This phase II trial is studying how well erlotinib works in treating patients with stage I,
stage II, or stage IIIA non-small cell lung cancer. Erlotinib may stop the growth of tumor
cells by blocking the enzymes necessary for their growth. Giving erlotinib before surgery
may shrink the tumor so that it can be removed.
I. To determine the biochemical response rate (> 75% decrease in P-MAPK and/or P-AKT) with
daily oral OSI-774 (erlotinib) for 14 consecutive days in patients with early stage,
I. To evaluate the safety and tolerance of daily oral OSI-774 (erlotinib) as pre-operative
treatment for early stage operable NSCLC.
I. To correlate antiproliferative (Ki-67, p27) and apoptotic (TUNEL assay) tumor responses
to OSI-774 (erlotinib) with pre-therapy tumor and skin EGFR pathway functional status and
post-therapy tumor and skin EGFR pathway inhibition in patients with resectable NSCLC
treated preoperatively with OSI-774 (erlotinib) for 14 days.
II. Assessment of functional EGFR status: HER1, HER-2, HER3, HER4, PHER1, AKT, P-AKT,
MAPK-P-MAPK, STAT-3, P-STAT-3, EGFR-III by immunohistochemistry (IHC).
III. Assessment of proliferative response: Ki67 and p27 by IHC. IV. Assessment of apoptotic
response: TUNEL assay. V. To study the role of the gastrin-releasing factor and estrogen
receptor pathways in the sensitivity and resistance of NSCLC to OSI-774 (erlotinib).
VI. To identify patterns of gene and protein expression pre-therapy and post-therapy that
are associated with tumor clinical, biochemical, antiproliferative, and apoptotic responses.
VII. To study the antitumor activity of OSI-774 (erlotinib) in NSCLC tumors
heterotransplanted in nude mice after surgical resection and to investigate the sequential
molecular changes associated with tumor response to OSI-774 (erlotinib) therapy.
OUTLINE: This is a multicenter study.
Patients receive oral erlotinib once daily on days 1-14 or days 1-21 in the absence of
unacceptable toxicity. Patients then undergo surgical resection on the last day of study
drug administration (day 14 or day 21). Patients may receive chemotherapy and/or
radiotherapy after surgical resection at the discretion of the primary physician.
Patients are followed for 5 years after study registration.
- Patients with suspicion of lung cancer without distant metastases
- Patients are scheduled to have a tissue diagnostic procedure within 3 to 5 days of
- Patients are willing to allow collection and submission of baseline and post-therapy
tumor tissue, skin and blood samples for this study
- Patients must have ECOG performance status of 0, 1, or 2
- Patients must have no psychological, familial, sociological, or geographic conditions
that will interfere with medical follow-up and compliance with the study protocol
- Patients must have no prior chemotherapy or radiation therapy or no prior anti- EGFR
- Patients must be able to take oral medication and not have malabsorption syndrome, or
prior gastrointestinal surgery that limits their absorption (i.e. requiring total
- Patients must not be using phenytoin, carbamazepine, barbiturates, rifampicin,
phenobarbital, oxcarbazepine, rifapentine, St John's Wort, or any other CYP 3A4
enzyme-inducing agent; any use of these substances must be discontinued at least 2
weeks prior to registration
- Patients must not be taking any anti-coagulants
- Patients must not have been treated with a non-approved or investigational drug
within 21 days prior to pre-registration; patients must not have serious underlying
medical condition that would impair the ability of patient to receive the planned
- Patients with a known hypersensitivity to OSI-774 (erlotinib) are not eligible
- Patients must have histologically confirmed NSCLC; cytologic specimens obtained by
brushing, washing or needle aspiration of defined lesions will be acceptable
- Patients must have stage IA (T1N0M0), stage IB (T2N0M0), stage IIA (T1N1M0), stage
IIB (T2N1M0; T3N0-1M0), or stage IIIA (T1-3N2M0) disease
- Patients with small cell component on histology specimen are not eligible
- A paraffin-embedded cell block and 1-2 segments of frozen tissue demonstrating NSCLC
and obtained during the diagnostic biopsy is available for submission
- Patients must be considered operable candidates and disease must be considered
- Pregnant or breastfeeding women are excluded from the study because the agents used
in this study may be teratogenic to a fetus or child and there is no information on
the excretion of the agents or their metabolites into breast milk
- All females of childbearing potential must have a blood test or urine study
within 1 week, prior to registration to rule out pregnancy
- Women of childbearing potential and sexually active males are strongly advised
to use an accepted and effective method of contraception
- WBC >= 3500/mm^3
- ANC >= 1500/mm^3
- Platelet count >= 100,000/mm^3
- Total bilirubin < 1.5mg/dL
- SGPT and SGOT < 3 times institution's upper limit of normal
- Serum creatinine < 2mg/dl or creatinine clearance >= 20 ml/min