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.

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Key information

Conditions

Lung Cancer Bronchial Neoplasms Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Lung Diseases Lung Neoplasms Neoplasms Neoplasms by Site Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Memorial Sloan Kettering Cancer Center

New York, 10065, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Exclusion criteria

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

Treatment and study plan

obtain tissue specimens

Genetic

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.

Primary outcomes

the frequency of acquired mutations

Time frame: 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.

Sponsors and collaborators

Lead sponsor

Memorial Sloan Kettering Cancer Center

Other

Registry information

Important dates

Study start: 2011
Primary completion: 2021
Study completion: 2021
First posted: Feb 21, 2011
Registry last updated: Jan 7, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed