Lung Cancer
Conditions
Keywords
recurrent non-small cell lung cancer, stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer
Brief summary
RATIONALE: Studying samples of blood and tissue from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and RNA and identify biomarkers related to cancer. PURPOSE: This laboratory study is looking at biomarkers in tumor tissue and blood samples from patients with non-small cell lung cancer.
Detailed description
OBJECTIVES: Primary * Identify mutations in epidermal growth factor receptor (EGFR) in non-small cell lung cancer specimens from clinical trial CASE-2507. * Investigate EGFR DNA copy-number changes. * Determine abnormalities of other pathways, such as the c-MET and PI3K pathways as potential mechanisms of resistance. OUTLINE: This is a multicenter study. DNA and RNA are extracted from tumor samples. Genomic DNA is analyzed using real-time PCR/ reverse transcriptase PCR analysis and/or FISH analysis in order to study resistance mechanisms such as secondary EGFR mutations and the c-MET and PI3K pathways. RNA is analyzed using TaqMan quantitative PCR in order to determine the copy number of EGFR expressed in these tissues. Peripheral blood samples are used to isolate peripheral blood mononuclear cells positive for epithelial cell adhesion molecule (EpCAM).
Interventions
GENETICDNA analysis
DNA is extracted from tumor samples. Genomic DNA is analyzed using real-time PCR/ reverse transcriptase PCR analysis and/or FISH analysis in order to study resistance mechanisms such as secondary EGFR mutations and the c-MET and PI3K pathways.
GENETICRNA analysis
RNA is extracted from tumor samples. RNA is analyzed using TaqMan quantitative PCR in order to determine the copy number of EGFR expressed in these tissues. Peripheral blood samples are used to isolate peripheral blood mononuclear cells positive for epithelial cell adhesion molecule (EpCAM).
GENETICfluorescence in situ hybridization
DNA and RNA are extracted from tumor samples. Genomic DNA is analyzed using real-time PCR/ reverse transcriptase PCR analysis and/or FISH analysis in order to study resistance mechanisms such as secondary EGFR mutations and the c-MET and PI3K pathways. RNA is analyzed using TaqMan quantitative PCR in order to determine the copy number of EGFR expressed in these tissues. Peripheral blood samples are used to isolate peripheral blood mononuclear cells positive for epithelial cell adhesion molecule (EpCAM).
GENETICgene expression analysis
DNA and RNA are extracted from tumor samples. Genomic DNA is analyzed using real-time PCR/ reverse transcriptase PCR analysis and/or FISH analysis in order to study resistance mechanisms such as secondary EGFR mutations and the c-MET and PI3K pathways. RNA is analyzed using TaqMan quantitative PCR in order to determine the copy number of EGFR expressed in these tissues. Peripheral blood samples are used to isolate peripheral blood mononuclear cells positive for epithelial cell adhesion molecule (EpCAM).
GENETICmutation analysis
DNA and RNA are extracted from tumor samples. Genomic DNA is analyzed using real-time PCR/ reverse transcriptase PCR analysis and/or FISH analysis in order to study resistance mechanisms such as secondary EGFR mutations and the c-MET and PI3K pathways. RNA is analyzed using TaqMan quantitative PCR in order to determine the copy number of EGFR expressed in these tissues. Peripheral blood samples are used to isolate peripheral blood mononuclear cells positive for epithelial cell adhesion molecule (EpCAM).
GENETICpolymerase chain reaction
DNA and RNA are extracted from tumor samples. Genomic DNA is analyzed using real-time PCR/ reverse transcriptase PCR analysis and/or FISH analysis in order to study resistance mechanisms such as secondary EGFR mutations and the c-MET and PI3K pathways. RNA is analyzed using TaqMan quantitative PCR in order to determine the copy number of EGFR expressed in these tissues. Peripheral blood samples are used to isolate peripheral blood mononuclear cells positive for epithelial cell adhesion molecule (EpCAM).
GENETICreverse transcriptase-polymerase chain reaction
DNA and RNA are extracted from tumor samples. Genomic DNA is analyzed using real-time PCR/ reverse transcriptase PCR analysis and/or FISH analysis in order to study resistance mechanisms such as secondary EGFR mutations and the c-MET and PI3K pathways. RNA is analyzed using TaqMan quantitative PCR in order to determine the copy number of EGFR expressed in these tissues. Peripheral blood samples are used to isolate peripheral blood mononuclear cells positive for epithelial cell adhesion molecule (EpCAM).
OTHERlaboratory biomarker analysis
DNA and RNA are extracted from tumor samples. Genomic DNA is analyzed using real-time PCR/ reverse transcriptase PCR analysis and/or FISH analysis in order to study resistance mechanisms such as secondary EGFR mutations and the c-MET and PI3K pathways. RNA is analyzed using TaqMan quantitative PCR in order to determine the copy number of EGFR expressed in these tissues. Peripheral blood samples are used to isolate peripheral blood mononuclear cells positive for epithelial cell adhesion molecule (EpCAM).
Sponsors
National Cancer Institute (NCI)
Case Comprehensive Cancer Center
Study design
Observational model
CASE_ONLY
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Eligible for and concurrently enrolled on clinical trial CASE-2507 PATIENT CHARACTERISTICS: * Willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures * Normal coagulation profile and platelet count \> 100,000/mm³\* * Not pregnant NOTE: \*For patients who have not had a second biopsy procedure already at the time of progression on erlotinib hydrochloride therapy and require a research biopsy. PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No concurrent anticoagulants (e.g., warfarin or low-molecular weight heparin) * No concurrent antiplatelet therapy (e.g., aspirin, clopidogrel, or other antiplatelet agents)\* NOTE: \*For patients who have not had a second biopsy procedure already at the time of progression on erlotinib hydrochloride therapy and require a research biopsy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Predictive value of T790M mutation status of the second biopsy (before maintenance therapy on CASE-2507) on progression-free survival (PFS) | At the time of the second biopsy or surgical procedures |
| Difference of PFS between those with and without T790M mutation | At the time of the second biopsy or surgical procedures |
| Difference of clinical response rate between T790M mutation statuses | At the time of the second biopsy or surgical procedures |
| Predictive value of mutation status on clinical response | At the time of the second biopsy or surgical procedures |
| Association between T790M mutation and baseline clinical-pathological factors and smoking status | At the time of the second biopsy or surgical procedures |
Outcome results
None listed