Registry for Patients With Acquired Resistance to Small Molecule Kinase Inhibitors in Non-Small-Cell Lung Cancer

Unresectable or Metastatic Non-small Cell Lung Cancer (NSCLC) Clinical Trial

Official title:

A Prospective Registry for Patients With Acquired Resistance to Small Molecule Kinase Inhibitors in Non-Small-Cell Lung Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00579683
• Other study ID #: 04-103
• Status: Completed
• Phase: N/A
• First received: December 20, 2007
• Last updated: February 3, 2016
• Start date: August 2004
• Est. completion date: February 2016

Study information

• Verified date: February 2016
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to try to learn more about how small molecule kinase inhibitors work in treating lung cancer. Some early studies have shown that gefitinib, erlotinib and similar drugs are more likely to work if a particular DNA change (also known as a mutation) is found in a protein that is important in lung cancer. This protein is called the epidermal growth factor receptor (EGFR). Since small molecule kinase inhibitors sometimes stop working, we would like to examine your tumor to learn why these medicines are not working as well. Your tumor will be examined for a variety of things including changes in the DNA of the EGFR. We will also sequence parts of the genes for HER2, HER3, HER4, and KRAS, other proteins thought to be important in lung cancer.

Description:

The goal of this protocol is to determine mechanisms of resistance to epidermal growth factor (EGFR) tyrosine kinase inhibitors (EGFR-TKI) in non-small cell lung cancer (NSCLC). A number of trials have shown small molecule kinase inhibitors to be active agents in the treatment of NSCLC [1]. Clinically these drugs have been noted to produce dramatic but infrequent responses. Mutations in the epidermal growth factor receptor have been shown to correlate with sensitivity to gefitinib and erlotinib[2,3]. However, we know that most patients who have initial responses to EGFR-TKI eventually progress. The mechanism of acquired clinical resistance to these inhibitors in patients incompletely understood.

This is a protocol to study clinical characteristics and biopsy tissue of patients with non-small cell lung cancer who have had previous clinical response to small molecule kinase inhibitors and subsequently experience progression of disease. The tissues and other specimens will be used to carry out laboratory studies to explore the molecular basis of sensitivity and resistance to small molecule kinase inhibitors.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 228
• Est. completion date: February 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria:

Patients diagnosed with unresectable or metastatic non-small cell lung cancer (NSCLC) and who fulfill the following eligibility criteria will be considered eligible for this study.

• Patient must have previously received treatment with small molecule kinase inhibitors targeting at least, in part, EGFR patients may have received other treatments since treatment with small molecule kinase inhibitors including radiation or chemotherapy)

• Development of disease progression while actively receiving tyrosine kinase inhibitor

• Signed informed consent

Exclusion Criteria:

Study Design

Observational Model: Case-Only, Time Perspective: Prospective

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Unresectable or Metastatic Non-small Cell Lung Cancer (NSCLC)

Intervention

Other:
• Tumor core biopsy for RNA isolation
RNA isolation will be carried out using approximately 25 mg of gross tissue from these tumor specimens.

Locations

Country	Name	City	State
United States	Memoral Sloan Kettering Cancer Center	Basking Ridge	New Jersey
United States	Memorial Sloan-Kettering Cancer Center @ Suffolk	Commack	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Memorial Sloan-Kettering at Mercy Medical Center	Rockville Centre	New York
United States	Memoral Sloan Kettering Cancer Center at Phelps	Sleepy Hollow	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	To compare EGFR gene sequence in patients upon relapse with EGFR gene sequence prior to treatment with small molecule kinase inhibitors.		2 years	No
Secondary	To identify novel mutations in the tyrosine kinase domain of EGFR in patients with acquired resistance to small molecule kinase inhibitors.		2 years	No
Secondary	To more precisely characterize the frequency and clinical implications of T790M in patients with acquired resistance to small molecule kinase inhibitors.		2 years	No
Secondary	To identify novel mechanisms of acquired resistance to EGFR small molecule kinase inhibitors.		2 years	No

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