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

Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01300429
• Other study ID #: 11-014
• Status: Completed
• Start date: February 8, 2011
• Est. completion date: January 5, 2021

Study information

• Verified date: January 2021
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: January 5, 2021
• Est. primary completion date: January 5, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms

Intervention

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.

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Cancer Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	the frequency of acquired mutations	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.	2 years

External Links

•   Memorial Sloan Kettering Cancer Center