Studying Biomarkers in Samples From Patients With High-Risk Neuroblastoma

Alternative Lengthening of Telomeres (ALT) in Neuroblastoma

RATIONALE: Studying samples of blood and tumor 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 samples from patients with high-risk neuroblastoma.

Study Overview

• Status: Completed
• Conditions: Neuroblastoma
• Intervention / Treatment: Other: medical chart review; Other: laboratory biomarker analysis; Genetic: DNA analysis; Genetic: polymerase chain reaction

Detailed Description

OBJECTIVES:

• To establish telomere length measurement by quantitative polymerase chain reaction (qPCR) as an alternative lengthening of telomeres (ALT) detection method in neuroblastoma (NB).
• To determine the frequency of ALT in high-risk NB and the characteristics of ALT+ NB.
• To establish C-circle (extra-chromosomal telomeric DNA circles) level as a marker of ALT activity in NB.
• To evaluate the prognostic significance of ALT in NB.
• To evaluate the utility of the C-circle assay for the detection of circulating tumor DNA in NB patients with an ALT+ tumor.

OUTLINE: Archived tumor tissue and serum samples are analyzed for telomere length measurement, frequency, and C-circle levels by PCR. Results are then compared with patients' age at diagnosis and outcomes including survival data (event-free and overall survival).

• Study Type: Observational
• Enrollment (Anticipated): 99

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 30 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients diagnosed with neuroblastoma.

Description

DISEASE CHARACTERISTICS:

• Snap-frozen neuroblastoma (NB) tumors collected at diagnosis (Objectives 1 to 3)

  • High-risk stage 3 or 4 NB AND MYCN non-amplified, i.e., exclude stage 4 infants who are not high-risk

    • Up to five high-risk (> 18 months, unfavorable histology) stage 3/MYCN non-amplified tumors
  • Patients preferably treated on protocol COG-A3973 or similar protocols with myeloablative therapy
  • At least 3 years of follow-up for those with no event (current evidence suggests that ALT+ NBs often relapse late, i.e., 2 years or longer from diagnosis)

• NB tumor DNA collected at diagnosis (Objectives 2 & 3)

  • High-risk stage 3 or 4 NB as for Objective 1, except for MYCN status
  • Stage 4 tumors are preferred; may include up to seven high-risk stage 3 tumors with similar distribution of MYCN-amplified and non-amplified tumors

• Frozen serum from NB patients (Objective 5; 2nd stage of project)

  • Paired serum obtained at diagnosis from patients with ALT+ or ALT- tumors identified in Objective 2

PATIENT CHARACTERISTICS:

• Not specified

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
The sensitivity and specificity, as well as the optimal cut-off, for telomere length (TL) qPCR as an ALT detection method
Frequency and characteristics of ALT in high-risk NB
C-circle level as a marker of ALT activity in NB
Prognostic value of ALT
C-circle assay utility in detecting tumor DNA in the serum of NB patients with an ALT

Collaborators and Investigators

• Sponsor: Children's Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Loretta Lau, MD, Sydney Children's Hospitals Network

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): May 1, 2016
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: January 11, 2012
• First Submitted That Met QC Criteria: January 11, 2012
• First Posted (Estimate): January 16, 2012

Study Record Updates

• Last Update Posted (Estimate): May 19, 2016
• Last Update Submitted That Met QC Criteria: May 17, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: localized unresectable neuroblastoma; recurrent neuroblastoma; stage 4S neuroblastoma; regional neuroblastoma; localized resectable neuroblastoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive; Neuroectodermal Tumors, Primitive, Peripheral; Neuroblastoma
• Other Study ID Numbers: ANBL12B5 (Other Identifier: Children's Oncology Group); COG-ANBL12B5 (Other Identifier: Children's Oncology Group); CDR0000722061 (Other Identifier: Clinical Trials.gov); NCI-2012-00109 (Registry Identifier: CTRP (Clinical Trial Reporting Program))