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

Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00588445
• Other study ID #: 04-071
• Secondary ID: CA113653
• Status: Completed
• Phase: Phase 2
• First received: December 26, 2007
• Last updated: December 17, 2015
• Start date: June 2004
• Est. completion date: September 2010

Study information

• Verified date: December 2015
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 65
• Est. completion date: September 2010
• Est. primary completion date: September 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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).

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bronchioloalveolar Cancer
• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

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.

Locations

Country	Name	City	State
United States	Memorial Sloan-Kettering Cancer Center	New York	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	The Radiographic Response to Gefitinib	Radiographic response is defined as a minor response ( > 25% decrease in the sum of the products of measured lesions)	21 days	No
Secondary	Microarray Analysis to Identify Gene(s) or Gene Clusters That Exhibit Changes in Gene Expression; Time to Relapse and Overall Survival Data	Each patient provides two binary variables: presence/absence of mutation and responder/non responder. The association between the two will be tested using the Fisher's exact test for the resulting 2x2 table.Changes in expression levels within a patient will be assessed using a paired t-test. Similarly differences in expression levels between responders and non-responders will be assessed using a two-sample t-test. Appropriate adjustment will be made for the multiple comparisons problem that arises because there are over 21,000 probe sets on the U133A array.	2 years	Yes

External Links

•   Memorial Sloan-Kettering web site