Registry for Patients With Acquired Resistance to Small Molecule Kinase Inhibitors in Non-Small-Cell Lung Cancer
This study has been completed.
Sponsor:
Memorial Sloan Kettering Cancer Center
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00579683
First received: December 20, 2007
Last updated: February 3, 2016
Last verified: February 2016
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Purpose
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 | Intervention |
|---|---|
|
Unresectable or Metastatic Non-small Cell Lung Cancer (NSCLC) |
Other: Tumor core biopsy for RNA isolation |
| Study Type: | Observational |
| Study Design: | 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 |
Resource links provided by NLM:
Genetics Home Reference related topics:
lung cancer
Drug Information available for:
Ribonucleic acid
U.S. FDA Resources
Further study details as provided by Memorial Sloan Kettering Cancer Center:
Primary Outcome Measures:
- 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 ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- 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 ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- To identify novel mechanisms of acquired resistance to EGFR small molecule kinase inhibitors. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
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.
| Enrollment: | 228 |
| Study Start Date: | August 2004 |
| Study Completion Date: | February 2016 |
| Primary Completion Date: | February 2016 (Final data collection date for primary outcome measure) |
| Groups/Cohorts | Assigned Interventions |
|---|---|
|
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.
|
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.
Eligibility| Ages Eligible for Study: | Child, Adult, Senior |
| Genders Eligible for Study: | Both |
| 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:
Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00579683
Please refer to this study by its ClinicalTrials.gov identifier: NCT00579683
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:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Memorial Sloan Kettering Cancer Center |
| ClinicalTrials.gov Identifier: | NCT00579683 History of Changes |
| Other Study ID Numbers: | 04-103 |
| Study First Received: | December 20, 2007 |
| Last Updated: | February 3, 2016 |
| Health Authority: | United States: Food and Drug Administration |
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 |
ClinicalTrials.gov processed this record on September 29, 2016