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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00579683
First received: December 20, 2007
Last updated: May 6, 2014
Last verified: May 2014

December 20, 2007
May 6, 2014
August 2004
August 2015   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00579683 on ClinicalTrials.gov Archive Site
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • To identify novel mechanisms of acquired resistance to EGFR small molecule kinase inhibitors. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Registry for Patients With Acquired Resistance to Small Molecule Kinase Inhibitors in Non-Small-Cell Lung Cancer
A Prospective Registry for Patients With Acquired Resistance to Small Molecule Kinase Inhibitors in Non-Small-Cell Lung Cancer

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.

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.

Observational
Observational Model: Case-Only
Time Perspective: Prospective
Not Provided
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.

Non-Probability Sample

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

Unresectable or Metastatic Non-small Cell Lung Cancer (NSCLC)
Other: Tumor core biopsy for RNA isolation
RNA isolation will be carried out using approximately 25 mg of gross tissue from these tumor specimens.
1
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
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.
 
Recruiting
400
August 2015
August 2015   (final data collection date for primary outcome measure)

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:

  • None
Both
Not Provided
No
Contact: Helena Yu, MD 646-888-4274
Contact: Mark Kris, MD 646-888-4197
United States
 
NCT00579683
04-103
Not Provided
Memorial Sloan-Kettering Cancer Center
Memorial Sloan-Kettering Cancer Center
Not Provided
Principal Investigator: Helena Yu, MD Memorial Sloan-Kettering Cancer Center
Memorial Sloan-Kettering Cancer Center
May 2014

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