Phase II Study to Evaluate the Tumor Biochemical Effects of the EGFR Tyrosine Kinase Inhibitor OSI-774 (Erlotinib) Administered Prior to Surgical Resection in Patients With Early Stage Non-Small Cell Lung Cancer
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.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Biochemical response rate in tumor defined as > 75% decrease in P-MAPK and/or P-AKT
Up to 5 years
Eastern Cooperative Oncology Group
United States: Food and Drug Administration
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