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

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.

Status

UNKNOWN

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT01697163

Enrollment

155

Registered

2012-10-02

Start date

2012-10-31

Completion date

2014-09-30

Last updated

2012-10-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

NSCLC

Keywords

De Novo Resistance, Iressa, EGFR mutation, lung cancer

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.

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.

Interventions

None listed

Study design

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

20 Years to 80 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
hazard rates of PFS	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

Measure	Time frame	Description
OS	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)

Contacts

Primary ContactJoo Hang Kim, MD, PhD

kjhang@yuhs.ac82-2-2228-8131

Outcome results