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

NCT01697163 | Unknown

• 1 other identifier: ISSIRES0067
• Study Type: observational
• Target: 155
• Locations: 0 countries
• Sites: N/A

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.

Conditions

NSCLC

Keywords

De Novo Resistance; Iressa; EGFR mutation; lung cancer

Outcome Measures

Primary Outcomes (1)

• hazard rates of PFS

  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.

  1year

Other Outcomes (1)

• OS

  2years

Study Arms (1)

Iressa

Lung cancer patients with EGFR mutation

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

NSCLC patient with EGFR mutation

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Severance Hospital: lead
• AstraZeneca: collaborator

Related Publications (1)

• Lim SM, Kim HR, Cho EK, Min YJ, Ahn JS, Ahn MJ, Park K, Cho BC, Lee JH, Jeong HC, Kim EK, Kim JH. Targeted sequencing identifies genetic alterations that confer primary resistance to EGFR tyrosine kinase inhibitor (Korean Lung Cancer Consortium). Oncotarget. 2016 Jun 14;7(24):36311-36320. doi: 10.18632/oncotarget.8904.

  PMID: 27121209 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

DNA extracted from FFPE tissue sample

MeSH Terms

Conditions

Lung Neoplasms

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Joo Hang Kim, MD, PhD

  Severance Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joo Hang Kim, MD, PhD

CONTACT

82-2-2228-8131; kjhang@yuhs.ac

Study Design

• Study Type: observational
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Severance Hospital

Study Record Dates

• First Submitted: September 12, 2012
• First Posted: October 2, 2012
• Study Start: October 1, 2012
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: October 2, 2012

Record last verified: 2012-09