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

Tracking Information
First Submitted Date	December 20, 2007
First Posted Date	December 24, 2007
Last Update Posted Date	February 4, 2016
Study Start Date	August 2004
Actual Primary Completion Date	February 2016 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures; (submitted: June 12, 2009)	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; (submitted: December 20, 2007)	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; (submitted: March 9, 2011)	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; (submitted: December 20, 2007)	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	Not Provided
Original Other Outcome Measures	Not Provided
Descriptive Information
Brief Title	Registry for Patients With Acquired Resistance to Small Molecule Kinase Inhibitors in Non-Small-Cell Lung Cancer
Official Title	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	Observational
Study Design	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	Unresectable or Metastatic Non-small Cell Lung Cancer (NSCLC)
Intervention	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	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
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	Completed
Actual Enrollment; (submitted: February 3, 2016)	228
Original Estimated Enrollment; (submitted: December 20, 2007)	80
Actual Study Completion Date	February 2016
Actual Primary Completion Date	February 2016 (Final data collection date for primary outcome measure)
Eligibility Criteria	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, Older Adult
Accepts Healthy Volunteers	No
Contacts	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries	United States
Removed Location Countries
Administrative Information
NCT Number	NCT00579683
Other Study ID Numbers	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	Memorial Sloan Kettering Cancer Center
Collaborators	Not Provided
Investigators	Principal Investigator: Helena Yu, MD Memorial Sloan Kettering Cancer Center
PRS Account	Memorial Sloan Kettering Cancer Center
Verification Date	February 2016