Clinical trial NCT00588445: Phase II Trial to Correlate Radiographic Response Induced By Gefitinib With Mutations in the Protein-Tyrosine Kinase Domain of the EGF Receptor Gene
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Cancer
Non-small Cell Lung Cancer
Bronchioloalveolar Cancer
Keywords: Lung Cancer
Non-small cell lung cancer
Gefitnib
Cancer
NSCLC
bronchioloalveolar cancer
smoker
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
First posted: 2008-01-08
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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 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).

Primary outcomes:
measure: The Radiographic Response to Gefitinib
timeFrame: 21 days
Secondary outcomes:
measure: Microarray Analysis to Identify Gene(s) or Gene Clusters That Exhibit Changes in Gene Expression; Time to Relapse and Overall Survival Data
timeFrame: 2 years
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Naiyer Rizvi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.