A Retrospective Study of Biomarkers in Non-Small Cell Lung Cancer
Recruitment status was Recruiting
|First Received Date ICMJE||September 14, 2009|
|Last Updated Date||April 7, 2010|
|Start Date ICMJE||April 2009|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT01100840 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||A Retrospective Study of Biomarkers in Non-Small Cell Lung Cancer|
|Official Title ICMJE||A Retrospective Study of Biomarkers in Non-small Cell Lung Cancer|
The purpose of this study is:
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.
|Detailed Description||Not Provided|
|Study Type ICMJE||Observational|
|Study Design ICMJE||Observational Model: Case-Crossover
Time Perspective: Cross-Sectional
|Target Follow-Up Duration||Not Provided|
|Sampling Method||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.
|Condition ICMJE||Non Small Cell Lung Cancer|
|Intervention ICMJE||Not Provided|
|Study Group/Cohort (s)||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Enrollment ICMJE||Not Provided|
|Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Accepts Healthy Volunteers||No|
|Location Countries ICMJE||Singapore|
|NCT Number ICMJE||NCT01100840|
|Other Study ID Numbers ICMJE||NS03/20/08|
|Has Data Monitoring Committee||No|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National University Hospital, Singapore|
|Collaborators ICMJE||Not Provided|
|Information Provided By||National University Hospital, Singapore|
|Verification Date||April 2010|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP