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

This study is not yet open for participant recruitment.
Verified September 2012 by Severance Hospital
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Joo Hang Kim, Severance Hospital
ClinicalTrials.gov Identifier:
NCT01697163
First received: September 12, 2012
Last updated: September 26, 2012
Last verified: September 2012
History of Changes
  Purpose

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.


Condition
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:

MedlinePlus related topics: Cancer Lung Cancer
U.S. FDA Resources

Further study details as provided by Severance Hospital:

Primary Outcome Measures:
  • hazard rates of PFS [ Time Frame: 1year ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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)
Groups/Cohorts
Iressa
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.

  Eligibility

Ages Eligible for Study:   20 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

NSCLC patient with EGFR mutation

Criteria

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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01697163

Contacts
Contact: Joo Hang Kim, MD, PhD 82-2-2228-8131 kjhang@yuhs.ac

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

No publications provided

Responsible Party: Joo Hang Kim, Severance Hospital
ClinicalTrials.gov Identifier: NCT01697163     History of Changes
Other Study ID Numbers: ISSIRES0067
Study First Received: September 12, 2012
Last Updated: September 26, 2012
Health Authority: Korea: Food and Drug Administration

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

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
 Neoplasms
Lung Diseases
Respiratory Tract Diseases
Mitogens
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 16, 2013