Trial Information

Phase II Study Of Single Agent Gefitinib (Iressa) In Patients With Clinical Stage I Non-Small Cell Lung Cancer (NSCLC) Proceeding To Mediastinoscopy And Surgery

Primary and Secondary Outcomes:

- Objectives:

- To assess the pathologic and radiological response rate after neoadjuvant
Gefitinib treatment

- To assess the toxicity of neoadjuvant Gefitinib treatment in clinical stage 1A &
1B NSCLC

- Enrollment

Treatment will be administered on an outpatient basis. Patients may be identified by
thoracic surgeons, respirologists and/or interventional chest radiologists for study
participation upon clinical and radiographic assessment.

**Diagnostic biopsy, Pretreatment Investigations

If patients have already had a core or FNA biopsy before referral, this material will be
sought from the original pathologist for review and inclusion in the study with appropriate
consent sought. If a patient does not have a biopsy upon presentation to the thoracic
surgeon, and consents to inclusion in the trial, baseline non-invasive assessment will be
carried out before a percutaneous biopsy will be mandated as part of entry into the study.
After non-invasive staging, patients will be subject to biopsy. In collaboration with
pathology, an immediate diagnosis will be made at the time of fine needle aspiration biopsy
(or bronchoscopy). After a pathologic diagnosis of cancer is confirmed, subjects will be
invited to have additional biopsies will be performed to obtain material for correlative
studies, assuming no complications or technical difficulties have arisen. These studies will
be done in collaboration with thoracic interventional radiologists from Diagnostic Imaging,
who supervises the lung fine needle aspirates and biopsies.

All patients will undergo pre-study assessments for symptoms, performance status,
radiographic assessment and blood tests (complete blood count, electrolytes, liver and renal
function tests). Assessment of response will occur after the 4-week treatment period.
Toxicity will be assessed continuously, with patient assessment weekly on treatment, repeat
blood tests at 2 weeks and imaging of measurable disease at 4 weeks. All subjects will be
invited to have their initial diagnostic biopsy and subsequent surgical tumor specimen
examined as part of the laboratory correlate component of the study. Patients will be
considered evaluable for pharmacodynamic assessment if they complete at least 21 of the
planned 28 days of therapy.

Once competed, oral Gefitinib will be administered at a dose of 250 mg (1 pill) daily for 28
days prior to the planned mediastinoscopy. Patients may take the pill either with or without
food, and are encouraged to take the medication at approximately the same time each day. If
the patient forgets to take a dose, they should take the last missed dose as soon as they
remember, as long as it is at least 12 hours before the next dose is due. If patient vomits
after taking the dose, the dose may be retaken if the tablet is seen in the emesis. The last
dose of Gefitinib will be administered not less than 48 hours prior to mediastinoscopy or
surgery.

If the mediastinoscopy reveals the presence of Stage III disease, the patient's
mediastinoscopy samples may still be analysed as part of the correlative study. Patients
will be followed for 90 days or as long as required after the last dose of Gefitinib to
ensure resolution of any Gefitinib-related toxicities. However these patients will be
offered standard therapy for stage III disease off of study protocol, for example a
combination of chemotherapy, radiation plus or minus surgical resection. If these patients
do proceed to thoracotomy post-chemotherapy and/or radiotherapy, their resection specimen
will not be eligible for this correlative protocol.

**Duration of Therapy and Follow-up

As outlined above, patients will be treated for 28 days before surgery and will also be
followed for 90 days post-operatively after thoracotomy to ensure the recovery from surgery.
Accrual is estimated at 2 patients per month, for 18 to 24 months, based on accrual rates to
other thoracic surgical studies at UHN. Study duration is planned from August 2004 to June
2006.

All patients will be followed in the current standard of care at University Health Network.
That is, clinic visits with chest x-ray every 3 months for 2 years, every 6 months in the
third year, and annually thereafter. Recorded information will only include vital status and
presence or absence of disease recurrence.