Study of Blood Samples From Patients With Osteosarcoma

Completed

• Conditions: Localized Osteosarcoma; Metastatic Osteosarcoma; Recurrent Osteosarcoma
• Interventions: Other: laboratory biomarker analysis

• Registration Number: NCT00954473
• Lead Sponsor: Children's Oncology Group

Brief Summary

This research trial studies blood samples from patients with osteosarcoma. Studying the genes found in samples of blood from patients with osteosarcoma may help doctors identify biomarkers related to the disease.

Detailed Description

PRIMARY OBJECTIVE:

I. Conduct a large-scale candidate gene association study in osteosarcoma (OS) using cases from the national Children's Oncology Group (COG) OS biology study (P9851 and successor study AOST06B1).

SECONDARY OBJECTIVES:

I. Conduct a genome-wide association study (GWAS) of OS. II. Fine-map genomic regions associated with OS to identify putative functional loci.

III. Conduct whole-exome sequencing of germline OS deoxyribonucleic acid (DNA) samples.

IV. Investigate the functional implications of promising genetic variants associated with OS.

OUTLINE:

Blood samples undergo polymorphism analysis of common single-nucleotide polymorphisms and haplotypes to examine genetic variation, gene-gene interactions, and the population structure.

Study Timeline

• Study Start: 2009-01
• Study First Submitted: 2009-08-06
• Study First Submitted QC: 2009-08-06
• Study First Posted: 2009-08-07
• Status Verified: 2016-05
• Primary Completion: 2016-05
• Last Update Submitted: 2016-05-17
• Last Update Posted: 2016-05-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1000

Inclusion Criteria

• Blood samples collected from clinical trials COG-P9851 and COG-AOST06B1

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Ancillary-correlative (osteosarcoma genetic risk)	laboratory biomarker analysis	Blood samples undergo polymorphism analysis of common single-nucleotide polymorphisms and haplotypes to examine genetic variation, gene-gene interactions, and the population structure.

Primary Outcome Measures

Name	Time	Method
SNPs associated with OS	Baseline	Logistic regression will be used to estimate odds ratios and 95% confidence intervals for the association between each SNP and OS under co-dominant, dominant and recessive genetic models. Stratified analyses will be conducted to examine sex, tumor subtype and outcome differences.
Gene-gene interactions	Baseline	Assessed using a multiplicative model. Haplotypes will be constructed using both Bayesian and expectation-maximization algorithms. Differences between cases and controls will be evaluated with HaploStats which uses haplotype posterior probabilities as weights to update the regression coefficients in an iterative manner.
Hardy-Weinberg equilibrium on all SNPs	Baseline	Determined on all SNPs by chi-square tests.
Whole-exome variant loci	Baseline	Annotation and filtering of each whole-exome variant locus will be performed using a custom software pipeline. Variants in \>= 2 OS cases will be validated, and then subsequently replicated in additional OS cases (samples previously received for the GWAS from international collaborators). Variants will also be evaluated for presence in known biologically plausible pathways and genes.
Survival outcomes	Baseline	Kaplan-Meier survival curves will be used to determine outcome relative to genotype.

Trial Locations

Locations (1)

Children's Oncology Group; 🇺🇸 Arcadia, California, United States