Try our beta test site
IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...

De Novo Resistance to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified September 2012 by Severance Hospital.
Recruitment status was:  Not yet recruiting
Information provided by (Responsible Party):
Joo Hang Kim, Severance Hospital Identifier:
First received: September 12, 2012
Last updated: September 26, 2012
Last verified: September 2012

This study is based on the following hypothesis "De novo resistance to EGFR-TKI in EGFR mutation positive patients is related with mutations in EGFR downstream genes".

Investigators will prospectively collect genomic DNA and clinical data regarding treatment outcomes to EGFR-TKI in NSCLC patients with activating EGFR mutations. Investigators will sequence candidate mutations of EGFR downstream genes and analyze c-met gene amplification and protein expression in PTEN, HGF, and IGFR. To identify genetic mutations, amplification, and protein over expression as predictive markers of treatment outcomes, investigators analyzed the association of treatment outcomes with the presence of genetic alteration or protein over expression. Investigators will attempt to identify biomarkers that are able to predict de novo resistance to EGFR-TKI in EGFR mutated NSCLC.


Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Pilot Study to Identify the Mechanism of De Novo Resistance to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors (EGFR-TKIs) in NSCLC With EGFR Mutation.

Resource links provided by NLM:

Further study details as provided by Severance Hospital:

Primary Outcome Measures:
  • hazard rates of PFS [ Time Frame: 1year ]
    The primary objective is to compare hazard rates of PFS in patients treated with Iressa between with and without any molecular aberrancy in EGFR-downstream genes/proteins.

Other Outcome Measures:
  • OS [ Time Frame: 2years ]
    Overall survival (OS) of EGFR-TKI according to each biomarker (i.e. PIK3CA, AKT, PTEN, and STK11 mutation and HGF, c-met, and IGFR amplification) Disease control rate (DCR) of EGFR-TKI according to each biomarker (i.e. PIK3CA, AKT, PTEN, and STK11 mutation and HGF, c-met, and IGFR amplification) Progression-free survival (PFS) of EGFR-TKI according to each biomarker (i.e. PIK3CA, AKT, PTEN, and STK11 mutation and HGF, c-met, and IGFR amplification)

Biospecimen Retention:   Samples With DNA
DNA extracted from FFPE tissue sample

Estimated Enrollment: 155
Study Start Date: October 2012
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Lung cancer patients with EGFR mutation

Detailed Description:
Investigators will prospectively enroll patients who match the following criteria: pathologically proven unresectable NSCLC, planning to treat with EGFR-TKI, patients with activating EGFR mutations, and available tissue sample for DNA extraction.

Ages Eligible for Study:   20 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
NSCLC patient with EGFR mutation

Inclusion Criteria:

  1. Pathologically proven unresectable NSCLC
  2. 20 years of age or older
  3. Planned treatment with Iressa®
  4. Patients with activating EGFR mutation (del 19, L858R)
  5. Available detailed smoking history
  6. Available tissue samples (archival tissue) for mutational or molecular analysis (representative paraffin block or unstained sections from tumor diagnostic specimen are mandatory)
  7. Available blood sample
  8. At least one lesion that is measurable according to the RECIST 1.1 criteria by CT or MRI
  9. Written informed consent

Exclusion Criteria:

  1. More than 3rd line treatment
  2. Previously treated with other EGFR-TKI
  3. Life expectancy of less than 12 weeks
  4. Pregnant or lactating female
  5. Any unresolved toxicity greater than CTC grade 2 (version 4.0) from previous anti cancer treatment.
  6. Unsuitable patient in this treatment as determined by doctor.
  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 identifier: NCT01697163

Contact: Joo Hang Kim, MD, PhD 82-2-2228-8131

Sponsors and Collaborators
Severance Hospital
Principal Investigator: Joo Hang Kim, MD, PhD Severance Hospital
  More Information

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Joo Hang Kim, Severance Hospital Identifier: NCT01697163     History of Changes
Other Study ID Numbers: ISSIRES0067
Study First Received: September 12, 2012
Last Updated: September 26, 2012

Keywords provided by Severance Hospital:
De Novo Resistance
EGFR mutation
lung cancer

Additional relevant MeSH terms:
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action processed this record on April 28, 2017