Afatinib Genomic Landscape
| Status: | Terminated |
|---|---|
| Conditions: | Lung Cancer, Lung Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/17/2018 |
| Start Date: | June 11, 2015 |
| End Date: | February 28, 2018 |
Genomic Landscape of EGFR Mutant NSCLC Prior to Afatinib and at the Time of Disease Progression Following Afatinib
The investigators propose to conduct a pilot feasibility study of single agent afatinib in
patients with previously untreated metastatic EGFR (epidermal growth factor receptor) mutant
adenocarcinoma of the lung (NSCLC = non-small cell lung cancer) with the sole purpose of
characterizing the genomic landscape before afatinib and at the time of disease progression.
patients with previously untreated metastatic EGFR (epidermal growth factor receptor) mutant
adenocarcinoma of the lung (NSCLC = non-small cell lung cancer) with the sole purpose of
characterizing the genomic landscape before afatinib and at the time of disease progression.
The current proposal will include exome and transcriptome sequencing from blood collected at
baseline along with tumor samples obtained prior to starting afatinib and at the time of
disease progression (a total of two tissue samples and one blood sample per patient). The
samples will be collected via consent to the IRB (Institutional Review Board) approved
banking study "Tissue and Blood Acquisition for Genomic Analysis and Collection of Health
Information from Patients with Thoracic Malignancies, Suspected Thoracic Malignancies, or
Mesothelioma".
If carried out successfully, the proposed strategy very likely will lead to a larger and
adequately powered study (perhaps using whole genome sequencing) to understand fully evolving
molecular changes due to clonal selection under treatment pressure. The pace of progress in
the field of sequencing technology currently underway is only likely to accelerate in the
near future yielding richer and highly content-rich information. Moreover, it is likely that
genomic information from DNA sequencing and transcriptome will be supplemented by analyses of
translatomes and proteomes.
Successful completion of the proposed study would enable future studies to fully harness the
potential of emerging technologies to develop novel approaches to treat and even ideally
prevent resistance to EGFR TKIs (tyrosine-kinase inhibitor) and other molecularly targeted
therapies. This could serve as a template for other cancer types as well. Over time, this
approach, broadly used, would create simultaneously, highly valuable annotated tumor
specimens along with germ line DNA for high-throughput genomic studies to identify novel
targets and their impact on the course of disease. Re-analyzing molecular changes in the
tumor at the time of disease progression would likely be a new standard of care to guide
salvage therapy.
baseline along with tumor samples obtained prior to starting afatinib and at the time of
disease progression (a total of two tissue samples and one blood sample per patient). The
samples will be collected via consent to the IRB (Institutional Review Board) approved
banking study "Tissue and Blood Acquisition for Genomic Analysis and Collection of Health
Information from Patients with Thoracic Malignancies, Suspected Thoracic Malignancies, or
Mesothelioma".
If carried out successfully, the proposed strategy very likely will lead to a larger and
adequately powered study (perhaps using whole genome sequencing) to understand fully evolving
molecular changes due to clonal selection under treatment pressure. The pace of progress in
the field of sequencing technology currently underway is only likely to accelerate in the
near future yielding richer and highly content-rich information. Moreover, it is likely that
genomic information from DNA sequencing and transcriptome will be supplemented by analyses of
translatomes and proteomes.
Successful completion of the proposed study would enable future studies to fully harness the
potential of emerging technologies to develop novel approaches to treat and even ideally
prevent resistance to EGFR TKIs (tyrosine-kinase inhibitor) and other molecularly targeted
therapies. This could serve as a template for other cancer types as well. Over time, this
approach, broadly used, would create simultaneously, highly valuable annotated tumor
specimens along with germ line DNA for high-throughput genomic studies to identify novel
targets and their impact on the course of disease. Re-analyzing molecular changes in the
tumor at the time of disease progression would likely be a new standard of care to guide
salvage therapy.
Inclusion Criteria/Exclusion Criteria:
- Diagnosis of metastatic stage IIIB/IV lung adenocarcinoma
- Presence of known sensitizing mutations in EGFR TK domain (exon 19 deletion and L858R)
- Absence of known resistant mutations in the EGFR TK domain (T790M)
- Consented to HRPO # 201305031 ("Tissue and Blood Acquisition for Genomic Analysis and
Collection of Health Information from Patients with Thoracic Malignancies, Suspected
Thoracic Malignancies, or Mesothelioma")
- No prior treatment for this malignancy
- No prior localized therapy to the biopsy site
- Planned treatment with standard of care afatinib at 40 mg QD (daily)
- Not pregnant or breastfeeding
- At least 18 years of age
We found this trial at
1
site
660 S Euclid Ave
Saint Louis, Missouri 63110
Saint Louis, Missouri 63110
(314) 362-5000
Phone: 314-362-5737
Washington University School of Medicine Washington University Physicians is the clinical practice of the School...
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