Clinical trial NCT00579683: 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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Unresectable or Metastatic Non-small Cell Lung Cancer (NSCLC)
Keywords: non-small cell lung cancer
NSCLC
metastatic disease
resistent disease
RNA analysis
04-103
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
First posted: 2007-12-24
Enrollment: 228
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Unresectable or metastatic non-small cell lung cancer (NSCLC)

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.

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:

* None

Primary outcomes:
measure: To compare EGFR gene sequence in patients upon relapse with EGFR gene sequence prior to treatment with small molecule kinase inhibitors.
timeFrame: 2 years
Secondary outcomes:
measure: To identify novel mutations in the tyrosine kinase domain of EGFR in patients with acquired resistance to small molecule kinase inhibitors.
timeFrame: 2 years
measure: To more precisely characterize the frequency and clinical implications of T790M in patients with acquired resistance to small molecule kinase inhibitors.
timeFrame: 2 years
measure: To identify novel mechanisms of acquired resistance to EGFR small molecule kinase inhibitors.
timeFrame: 2 years
Other outcomes:
Locations:
city: Basking Ridge
country: United States
facility: Memoral Sloan Kettering Cancer Center
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan-Kettering Cancer Center @ Suffolk
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Rockville Centre
country: United States
facility: Memorial Sloan-Kettering at Mercy Medical Center
state: New York
city: Sleepy Hollow
country: United States
facility: Memoral Sloan Kettering Cancer Center at Phelps
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Helena Yu, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.