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

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

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.

Study Overview

• Status: Completed
• Conditions: Lung Cancer; Non-small Cell Lung Cancer; Bronchioloalveolar Cancer
• Intervention / Treatment: Drug: Gefitinib

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.

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center

Publications and helpful links

General Publications

• Dercle L, Fronheiser M, Lu L, Du S, Hayes W, Leung DK, Roy A, Wilkerson J, Guo P, Fojo AT, Schwartz LH, Zhao B. Identification of Non-Small Cell Lung Cancer Sensitive to Systemic Cancer Therapies Using Radiomics. Clin Cancer Res. 2020 May 1;26(9):2151-2162. doi: 10.1158/1078-0432.CCR-19-2942. Epub 2020 Mar 20.
• Zhao B, Oxnard GR, Moskowitz CS, Kris MG, Pao W, Guo P, Rusch VM, Ladanyi M, Rizvi NA, Schwartz LH. A pilot study of volume measurement as a method of tumor response evaluation to aid biomarker development. Clin Cancer Res. 2010 Sep 15;16(18):4647-53. doi: 10.1158/1078-0432.CCR-10-0125. Epub 2010 Jun 9.

Helpful Links

• Memorial Sloan-Kettering web site

Study record dates

Study Major Dates

• Study Start: June 1, 2004
• Primary Completion (Actual): September 1, 2010
• Study Completion (Actual): September 1, 2010

Study Registration Dates

• First Submitted: December 26, 2007
• First Submitted That Met QC Criteria: January 7, 2008
• First Posted (Estimate): January 8, 2008

Study Record Updates

• Last Update Posted (Estimate): January 22, 2016
• Last Update Submitted That Met QC Criteria: December 17, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: Cancer; Lung Cancer; NSCLC; Non-small cell lung cancer; smoker; Gefitnib; bronchioloalveolar cancer
• 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; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Gefitinib
• Other Study ID Numbers: 04-071; CA113653