Biomarkers in Blood and Tissue Samples From Patients With Newly Diagnosed Neuroblastoma

Neuroblastoma Clinical Trial

Official title:

Neuropeptide Y and Its Receptors in Neuroblastoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01387724
• Other study ID #: ANBL11B1
• Secondary ID: COG-ANBL11B1NCI-
• Status: Completed
• Phase: N/A
• First received: July 1, 2011
• Last updated: May 17, 2016
• Start date: June 2011

Study information

• Verified date: May 2016
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Observational

Clinical Trial Summary

RATIONALE: Studying samples of blood and tissue from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer.

PURPOSE: This research trial studies biomarkers in blood and tissue samples from patients with newly diagnosed neuroblastoma.

Description:

OBJECTIVES:

• Determine the expression of neuropeptide Y (NPY) and its receptors (Rs) in human neuroblastoma (NB) tissues.

• Determine whether BDNF/TrkB and TrkAIII stimulate expression of NPY and its Rs.

• Determine whether NPY mediates BDNF- and TrkAIII-induced NB proliferation and survival.

• Determine neurotrophins' angiogenic actions.

• Identify factors released from NB cells upon NPY stimulation (proteomics).

• Determine whether NPY upregulates expression of the identified proteins in NB and their Rs in endothelial cells (ECs).

• Test whether inhibition of the identified pathways reduces angiogenic activity of NB-conditioned media.

• Determine the mechanisms of NYP actions and signaling pathways.

• Test whether blocking NPY-Y2/Y5 pathway reduces NB growth and vascularization in vivo.

OUTLINE: Archived tumor tissue and serum samples are analyzed for neuropeptide Y and its receptors (Y1, Y2, and Y5) expression, neuroblastoma prognostic factors (MYCN, TrkA, TrkAIII, TrkB, BDNF, and NGF), and angiogenic markers by real-time PCR, IHC, ELISA, radioimmunoassay (RIA), mitogenic assay, caspase 3/7 activity assay, western blots, liquid chromatography, tandem mass spectrometry, proteomic assays, and other assays. Results are then analyzed and compared with patients' clinical data, including stage of disease, its phenotype, prognostic markers, age and gender, and response to treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 300
• Est. primary completion date: May 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year to 10 Years

Eligibility

DISEASE CHARACTERISTICS:

• Children with newly diagnosed neuroblastoma or ganglioneuroblastoma

• Samples from the Children's Oncology Group (COG) from patients enrolled in clinical trials in institutions in the USA, Canada, and Australia

• Paraffin-embedded tumor specimens, RNA isolated from tumor tissues, and patient serum must be available

PATIENT CHARACTERISTICS:

• Not specified

PRIOR CONCURRENT THERAPY:

• Not specified

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Neuroblastoma

Intervention

Genetic:
• RNA analysis

• polymerase chain reaction

• protein expression analysis

• proteomic profiling

• western blotting

Other:
• enzyme-linked immunosorbent assay

• immunohistochemistry staining method

• laboratory biomarker analysis

• liquid chromatography

• mass spectrometry

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Association of high expression of NPY and its Y2/Y5 Rs in NBs with poor outcome of the disease, advanced stage, increased vascularization and other unfavorable prognostic factors, such as TrkB expression and MYCN amplification			No
Primary	BDNF/TrkB and TrkAIII up-regulate expression of NPY and its Rs			No
Primary	NPY upregulates expression of the identified proteins in NB and their Rs in endothelial cells (ECs)			No
Primary	Interaction between Y2 and Y5 receptors in NB and ECs sensitize them to NPY and amplify NPY-induced proliferation			No
Primary	Blocking the NPY-Y2/Y5 pathway reduces NB growth and tumor vascularization			No

External Links

•   Clinical trial summary from the National Cancer Institute's PDQ® database