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

NSCLC Clinical Trial

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.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01697163
• Other study ID #: ISSIRES0067
• Status: Not yet recruiting
• Phase: N/A
• First received: September 12, 2012
• Last updated: September 26, 2012
• Start date: October 2012
• Est. completion date: September 2014

Study information

• Verified date: September 2012
• Source: Severance Hospital
• Contact: Joo Hang Kim, MD, PhD
• Phone: 82-2-2228-8131
• Email: kjhang[@]yuhs.ac
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 155
• Est. completion date: September 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 80 Years

Eligibility

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.

Study Design

Time Perspective: Prospective

Related Conditions & MeSH terms

• NSCLC

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Severance Hospital	AstraZeneca

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	OS	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)	2years	No
Primary	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	No