Registry for Patients With Acquired Resistance to Small Molecule Kinase Inhibitors in Non-Small-Cell Lung Cancer

This study has been completed.

Sponsor:

Information provided by (Responsible Party):

Memorial Sloan Kettering Cancer Center

ClinicalTrials.gov Identifier:

NCT00579683

First received: December 20, 2007

Last updated: February 3, 2016

Last verified: February 2016

History of Changes

Tracking Information

First Received Date ^ICMJE

December 20, 2007

Last Updated Date

February 3, 2016

Start Date ^ICMJE

August 2004

Primary Completion Date

February 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

To compare EGFR gene sequence in patients upon relapse with EGFR gene sequence prior to treatment with small molecule kinase inhibitors. [ Time Frame: 2 years ]

Original Primary Outcome Measures ^ICMJE

To compare EGFR gene sequence in patients upon relapse with EGFR gene sequence prior to treatment with small molecule kinase inhibitors. [ Time Frame: 12 months ]

Change History

Complete list of historical versions of study NCT00579683 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures ^ICMJE

To identify novel mutations in the tyrosine kinase domain of EGFR in patients with acquired resistance to small molecule kinase inhibitors. [ Time Frame: 2 years ]
To more precisely characterize the frequency and clinical implications of T790M in patients with acquired resistance to small molecule kinase inhibitors. [ Time Frame: 2 years ]
To identify novel mechanisms of acquired resistance to EGFR small molecule kinase inhibitors. [ Time Frame: 2 years ]

Original Secondary Outcome Measures ^ICMJE

Compare EGFR gene copy number in pts progressed after response to sm molecule kinase inhibitors with those pretreatment & identify novel mutations in tyrosine kinase domain of EGFR & characterize frequency of T790M in pts with resistance to inhibitors. [ Time Frame: 12 months ]

Current Other Outcome Measures ^ICMJE

Not Provided

Original Other Outcome Measures ^ICMJE

Not Provided

Descriptive Information

Brief Title ^ICMJE

Registry for Patients With Acquired Resistance to Small Molecule Kinase Inhibitors in Non-Small-Cell Lung Cancer

Official Title ^ICMJE

A Prospective Registry for Patients With Acquired Resistance to Small Molecule Kinase Inhibitors in Non-Small-Cell Lung Cancer

Brief Summary

The purpose of this study is to try to learn more about how small molecule kinase inhibitors work in treating lung cancer. Some early studies have shown that gefitinib, erlotinib and similar drugs are more likely to work if a particular DNA change (also known as a mutation) is found in a protein that is important in lung cancer. This protein is called the epidermal growth factor receptor (EGFR). Since small molecule kinase inhibitors sometimes stop working, we would like to examine your tumor to learn why these medicines are not working as well. Your tumor will be examined for a variety of things including changes in the DNA of the EGFR. We will also sequence parts of the genes for HER2, HER3, HER4, and KRAS, other proteins thought to be important in lung cancer.

Detailed Description

The goal of this protocol is to determine mechanisms of resistance to epidermal growth factor (EGFR) tyrosine kinase inhibitors (EGFR-TKI) in non-small cell lung cancer (NSCLC). A number of trials have shown small molecule kinase inhibitors to be active agents in the treatment of NSCLC [1]. Clinically these drugs have been noted to produce dramatic but infrequent responses. Mutations in the epidermal growth factor receptor have been shown to correlate with sensitivity to gefitinib and erlotinib[2,3]. However, we know that most patients who have initial responses to EGFR-TKI eventually progress. The mechanism of acquired clinical resistance to these inhibitors in patients incompletely understood.

This is a protocol to study clinical characteristics and biopsy tissue of patients with non-small cell lung cancer who have had previous clinical response to small molecule kinase inhibitors and subsequently experience progression of disease. The tissues and other specimens will be used to carry out laboratory studies to explore the molecular basis of sensitivity and resistance to small molecule kinase inhibitors.

Study Type ^ICMJE

Observational

Study Design ^ICMJE

Observational Model: Case-Only
Time Perspective: Prospective

Target Follow-Up Duration

Not Provided

Biospecimen

Retention: Samples With DNA

Description:

Tumor biopsy material will be processed to obtain RNA for analysis of EGFR sequence. Sequencing of additional candidate genes and other studies will follow if sufficient material is available.

Sampling Method

Non-Probability Sample

Study Population

Unresectable or metastatic non-small cell lung cancer (NSCLC)

Condition ^ICMJE

Unresectable or Metastatic Non-small Cell Lung Cancer (NSCLC)

Intervention ^ICMJE

Other: Tumor core biopsy for RNA isolation

RNA isolation will be carried out using approximately 25 mg of gross tissue from these tumor specimens.

Study Groups/Cohorts

This is a protocol to study tissue specimens to identify changes in tumor DNA in NSCLC patients who have previously responded to therapy and who have subsequently experienced disease progression.

Intervention: Other: Tumor core biopsy for RNA isolation

Publications *

Oxnard GR, Arcila ME, Sima CS, Riely GJ, Chmielecki J, Kris MG, Pao W, Ladanyi M, Miller VA. Acquired resistance to EGFR tyrosine kinase inhibitors in EGFR-mutant lung cancer: distinct natural history of patients with tumors harboring the T790M mutation. Clin Cancer Res. 2011 Mar 15;17(6):1616-22. doi: 10.1158/1078-0432.CCR-10-2692. Epub 2010 Dec 6.

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Completed

Enrollment ^ICMJE

228

Completion Date

February 2016

Primary Completion Date

February 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

Inclusion Criteria:

Patients diagnosed with unresectable or metastatic non-small cell lung cancer (NSCLC) and who fulfill the following eligibility criteria will be considered eligible for this study.

Patient must have previously received treatment with small molecule kinase inhibitors targeting at least, in part, EGFR patients may have received other treatments since treatment with small molecule kinase inhibitors including radiation or chemotherapy)
Development of disease progression while actively receiving tyrosine kinase inhibitor
Signed informed consent

Exclusion Criteria:

Sex/Gender

Sexes Eligible for Study:

All

Ages

Child, Adult, Senior

Accepts Healthy Volunteers

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

Listed Location Countries ^ICMJE

United States

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT00579683

Other Study ID Numbers ^ICMJE

04-103

Has Data Monitoring Committee

Not Provided

U.S. FDA-regulated Product

Not Provided

IPD Sharing Statement

Not Provided

Responsible Party

Memorial Sloan Kettering Cancer Center

Study Sponsor ^ICMJE

Memorial Sloan Kettering Cancer Center

Collaborators ^ICMJE

Not Provided

Investigators ^ICMJE

Principal Investigator:

Helena Yu, MD

Memorial Sloan Kettering Cancer Center

PRS Account

Memorial Sloan Kettering Cancer Center

Verification Date

February 2016

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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