A Retrospective Study of Biomarkers in Non-Small Cell Lung Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by National University Hospital, Singapore
Sponsor:
Information provided by:
National University Hospital, Singapore
ClinicalTrials.gov Identifier:
NCT01100840
First received: September 14, 2009
Last updated: December 10, 2013
Last verified: December 2013

September 14, 2009
December 10, 2013
April 2009
April 2014   (final data collection date for primary outcome measure)
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Complete list of historical versions of study NCT01100840 on ClinicalTrials.gov Archive Site
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A Retrospective Study of Biomarkers in Non-Small Cell Lung Cancer
A Retrospective Study of Biomarkers in Non-small Cell Lung Cancer

The purpose of this study is:

  1. To characterize the types and frequency of molecular alterations to the epidermal growth factor receptor (EGFR) pathway, FGFR4 and EML-ALK in Asian patients with non-small cell lung cancer
  2. To identify candidate biomarkers of importance in the EGFR and estrogen pathways

Most, if not all, human malignancies including lung cancer are caused by somatic alterations of the genome, leading to activation of oncogenes or inactivation of tumor suppressor genes and their resultant oncogenic effects. In addition to mutations, increased chromosomal copy number (by amplification or polysomy) and DNA methylation are other mechanisms of oncogene activation and tumour suppressor gene inactivation respectively.

Little is known about the relationship between these oncogenes of the EGFR family and the recently described oncogenes FGFR4 and fusion gene EML4-ALK. Recent data suggests molecularly defined subgroups of non-small cell lung cancer (NSCLC) exist and can be used to predict for sensitivity to targeted agents (erlotinib or gefitinib) or cytotoxic chemotherapy (pemetrexate, gemcitabine, platinum agents). The findings that estrogen receptors are present in lung tumours and that estrogen can stimulate growth and proliferation of lung cancers in vitro and in vivo are provocative. Further studies to evaluate the role of estrogens and other sex hormones in lung cancer are warranted.

A further understanding of the molecular indicators of lung cancer prognosis and treatment prediction would improve drug development and patient treatment selection.

Archived paraffin-embedded and fresh frozen NSCLC tumor tissue will be obtained via the Department of Pathology and the National University Tissue Repository respectively. Clinico-pathological characteristics will be obtained from the case records, Pathology and Tissue Repository. DNA will be isolated using standard techniques. Sequencing of genes in the EGFR signaling pathway: EGFR, KRAS, ErbB2, ErbB3, MET, PI3K, and BRAF as well as FGFR4. Unstained slides from the paraffin-embedded tissue will be obtained and subjected to fluoresce in vitro hybridization (FISH) for breakpoints in the EML4 and ALK genes as previously described. For cases that have been snap-frozen, RNA will be extracted and EML4-ALK fusions will be confirmed using RT-PCR and pre-specified primers. To analyse the expression of proteins of putative relevance to EGFR function (such as EGFR, ErbB2, ErbB3, AKT, MET, STAT, ERK, MAPK, cyclin D1, C/EBPa), downstream effects of EGFR: cell proliferation (Ki-67), angiogenesis (CD34, VEGF-A), apoptosis (bcl-2), metastasis, and hormonal influence (oestrogen and progesterone receptors, aromatase), TMA technology will be utilised. The status of the tumor suppressor genes PTEN and C/EBPa will be analysed.

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Observational
Observational Model: Case-Crossover
Time Perspective: Cross-Sectional
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Probability Sample

Archived paraffin-embedded and fresh frozen NSCLC tumor tissue will be obtained via the Department of Pathology at Tan Tock Seng Hospital and National University Hospital and the National University Tissue Repository respectively. Clinico-pathological characteristics will be obtained from the case records, Pathology and Tissue Repository.

Non Small Cell Lung Cancer
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
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April 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Nil

Exclusion Criteria:

  • Nil
Both
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No
Contact: Ross Andrew Soo, MBBS 65 67724624 ross_soo@nuhs.edu.sg
Singapore
 
NCT01100840
NS03/20/08
No
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National University Hospital, Singapore
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Principal Investigator: Ross Andrew Soo, MBBS National University Hospital, Singapore
National University Hospital, Singapore
December 2013

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