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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

Phase 2
18 Years
Not Enrolling

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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 &

- 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

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

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.

Inclusion Criteria:

- Patients must have biopsy-proven non-small cell lung carcinoma (NSCLC) or a lung
nodule seen on CT imaging and a high-clinical suspicion of NSCLC

- Clinical Stage 1A (T1N0M0 a tumor that is 3 cm or less in greatest dimension,
surrounded by lung or visceral pleura, and without bronchoscopic evidence of invasion
more proximal than the lobar bronchus (i.e., not in the main bronchus)

- or 1B (T2N0M0 a tumor with any of the following features of size or extent: More than
3 cm in greatest dimension. Involves the main bronchus, 2 cm or more distal to the
carina. Invades the visceral pleura. Associated with atelectasis or obstructive
pneumonitis that extends to the hilar region but does not involve the entire lung).

- Must be deemed appropriate surgical candidate

- ECOG performance status £ 2

- Age ³ 18 years

- No prior chemotherapy, radiotherapy or EGFR inhibitors

- Ability to understand and the willingness to sign a written informed consent

Exclusion Criteria:

- Patients who have received prior anticancer treatment with chemotherapy, radiotherapy
or EGFR inhibitor therapy;

- Patients who have had a previous diagnosis of cancer, are excluded except if have
been adequately treated for non-melanoma skin cancer or carcinoma in situ of the
cervix are eligible irrespective of when that treatment was given.

- Patients may not be receiving any other investigational or anticancer agents while on

- History of allergic reactions to Gefitinib or erlotinib

- Pre-existing diarrhea ³ NCI CTC Grade 2

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure or evidence of cardiac dysfunction,
unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease, poorly
controlled diabetes mellitus, clinically significant or untreated ophthalmologic
(e.g. Sjogrens etc.) or gastrointestinal conditions (e.g. Crohns disease, ulcerative
colitis) or psychiatric illness/social situations that would limit compliance with
study requirements.

- Pregnant women because of the unknown effects of Gefitinib on the human fetus.

- HIV-positive patients on active treatment

- Active malignancy at any other site including combined small cell and non-small cell
carcinomas or a pulmonary carcinoid tumor.

- Taking drugs that induce CYP3A4 enzymes, patients with ongoing use of phenytoin,
rifampicin, carbamazepine, barbiturates, rifampicin, or St John's Wort are excluded.

- Incomplete healing from previous surgery.

- Use of any agent that decreases gastric pH, including proton pump inhibitors,
Histamine-2 receptor blockers or sodium bicarbonate. Use of calcium or magnesium
based elixirs are not included.

Type of Study:


Study Design:

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

Outcome Measure:

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

Outcome Time Frame:

before starting drug and after 28 days of treatment

Safety Issue:


Principal Investigator

Thomas Waddell, MD FRCSC

Investigator Role:

Principal Investigator

Investigator Affiliation:

University Health Network, Toronto


Canada: Health Canada

Study ID:

UHN REB04-0420-C



Start Date:

January 2005

Completion Date:

November 2009

Related Keywords:

  • Lung Cancer
  • STAGE 1A & 1B
  • PHASE 2
  • Lung Neoplasms