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

NCT01300429 | Completed

• 1 other identifier: 11-014
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Lung Cancer

Keywords

core biopsy; Resistance to Crizotinib; Non-small Cell Lung Cancer; 11-014

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (1)

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

Interventions

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.

patients with Non Small Cell Lung cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All patients seen by the Thoracic Oncology Service who have been diagnosed with an ALK mutant NSCLC and treated with an ALK kinase inhibitor who have experienced objective regression by RECIST, WHO, or clinical criteria and who then progress will be screened for this protocol.

You may qualify if:

• ≥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

You may not qualify if:

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

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

Biospecimen

Retention: SAMPLES WITH DNA

Tissue

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Study Officials

• Gregory Riely, MD, PhD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2011
• First Posted: February 21, 2011
• Study Start: February 8, 2011
• Primary Completion: January 5, 2021
• Study Completion: January 5, 2021
• Last Updated: January 7, 2021

Record last verified: 2021-01

Locations

US (1)