Surgery for Early Lung Cancer With Preoperative Erlotinib (Tarceva): A Clinical Phase II Trial (SELECT)
Condition: Non Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Study type: Interventional
Phase: Phase 2

Summary: 
      2.5 Rationale for preoperative erlotinib therapy

      Erlotinib is the only EFGR tyrosine kinase inhibitor to demonstrate a survival advantage and
      symptom improvement in a large phase III trial after failure of chemotherapy in advanced
      non-small cell lung cancer (Shepherd, Rodrigues Pereira et al. 2005). Although the potential
      utility of erlotinib in earlier stage NSCLC is unclear, given its activity in advanced
      disease and its minimal toxicity profile, there is likely a subset of patients who may
      benefit and potentially be cured by adjuvant erlotinib therapy. Erlotinib may also have
      greater antitumour activity in earlier stage disease. Therefore, we propose a phase II study
      to assess erlotinib pre-operatively in clinical stage 1 and 2 NSCLC, and downstream effects
      on signal transduction pathways and possible markers of treatment resistance and sensitivity.

      The proposed study involves administering oral erlotinib for four weeks (28 days)
      preoperatively in early stage (1A/B, 2A/B) NSCLC. Current waiting times for surgical
      resection of early stage NSCLC at UHN ranges from 4 to 6 weeks (Hui, Johnston et al. 2004),
      thus patients would not experience significant delay in time to surgery through this trial
      design. This study provides the opportunity to explore the impact of erlotinib on early stage
      NSCLC in humans, with pharmacodynamic assessment expected in 100% of patients post-treatment,
      in addition to correlative imaging. This study will evaluate the feasibility of preoperative
      therapy with erlotinib, and may facilitate the identification of predictive markers for
      response to erlotinib in early stage NSCLC. This may help further define the subset of
      patients who would benefit from adjuvant EGFR tyrosine kinase inhibitors, and those who may
      require other adjuvant approaches including chemotherapy and further clinical trials.
    

Detailed description: 
      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.
    

Intervention name(s): Erlotinib; Erlotinib
Intervention type(s): Drug; Drug
Intervention description(s): 150mg once a day for 28 days; 28 days of Erlotinib before surgery in patients with stage I-IIb NSCLC
Other intervention name(s): Tarceva
Intervention MeSH terms: Erlotinib Hydrochloride
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Non Small Cell Lung Cancer; Lung Cancer; Erlotinib; Neoadjuvant Treatment