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

• ClinicalTrials.gov Identifier: NCT00579683
• Recruitment Status: Completed
• First Posted: December 24, 2007
• Last Update Posted: February 4, 2016
• Sponsor: Memorial Sloan Kettering Cancer Center
• Information provided by (Responsible Party): Memorial Sloan Kettering Cancer Center

Study Description

Brief 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.

Condition or disease	Intervention/treatment
Unresectable or Metastatic Non-small Cell Lung Cancer (NSCLC)	Other: Tumor core biopsy for RNA isolation

Detailed 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.

Study Design

• Study Type: Observational
• Actual Enrollment: 228 participants
• Observational Model: Case-Only
• Time Perspective: Prospective
• Official Title: A Prospective Registry for Patients With Acquired Resistance to Small Molecule Kinase Inhibitors in Non-Small-Cell Lung Cancer
• Study Start Date: August 2004
• Actual Primary Completion Date: February 2016
• Actual Study Completion Date: February 2016

Groups and Cohorts

Group/Cohort	Intervention/treatment
1; This is a protocol to study tissue specimens to identify changes in tumor DNA in NSCLC patients who have previously responded to therapy and who have subsequently experienced disease progression.	Other: Tumor core biopsy for RNA isolation; RNA isolation will be carried out using approximately 25 mg of gross tissue from these tumor specimens.

Outcome Measures

Primary Outcome Measures :

1. To compare EGFR gene sequence in patients upon relapse with EGFR gene sequence prior to treatment with small molecule kinase inhibitors. [ Time Frame: 2 years ]

Secondary Outcome Measures :

1. To identify novel mutations in the tyrosine kinase domain of EGFR in patients with acquired resistance to small molecule kinase inhibitors. [ Time Frame: 2 years ]
2. To more precisely characterize the frequency and clinical implications of T790M in patients with acquired resistance to small molecule kinase inhibitors. [ Time Frame: 2 years ]
3. To identify novel mechanisms of acquired resistance to EGFR small molecule kinase inhibitors. [ Time Frame: 2 years ]

Biospecimen Retention:   Samples With DNA

Tumor biopsy material will be processed to obtain RNA for analysis of EGFR sequence. Sequencing of additional candidate genes and other studies will follow if sufficient material is available.

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Unresectable or metastatic non-small cell lung cancer (NSCLC)

Criteria

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:

• None

Contacts and Locations

Locations

United States, New Jersey

Memoral Sloan Kettering Cancer Center

Basking Ridge, New Jersey, United States

United States, New York

Memorial Sloan-Kettering Cancer Center @ Suffolk

Commack, New York, United States, 11725

Memorial Sloan Kettering Cancer Center

New York, New York, United States, 10065

Memorial Sloan-Kettering at Mercy Medical Center

Rockville Centre, New York, United States

Memoral Sloan Kettering Cancer Center at Phelps

Sleepy Hollow, New York, United States, 10591

Sponsors and Collaborators

Memorial Sloan Kettering Cancer Center

Investigators

• Principal Investigator: Helena Yu, MD; Memorial Sloan Kettering Cancer Center

More Information

Additional Information:

Related Info 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Oxnard GR, Arcila ME, Sima CS, Riely GJ, Chmielecki J, Kris MG, Pao W, Ladanyi M, Miller VA. Acquired resistance to EGFR tyrosine kinase inhibitors in EGFR-mutant lung cancer: distinct natural history of patients with tumors harboring the T790M mutation. Clin Cancer Res. 2011 Mar 15;17(6):1616-22. doi: 10.1158/1078-0432.CCR-10-2692. Epub 2010 Dec 6.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT00579683
• Other Study ID Numbers: 04-103
• First Posted: December 24, 2007
• Last Update Posted: February 4, 2016
• Last Verified: February 2016

Keywords provided by Memorial Sloan Kettering Cancer Center:

non-small cell lung cancer; NSCLC; metastatic disease; resistent disease; RNA analysis; 04-103

Additional relevant MeSH terms:

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