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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Children's Oncology Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00904241
First received: May 16, 2009
Last updated: July 23, 2014
Last verified: July 2014

May 16, 2009
July 23, 2014
November 2000
January 2100   (final data collection date for primary outcome measure)
  • Factors currently used for risk-group assignment (DNA content, MYCN copy number, and tumor histology) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    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 2 years ] [ Designated as safety issue: No ]
    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 2 years ] [ Designated as safety issue: No ]
    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 2 years ] [ Designated as safety issue: No ]
    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 2 years ] [ Designated as safety issue: No ]
    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.
  • Database of the known biologic prognostic factors for patients on therapeutic studies [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    During the testing for treatment effect in Phase III trials, the biologic prognostic factors may be needed for adjustment in the Cox regression model-building process.
  • Factors currently used for risk-group assignment (DNA content, MYCN copy number, and tumor histology) [ Designated as safety issue: No ]
  • Prevalence of 1p, 11q, 14q loss of heterozygosity and gain of 17q [ Designated as safety issue: No ]
  • Telomerase activity [ Designated as safety issue: No ]
  • Expression of nerve growth factor and its high affinity (Trk-A) and low affinity (p75NTR) receptors [ Designated as safety issue: No ]
  • 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 [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00904241 on ClinicalTrials.gov Archive Site
  • MYCN status per tumor [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    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 2 years ] [ Designated as safety issue: No ]
    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 2 years ] [ Designated as safety issue: No ]
    Descriptive analysis will be performed.
  • Incidence of spinal cord compression [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Descriptive analysis will be performed.
  • Presentation with multifocal primary tumors [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Descriptive analysis will be performed.
Not Provided
Not Provided
Not Provided
 
Biomarkers in Tumor Tissue Samples From Patients With Newly Diagnosed Neuroblastoma or Ganglioneuroblastoma
Neuroblastoma Biology Studies

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.

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.

Observational
Observational Model: Cohort
Time Perspective: Prospective
Not Provided
Retention:   Samples With DNA
Description:

frozen tumor tissue, Diagnostic bone marrow, Diagnostic blood

Non-Probability Sample

Patients with suspected neuroblastoma, suspected ganglioneuroblastoma, or suspected ganglioneuroma/maturing subtype enrolled on ANBL00B1

  • Disseminated Neuroblastoma
  • Ganglioneuroblastoma
  • Localized Resectable Neuroblastoma
  • Localized Unresectable Neuroblastoma
  • Regional Neuroblastoma
  • Stage 4S Neuroblastoma
  • Other: laboratory biomarker analysis
    Correlative studies
  • Other: cytology specimen collection procedure
    Correlative studies
    Other Name: cytologic sampling
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.
Interventions:
  • Other: laboratory biomarker analysis
  • Other: cytology specimen collection procedure
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
10000
Not Provided
January 2100   (final data collection date for primary outcome measure)

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
  • 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
  • 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
Both
up to 30 Years
No
United States,   Canada,   New Zealand,   Australia,   Puerto Rico,   Switzerland
 
NCT00904241
ANBL00B1, NCI-2009-00397, CDR0000078642, ANBL00B1, ANBL00B1, U10CA180886, U10CA098543
Yes
Children's Oncology Group
Children's Oncology Group
National Cancer Institute (NCI)
Principal Investigator: Michael Hogarty, MD Children's Oncology Group
Children's Oncology Group
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP