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

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ClinicalTrials.gov Identifier: NCT00904241
Recruitment Status : Recruiting
First Posted : May 19, 2009
Last Update Posted : March 24, 2021
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Tracking Information
First Submitted Date May 16, 2009
First Posted Date May 19, 2009
Last Update Posted Date March 24, 2021
Actual Study Start Date November 6, 2000
Estimated Primary Completion Date January 1, 2100   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: October 30, 2014)
  • 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 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 3 years ]
    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.
Original Primary Outcome Measures
 (submitted: May 16, 2009)
  • 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
Change History
Current Secondary Outcome Measures
 (submitted: October 30, 2014)
  • 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 Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Biomarkers in Tumor Tissue Samples From Patients With Newly Diagnosed Neuroblastoma or Ganglioneuroblastoma
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 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.

Study Type Observational
Study Design Not Provided
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population Not Provided
Condition
  • Ganglioneuroblastoma
  • Localized Resectable Neuroblastoma
  • Localized Unresectable Neuroblastoma
  • Regional Neuroblastoma
  • Stage 4 Neuroblastoma
  • Stage 4S Neuroblastoma
Intervention
  • Other: Cytology Specimen Collection Procedure
    Correlative studies
    Other Name: Cytologic Sampling
  • Other: Laboratory Biomarker Analysis
    Correlative studies
Study Groups/Cohorts 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: Cytology Specimen Collection Procedure
  • Other: Laboratory Biomarker Analysis
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: July 23, 2014)
10000
Original Estimated Enrollment
 (submitted: May 16, 2009)
2820
Study Completion Date Not Provided
Estimated Primary Completion Date January 1, 2100   (Final data collection date for primary outcome measure)
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
Sex/Gender
Sexes Eligible for Study: All
Ages up to 30 Years   (Child, Adult)
Accepts Healthy Volunteers No
Contacts
Listed Location Countries Australia,   Canada,   Netherlands,   New Zealand,   Puerto Rico,   Saudi Arabia,   Switzerland,   United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT00904241
Other Study ID Numbers ANBL00B1
NCI-2009-00397 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000078642
ANBL00B1 ( Other Identifier: Childrens Oncology Group )
ANBL00B1 ( Other Identifier: CTEP )
U10CA180886 ( U.S. NIH Grant/Contract )
U10CA098543 ( U.S. NIH Grant/Contract )
UG1CA189958 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Children's Oncology Group
Study Sponsor Children's Oncology Group
Collaborators National Cancer Institute (NCI)
Investigators
Principal Investigator: Michael Hogarty Children's Oncology Group
PRS Account Children's Oncology Group
Verification Date March 2021