Phase II Trial to Correlate Radiographic Response Induced By Gefitinib With Mutations in the Protein-Tyrosine Kinase Domain of the EGF Receptor Gene - Full Text View

Sponsored by:	Memorial Sloan-Kettering Cancer Center
Information provided by:	Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT00588445

Purpose

The purpose of this research study is to:

see if gefitinib pills can shrink Stage 1 or 2 non-small cell lung cancers before surgery
see if your non-small cell lung cancer has a mutation in a certain part of the EGFR gene
see if patients whose tumor does shrink with gefitinib treatment are more likely to have a mutation in a certain part of the EGFR gene
see if the pattern of protein expression in the blood is related to the tumor's sensitivity or resistance to gefitinib treatment.
see if expression of certain genes in the tumor are related to the tumor's sensitivity or resistance to gefitinib treatment.

Condition	Intervention	Phase
Lung Cancer Non-Small Cell Lung Cancer Bronchioloalveolar Cancer	Drug: Gefitinib	Phase II

MedlinePlus related topics: Cancer Lung Cancer Surgery

Drug Information available for: Tyrosine ZD1839

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title:	Phase II Trial to Correlate Radiographic Response Induced By Gefitinib With Mutations in the Protein-Tyrosine Kinase Domain of the EGF Receptor Gene in Patients With NSCLC

Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:

To correlate the radiographic response to gefitinib with the presence of mutations in the protein-tyrosine kinase domain of the EGF receptor gene in tumor specimens obtained before treatment with gefitinib. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Microarray analysis to identify gene(s) or gene clusters that exhibit changes in gene expression; Time to relapse and overall survival data [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	50
Study Start Date:	June 2004
Estimated Study Completion Date:	June 2010
Estimated Primary Completion Date:	June 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Treatment: Experimental	Drug: Gefitinib Patients will receive gefitinib 250 mg po daily for at least 21 days preoperatively (depending on the timing of the surgery). Treatment with gefitinib will be stopped 2 days before the date of surgery. Patients who have had at least a minor response to gefitinib therapy preoperatively (> 25% reduction in tumor measured bidimensionally) and / or have mutations in the protein-tyrosine kinase domain of the EGF receptor gene identified will continue on the study and will resume gefitinib treatment after at least 7 days from surgery providing adequate wound healing has occurred. Patients who are determined to be candidates for adjuvant chemotherapy and/or radiation therapy by their treating physician may receive treatment with adjuvant chemotherapy and/or radiation therapy. The post-operative gefitinib will be started after completion of the chemotherapy and/or radiation therapy.

Arms

Assigned Interventions

Treatment: Experimental

Drug: Gefitinib

Patients will receive gefitinib 250 mg po daily for at least 21 days preoperatively (depending on the timing of the surgery). Treatment with gefitinib will be stopped 2 days before the date of surgery. Patients who have had at least a minor response to gefitinib therapy preoperatively (> 25% reduction in tumor measured bidimensionally) and / or have mutations in the protein-tyrosine kinase domain of the EGF receptor gene identified will continue on the study and will resume gefitinib treatment after at least 7 days from surgery providing adequate wound healing has occurred. Patients who are determined to be candidates for adjuvant chemotherapy and/or radiation therapy by their treating physician may receive treatment with adjuvant chemotherapy and/or radiation therapy. The post-operative gefitinib will be started after completion of the chemotherapy and/or radiation therapy.

Detailed Description:

This is a phase II, single institution trial to correlate gefitinib response and mutations in the protein-tyrosine kinase domain of the EGF receptor gene. The study will be conducted in patients with Stage I and II NSCLC who have been determined to be operable and resectable.

Patients must have 1 or more of the following features: never smoker or smoking history of < 15 pack years and/or features of bronchioloalveolar lung cancer. 50 patients will be enrolled on this study. Treatment will be with gefitinib for at least 21 days before surgery (depending on the timing of the surgery). Patients will discontinue gefitinib 2 days before their operation. For patients that demonstrate a radiographic response to gefitinib preoperatively and /or patients with mutations in the protein-tyrosine kinase domain of the EGF receptor gene (identified from the surgical sample), gefitinib will continue for 2 years post-surgery. Patients who do not have evidence of radiographic response or mutations in the protein-tyrosine kinase domain of the EGF receptor gene will be removed from the study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Pathologic confirmation of malignancy at Memorial Sloan-Kettering
Patients must have previously untreated stage I or II NSCLC (T11-2N0M0, T1-2N1M0, T3N0M0) and 1 of the following features: never smoker or < 15 pack year smoking history and/or bronchioloalveolar cancer (either pure BAC, BAC with focal invasion or adenocarcinoma with BAC features)
Patients must have been determined to be operable and resectable by the treating thoracic surgeon.
Age >18 years.
Measurable indicator lesions
Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

Pregnant or lactating women or women of childbearing potential not using effective contraception. Men participating in the trial must also use effective contraception when sexually active.
Patients may not be receiving any other investigational agents.
Any history of or evidence of interstitial lung disease (patients with chronic stable radiographic changes who are asymptomatic need not be excluded).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00588445

Contacts

Contact: Naiyer Rizvi, MD

rizvin@mskcc.org

Locations

United States, New York
Memorial Sloan-Kettering Cancer Center	Recruiting
New York, New York, United States, 10065
Contact: Naiyer Rizvi, Md rizvin@mskcc.org

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

Investigators

Principal Investigator:

Naiyer Rizvi, MD

Memorial Sloan-Kettering Cancer Center

More Information

Additional Information:

Memorial Sloan-Kettering web site This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Memorial Sloan-Kettering Cancer Center ( Naiyer Rizvi, MD )
Study ID Numbers:	04-071, CA113653
Study First Received:	December 26, 2007
Last Updated:	December 9, 2008
ClinicalTrials.gov Identifier:	NCT00588445 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:

Lung Cancer
Non-small cell lung cancer
Gefitnib
Cancer

NSCLC
bronchioloalveolar cancer
smoker

Study placed in the following topic categories:

Thoracic Neoplasms
Respiratory Tract Diseases
Lung Neoplasms
Lung Diseases
Adjuvants, Immunologic
Non-small Cell Lung Cancer

Protein Kinase Inhibitors
Gefitinib
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial
Carcinoma

Additional relevant MeSH terms:

Thoracic Neoplasms
Respiratory Tract Neoplasms
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors
Protein Kinase Inhibitors
Pharmacologic Actions
Carcinoma

Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Lung Neoplasms
Therapeutic Uses
Lung Diseases
Carcinoma, Non-Small-Cell Lung
Gefitinib
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on May 07, 2009