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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Neuroblastoma Biology Studies

Brief Summary: 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 Summary:

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 ad
Sponsor: Children's Oncology Group

Current Primary Outcome:

  • Factors currently used for risk-group assignment (DNA content, MYCN copy number, and tumor histology) [ Time Frame: Up to 3 years ]
    Life tables, Kaplan-Meier survival curves, log-rank tests, and Cox regression will be used to explore the relationship of laboratory variables to outcome.
  • Prevalence of 1p, 11q, 14q, and 17q allelic status [ Time Frame: Up to 3 years ]
    These biological variables will be analyzed for independent clinical significance compared to MYCN amplification, INSS stage, age, ploidy, and histologic variables in predicting either response to treatment or outcome.
  • MYCN copy number by quantitative PCR [ Time Frame: Up to 3 years ]
    These biological variables will be analyzed for independent clinical significance compared to MYCN amplification, INSS stage, age, ploidy, and histologic variables in predicting either response to treatment or outcome.
  • Expression pattern of neurotrophin-related genes in diagnostic neuroblastoma tumors [ Time Frame: Up to 3 years ]
    These biological variables will be analyzed for independent clinical significance compared to MYCN amplification, INSS stage, age, ploidy, and histologic variables in predicting either response to treatment or outcome.
  • Presence of rare tumor cells in biological specimens by RT-PCR [ Time Frame: Up to 3 years ]
    These biological variables will be analyzed for independent clinical significance compared to MYCN amplification, INSS stage, age, ploidy, and hist

    Original Primary Outcome:

    • Factors currently used for risk-group assignment (DNA content, MYCN copy number, and tumor histology)
    • Prevalence of 1p, 11q, 14q loss of heterozygosity and gain of 17q
    • Expression of nerve growth factor and its high affinity (Trk-A) and low affinity (p75NTR) receptors
    • Telomerase activity
    • Comparison of the independent clinical significance of biological factors with MYCN amplification, International Neuroblastoma Staging system stage, age, and histologic variables in predicting response to treatment or outcome


    Current Secondary Outcome:

    • MYCN status per tumor [ Time Frame: Up to 3 years ]
      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.
    • MYCN status per blood [ Time Frame: Up to 3 years ]
      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.
    • Incidence of OMA [ Time Frame: Up to 3 years ]
      Descriptive analysis will be performed.
    • Incidence of spinal cord compression [ Time Frame: Up to 3 years ]
      Descriptive analysis will be performed.
    • Presentation with multifocal primary tumors [ Time Frame: Up to 3 years ]
      Descriptive analysis will be performed.


    Original Secondary Outcome:

    Information By: Children's Oncology Group

    Dates:
    Date Received: May 16, 2009
    Date Started: November 2000
    Date Completion:
    Last Updated: April 11, 2017
    Last Verified: April 2017