Gefitinib in Treating Patients With Stage IB, II, or IIIA Non-small Cell Lung Cancer That Was Completely Removed by Surgery

Inclusion Criteria:

• Patients must have histological proof of a primary non-small cell lung cancer (bronchoalveolar carcinomas presenting as a discrete solitary radiological mass ornodule are eligible)

• Patients must be classified post-operatively as stage IB, II or IIIA on the basis ofpathologic criteria

• At the time of resection a complete mediastinal lymph node resection or at least lymphnode sampling should have been attempted; if a complete mediastinal lymph noderesection or lymph node sampling was not undertaken, any mediastinal lymph node whichmeasured 1.5 cm or more on the pre-surgical computed tomography (CT)/magneticresonance imaging (MRI) scan or any area of increased uptake in the mediastinum on apre-surgical positron emission tomography (PET) scan must have been biopsied; note: apre-surgical PET scan is not mandatory

• The nodal tissue must be labelled according to the recommendations of theAmerican Thoracic Society; surgeons are encouraged to dissect or sample allaccessible nodal levels; the desirable levels for biopsy are:

• Right upper lobe: 4, 7, 10

• Right middle lobe: 4, 7, 10

• Right lower lobe: 4, 7, 9, 10

• Left upper lobe: 5, 6, 7, 10

• Left lower lobe: 7, 9, 10

• Surgery may consist of lobectomy, sleeve resection, bilobectomy or pneumonectomy asdetermined by the attending surgeon based on the intraoperative findings; patients whohave had only segmentectomies or wedge resections are not eligible for this study; allgross disease must have been removed at the end of surgery; all surgical margins ofresection must be negative for tumor

• No more than 16 weeks may have elapsed between surgery and randomization; for patientswho received post-operative adjuvant platinum-based chemotherapy, no more than 26weeks may have elapsed between surgery and randomization

• Patient must consent to provision of and investigator(s) must agree to submit arepresentative formalin fixed paraffin block of tumor tissue at the request of theCentral Tumor Bank in order that the specific EGFR correlative marker assays may beconducted

• The patient must have an Eastern Cooperative Oncology Group (ECOG) performance statusof 0, 1 or 2

• Leukocytes >= 3.0 x 10^9/L or >= 3000/ul

• Absolute granulocyte count >= 1.5 x 10^9/L or >= 1,500/ul

• Platelets >= 100 x 10^9/L or >= 100,000/ul

• Total bilirubin within normal institutional limits

• Alkaline phosphatase =< 2.5 x institutional upper limit of normal; if alkalinephosphatase is greater than the institutional upper limit of normal (UNL) but lessthan the maximum allowed, an abdominal (including liver) ultrasound, CT or MRI scanand a radionuclide bone scan must be performed prior to randomization to rule outmetastatic disease; if the values are greater than the maximum allowed, patients willnot be considered eligible regardless of findings on any supplementary imaging

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])and/or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal; if AST (SGOT) or ALT (SGPT) are greaterthan the institutional upper limit of normal (UNL) but less than the maximum allowed,an abdominal (including liver) ultrasound, CT or MRI scan must be performed prior torandomization to rule out metastatic disease; if the values are greater than themaximum allowed, patients will not be considered eligible regardless of findings onany supplementary imaging

• Patient must have a chest x-ray done within 14 days prior to randomization; patientmust have a CT or MRI scan of the chest done within 90 days prior to surgicalresection if at least one of the following was undertaken:

• A complete mediastinal lymph node resection; or

• Biopsy of all desired levels of lymph nodes - as specified above; or

• A pre-surgical PET scan within 60 days prior to surgical resection If none of theabove was undertaken then the CT or MRI scan of the chest must have beenperformed within 60 days prior to surgical resection Note: a pre-surgical PETscan is not mandatory

• Patient must have an electrocardiogram (EKG) done within 14 days prior torandomization

• Women of childbearing age and men must agree to use adequate contraception (hormonalor barrier method of birth control) prior to study entry and while taking studymedication and for a period of three months after final dose; should a woman becomepregnant or suspect she is pregnant while she or her male partner are participating inthis study, she should inform her treating physician immediately

• Patients may receive post-operative radiation therapy; patients must have completedradiation at least 3 weeks prior to randomization and have recovered from allradiation-induced toxicity; patients who have received radiation therapy should alsobe randomized within 16 weeks of surgery

• Patient consent must be obtained according to local institutional and/or UniversityHuman Experimentation Committee requirements; it will be the responsibility of thelocal participating investigators to obtain the necessary local clearance, and toindicate in writing to either the National Cancer Institute of Canada (NCIC) ClinicalTrials Group (CTG) study coordinator (for NCIC CTG centers) or the Cancer TrialsSupport Unit (CTSU) (for all other investigators), that such clearance has beenobtained, before the trial can commence in that center; a standard consent form forthe trial will not be provided, but a sample form is given; this sample consent formhas been approved by the National Cancer Institute (NCI) Central Institutional ReviewBoard (IRB) and must be used unaltered by those CTSI centers which operate under CIRBauthority; for NCIC CTG centers, a copy of the initial full board Research EthicsBoard (REB) approval and approved consent form must be sent to the NCIC CTG centraloffice; please note that the consent form for this study must contain a statementwhich gives permission for the government agencies, NCI, NCIC CTG and monitoringagencies to review patient records

• NCIC-CTG Centers: the patient must have the ability to understand and thewillingness to sign a written informed consent document; the patient must signthe consent form prior to randomization

• CTSU Centers: the patient, or in the case of a mentally incompetent patient hisor her legally authorized and qualified representative, must have the ability tounderstand and the willingness to sign a written informed consent document; theconsent form must be signed prior to randomization

• Patients must be accessible for treatment and follow-up; investigators must assurethemselves that patients registered on this trial will be available for completedocumentation of the treatment administered, toxicity and follow-up

• Initiation of protocol treatment must begin within 10 working days of patientrandomization

• Patients may have received post-operative adjuvant platinum-based chemotherapy;patients must have completed chemotherapy at least 3 weeks prior to randomization andhave recovered from all chemotherapy-induced toxicity; patients who have receivedadjuvant chemotherapy should also be randomized within 26 weeks of surgery

Exclusion Criteria:

• Prior or concurrent malignancies; patients who have had a previous diagnosis ofcancer, if they remain free of recurrence and metastases five years or more followingthe end of treatment and, in the opinion of the treating physician do not have asubstantial risk of recurrence of the prior malignancy, are eligible for the study;patients who have been adequately treated for non-melanomatous skin cancer orcarcinoma in situ of the cervix are eligible irrespective of when that treatment wasgiven

• A combination of small cell and non-small cell carcinomas or a pulmonary carcinoidtumor

• More than one discrete area of apparent primary cancer (even if within the same lobe,T4, IIIB)

• Clinically significant or untreated ophthalmologic (e.g. Sjogren's etc.) orgastrointestinal conditions (e.g. Crohn's disease, ulcerative colitis)

• Any active pathological condition that would render the protocol treatment dangeroussuch as: uncontrolled congestive heart failure, angina, or arrhythmias, activeuncontrolled infection, or others

• A history of psychiatric or neurological disorder that would make the obtainment ofinformed consent problematic or that would limit compliance with study requirements

• Patient, if female, is pregnant or breast-feeding

• Neoadjuvant chemotherapy or immunotherapy for NSCLC; however, patients may havereceived pre-operative limited field, low dose (less than 1000 cGy) external beamradiation therapy or endobronchial brachytherapy or laser therapy for short termcontrol of hemoptysis or lobar obstruction; full dose pre-operative radiotherapy ofcurative intent is a cause for exclusion; patients may have received post-operativeadjuvant platinum-based chemotherapy however non-platinum-based chemotherapy is acause for exclusion

• History of allergic reactions attributed to compounds of similar chemical or biologiccomposition to the agents used on this trial; patients with ongoing use of phenytoin,carbamazepine, barbiturates, rifampicin, or St John's Wort are excluded

• Incomplete healing from previous oncologic or other major surgery