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

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

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.

Study Overview

• Status: Completed
• Conditions: Unresectable or Metastatic Non-small Cell Lung Cancer (NSCLC)
• Intervention / Treatment: 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 Type: Observational
• Enrollment (Actual): 228

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Basking Ridge, New Jersey, United States
      • Memoral Sloan Kettering Cancer Center
  • New York
    • Commack, New York, United States, 11725
      • Memorial Sloan-Kettering Cancer Center @ Suffolk
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • Rockville Centre, New York, United States
      • Memorial Sloan-Kettering at Mercy Medical Center
    • Sleepy Hollow, New York, United States, 10591
      • Memoral Sloan Kettering Cancer Center at Phelps

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

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

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To compare EGFR gene sequence in patients upon relapse with EGFR gene sequence prior to treatment with small molecule kinase inhibitors.	2 years

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center

Publications and helpful links

General Publications

• 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.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: August 1, 2004
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): February 1, 2016

Study Registration Dates

• First Submitted: December 20, 2007
• First Submitted That Met QC Criteria: December 20, 2007
• First Posted (Estimate): December 24, 2007

Study Record Updates

• Last Update Posted (Estimate): February 4, 2016
• Last Update Submitted That Met QC Criteria: February 3, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: NSCLC; non-small cell lung cancer; metastatic disease; resistent disease; RNA analysis; 04-103
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: 04-103