Phase II Randomized Open-Label Trial of the EGFR Tyrosine Kinase Inhibitor OSI-774 (Tarceva™) in Combination With Paclitaxel and Carboplatin Prior to Surgery in Resectable Stage IIIA (N2) and IIIB (T4 N2) NSCLC: A Clinical Outcome and Biological Endpoint Trial
This is a phase II, single institution open label randomized trial of induction carboplatin
and paclitaxel plus/minus daily oral OSI-774 in patients with potentially resectable NSCLC
that is stage IIIA and IIIB (T4 satellite nodules or invasion into T4 structures but no
malignant effusion.) N3 disease is excluded. Patients will be required to have
pathologically demonstrated N2 disease via mediastinoscopy. Forty patients will be treated
with 3 courses of chemotherapy followed by surgery. Ten of these patients will be
randomized to chemotherapy alone and 30 patients to chemotherapy plus OSI-774. The 10
patients will serve as a chemotherapy alone control for molecular endpoint analysis.
OSI-774 will be stopped the night before surgery. At the time of surgery, pathologic
response will be determined. Following surgery, patients will be treated with consolidation
radiation therapy if there are positive margins or N2 lymph nodes at the time of resection.
Patients who have no N2 disease at surgery will have the option of consolidation radiation
therapy but will not be required to have it done. Patients not able to tolerate radiation
even if they have N2 disease or positive margins at surgery may continue on this study. This
will be followed by maintenance OSI-774 for patients from both arms of the study. OSI-774
will be continued as maintenance to a maximum of 2 years following surgery. Tissue for
molecular studies will be obtained pretreatment either at the time of diagnostic biopsy or
mediastinoscopy. Post-treatment tissue will be obtained at the time of surgery. This
tissue will be assayed for defined molecular endpoints using immunohistochemistry,
immunoprecipitation and mRNA expression analysis. Blood, urine, hair follicles, and skin
samples will also be collected from patients who consent to provide these.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Number of Patients With Response
Response defined by tumor assessment using Response Evaluation Criteria In Solid Tumors (RECIST) to learn effectiveness of Tarceva (OSI-774) when combined with standard chemotherapy before surgery.
5 Years to collect outcome information
Ralph Zinner, MD
M.D. Anderson Cancer Center
United States: Food and Drug Administration
|MD Anderson Cancer Center||Houston, Texas 77030-4096|