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

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ClinicalTrials.gov Identifier: NCT01697163
Recruitment Status : Unknown
Verified September 2012 by Joo Hang Kim, Severance Hospital.
Recruitment status was:  Not yet recruiting
First Posted : October 2, 2012
Last Update Posted : October 2, 2012
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Joo Hang Kim, Severance Hospital

Brief Summary:

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 or disease
NSCLC

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.

Study Type : Observational
Estimated Enrollment : 155 participants
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.
Study Start Date : October 2012
Estimated Primary Completion Date : September 2014
Estimated Study Completion Date : September 2014

Resource links provided by the National Library of Medicine

Drug Information available for: Urogastrone

Group/Cohort
Iressa
Lung cancer patients with EGFR mutation



Primary Outcome Measures :
  1. 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:
  1. 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


Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Joo Hang Kim, Severance Hospital
ClinicalTrials.gov Identifier: NCT01697163     History of Changes
Other Study ID Numbers: ISSIRES0067
First Posted: October 2, 2012    Key Record Dates
Last Update Posted: October 2, 2012
Last Verified: September 2012

Keywords provided by Joo Hang Kim, Severance Hospital:
De Novo Resistance
Iressa
EGFR mutation
lung cancer

Additional relevant MeSH terms:
Mitogens
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action