/or tumor-involved bone marrow)
                 of sufficient quality for MYCN analysis in the Neuroblastoma Reference Laboratory in
                 order for any newly diagnosed patient to be enrolled on ANBL00B1; this should be
                 obtained prior to initiation of therapy
    
              -  Exceptions
    
                   -  In rare cases, patients may be deemed too ill to undergo pre-treatment tissue
                      biopsy and require EMERGENT therapy; the following eligibility guidelines apply
                      to these cases:
    
                        -  For presumed INSS stage 4S patients: Efforts to submit tumor tissue (e.g.,
                           primary tumor, skin nodule, or metastatic site) within 96 hours of EMERGENT
                           therapy initiation should be made; however, if the child is deemed too
                           unstable for such a procedure they may still be enrolled as long as
                           pre-treatment peripheral blood and serum have been submitted
    
                        -  For all other INSS stages: tumor tissue should be obtained as soon as
                           possible within 96 hours of EMERGENT therapy initiation; patients without
                           tumor tissues submitted within this time-frame are not eligible for
                           enrollment
    
                             -  Note: it may not be possible to obtain all necessary tumor biomarkers
                                for therapy stratification in such cases; if a patient enrolled on
                                ANBL00B1 undergoes an additional diagnostic procedure within 96 hours
                                of initiating therapy, additional tumor specimens may be submitted to
                                obtain biomarkers used for risk classification; the decision to perform
                                such procedures, and/or submit these specimens, is to be made by the
                                managing clinicians and should reflect the clinical need to know the
                                status of such biomarkers
    
                        -  Patients enrolled on ANBL1232 in Group A (either A1 or A2) will not have a
                           tumor biopsy or resection upfront; tumor tissue submission is therefore not
                           required for these patients to enroll on ANBL00B1; a peripheral blood and
                           serum sample is the only specimen required to be submitted for this group of
                           patients; should they undergo a biopsy or resection at a later date tumor
                           can be submitted for biomarker testing at this time
    
              -  All patients and/or their parents or legal guardians must sign a written informed
                 consent
    
              -  All institutional, Food and Drug Administration (FDA), and National Cancer Institute
                 (NCI) requirements for human studies must be met
    
            Exclusion Criteria:
    
              -  Patients with relapsed neuroblastoma who were not enrolled on ANBL00B1 at original
                 diagnosis are NOT eligible; samples should be submitted as part of the ABTR04B1
                 protocol
          
    Maximum Eligible Age:30 Years
    Minimum Eligible Age:N/A
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Factors currently used for risk-group assignment (DNA content, MYCN copy number, and tumor histology)
    Time Frame:Up to 3 years
    Safety Issue:
    Description:Life tables, Kaplan-Meier survival curves, log-rank tests, and Cox regression will be used to explore the relationship of laboratory variables to outcome.

    Secondary Outcome Measures

    Measure:MYCN status per tumor
    Time Frame:Up to 3 years
    Safety Issue:
    Description:Cross tabulations of MYCN status per tumor versus MYCN status per blood will be generated, the percentage concordant and the percentage discordant will be calculated, and receiver operating characteristic (ROC) analyses will be performed. Kaplan-Meier curves of MYCN status per blood will be generated, and a logrank test comparison performed. The prognostic ability of MYCN status per tumor versus MYCN status per blood will be tested in a multivariable Cox model.
    Measure:MYCN status per blood
    Time Frame:Up to 3 years
    Safety Issue:
    Description:Cross tabulations of MYCN status per tumor versus MYCN status per blood will be generated, the percentage concordant and the percentage discordant will be calculated, and ROC analyses will be performed. Kaplan-Meier curves of MYCN status per blood will be generated, and a logrank test comparison performed. The prognostic ability of MYCN status per tumor versus MYCN status per blood will be tested in a multivariable Cox model.
    Measure:Incidence of OMA
    Time Frame:Up to 3 years
    Safety Issue:
    Description:Descriptive analysis will be performed.
    Measure:Incidence of spinal cord compression
    Time Frame:Up to 3 years
    Safety Issue:
    Description:Descriptive analysis will be performed.
    Measure:Presentation with multifocal primary tumors
    Time Frame:Up to 3 years
    Safety Issue:
    Description:Descriptive analysis will be performed.

    Details

    Phase:
    Primary Purpose:Observational
    Overall Status:Recruiting
    Lead Sponsor:Children's Oncology Group

    Last Updated