Molecular Determinants of Acquired Clinical Resistance to Crizotinib in Non-small Cell Lung Cancer Harboring a Translocation or Inversion Event Involving the ALK Gene Locus
The purpose of this study is to try to learn more about how small molecule kinase inhibitor medications work in treating lung cancer. Crizotinib (PF-02341066) is a drug that has been shown to shrink tumors in some patients with lung cancer. While the investigators know how this drug works to stop the growth of tumors that depend on change in the gene named ALK (also called EML4-ALK), the investigators do not know why the drug stops working. The investigators would like to examine the tumor to help us better understand why crizotinib has stopped working as well as it once did. The tumor will be examined with multiple tests to look for the reason that crizotinib stopped working.
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||Molecular Determinants of Acquired Clinical Resistance to Crizotinib in Non-small Cell Lung Cancer Harboring a Translocation or Inversion Event Involving the ALK Gene Locus|
- the frequency of acquired mutations [ Time Frame: 2 years ] [ Designated as safety issue: No ]ALK sequence from tumor tissue pre-treatment in patients that respond to crizotinib will be compared to ALK sequence in tumor tissue after the development of resistance when there is persistence of the original ALK inversion or translocation event.
Biospecimen Retention: Samples With DNA
|Study Start Date:||February 2011|
|Estimated Study Completion Date:||February 2015|
|Estimated Primary Completion Date:||February 2015 (Final data collection date for primary outcome measure)|
patients with Non Small Cell Lung cancer
This is a protocol to obtain and/or analyze tissue specimens of patients with NSCLC harboring an activating ALK inversion or translocation that have had a previous clinical response to tyrosine kinase inhibitor therapy and subsequently experience progressive disease. The tissue will be used to identify changes in the ALK gene that are acquired during treatment with an ALK TKI and may account for acquired resistance.
Genetic: obtain tissue specimens
One core biopsy specimen will be placed in formalin and processed for cytogenetic and FISH analyses as well as DNA for ALK sequencing. The second core biopsy specimen will be immediately frozen in liquid nitrogen and stored in a -80 degree freezer for research specimen. Collection will be performed on-site at the time of the procedure.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01300429
|United States, New York|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10065|
|Principal Investigator:||Gregory Riely, MD, PhD||Memorial Sloan-Kettering Cancer Center|