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
  Purpose

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.


Condition
Non Small Cell Lung Cancer

Study Type: Observational
Study Design: Observational Model: Case-Crossover
Time Perspective: Cross-Sectional
Official Title: A Retrospective Study of Biomarkers in Non-small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by National University Hospital, Singapore:

Study Start Date: April 2009
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

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.

Criteria

Inclusion Criteria:

  • Nil

Exclusion Criteria:

  • Nil
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01100840

Contacts
Contact: Ross Andrew Soo, MBBS 65 67724624 ross_soo@nuhs.edu.sg

Locations
Singapore
National University Hospital Recruiting
Singapore, Singapore, 119074
Contact: Ross Andrew Soo, MBBS    65 6772 4624    ross_soo@nuhs.edu.sg   
Principal Investigator: Ross Andrew Soo, MBBS         
Sponsors and Collaborators
National University Hospital, Singapore
Investigators
Principal Investigator: Ross Andrew Soo, MBBS National University Hospital, Singapore
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT01100840     History of Changes
Other Study ID Numbers: NS03/20/08
Study First Received: September 14, 2009
Last Updated: December 10, 2013
Health Authority: Singapore: Domain Specific Review Boards

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on August 27, 2014