Surgery for Early Lung Cancer With Preoperative Erlotinib (Tarceva): A Clinical Phase II Trial
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.
4.2 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, a percutaneous biopsy will be mandated as
part of entry into the study. The order of test will be up to the treating thoracic surgeon.
As part of this procedure a large localizing needle is inserted into the tumour. In
collaboration with pathology, a fine needle is passed through the outer needle and an
immediate diagnosis will be made at the time of fine needle aspiration biopsy. After a
pathologic diagnosis of cancer is confirmed, additional biopsies to obtain material for
correlative studies will be performed through the standard localizing needle, assuming no
complications or technical difficulties have arisen. These studies will be done in
collaboration with thoracic interventional radiologists from Diagnostic Imaging, who perform
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). Blood samples before treatment and post treatment with erlotinib will be
banked for future serum proteomic analysis. 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.
Patients will have PET-CT scan study done pre- and post-treatment (see section 7). If the
enrolment PET-CT imaging reveals mediastinal disease (IIIA or IIIB) or extensive disease and
this is pathologically confirmed the patient will not be enrolled in the study.
Once the diagnosis is established and assessment completed, oral erlotinib will be
administered at a dose of 150 mg (1 pill) daily for 28 days prior to the planned
mediastinoscopy and/or surgery. Tablets should be taken preferably in the morning with up to
200 mL of water at least 1 hour before or 2 hours after meals. 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 erlotinib will
be administered early in the morning of the mediastinoscopy or surgery.
If the mediastinoscopy reveals the presence of Stage III disease, the patient's
mediastinoscopy samples may still be analyzed as part of the correlative study. Patients
will be followed for 90 days or as long as required after the last dose of erlotinib to
ensure resolution of any erlotinib-related toxicities. However these patients will be
offered standard therapy for stage III disease off study protocol, for example a combination
of chemotherapy, radiation with or without 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.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
changes in tumor cell proliferation measured by a 75% reduction of Ki67 Immunohistochemistry (ICH) expression comparing pre and postoperative lung cancer
Before surgery and after surgery
Natasha Leighl, MD FRCPC
University Health Network, Toronto
Canada: Health Canada
UHN REB#: 06-0052-C