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

Completed

• Conditions: Lung Cancer
• Interventions: Genetic: obtain tissue specimens

• Registration Number: NCT01300429
• Lead Sponsor: Memorial Sloan Kettering Cancer Center

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-02-08
• Study First Submitted: 2011-02-17
• Study First Submitted QC: 2011-02-18
• Study First Posted: 2011-02-21
• Status Verified: 2021-01
• Primary Completion: 2021-01-05
• Study Completion: 2021-01-05
• Last Update Submitted: 2021-01-06
• Last Update Posted: 2021-01-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• ≥18 years of age
• Histologically proven diagnosis of NSCLC at MSKCC Tumor positive for a translocation or inversion event involving the ALK gene locus
• Clinical response to treatment with crizotinib as defined by either:

Radiographic partial or complete response defined by RECIST or WHO

OR:

Radiographic stable disease for at least 8 weeks

• Radiographic progression of disease amenable to biopsy while on treatment with crizotinib as defined by RECIST or WHO
• Signed informed consent

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Exclusion Criteria

• Deemed by their treating physician to be medically unfit for biopsy
• Women who are pregnant or breast-feeding

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
patients with Non Small Cell Lung cancer	obtain tissue specimens	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.

Primary Outcome Measures

Name	Time	Method
the frequency of acquired mutations	2 years	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.

Trial Locations

Locations (1)

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States