Pilot Neoadjuvant Study of ZD1839 (IRESSA®) as Single Agent Preoperative Therapy for Clinical Stage 1A and 1B (T1-2N0), II (T1-2N1, T3N0) and Selected IIIA (T3N1) Non-Small Cell Lung Cancer (NSCLC) With Molecular Correlates
- Determine the effects of neoadjuvant gefitinib on downstream signaling pathways,
including Src-Stat3, PI3K/Akt, ERK activity, and Bcl-2 family members in patients with
resectable stage I-IIIA non-small cell lung cancer.
- Determine the effects of this drug on cell cycle and apoptosis within the primary
tumor, by measuring changes in pre- and post-treatment Ki-67, Mcm2, cleaved caspase-3,
and ApoTag, in these patients.
- Determine the clinical response rate in patients treated with this drug.
- Determine the pathological response rate, defined as > 95% necrosis or fibrosis in the
pathological specimen, in patients treated with this drug.
- Determine the metabolic activity of this drug in these patients.
- Determine the safety, tolerability, and feasibility of this drug, in terms of toxicity
and post-treatment resectability, in these patients.
- Correlate plasma and tumor concentrations of this drug with changes in post-treatment
molecular markers in these patients.
- Identify a gene profile that predicts response to this drug in these patients.
OUTLINE: This is an open-label, pilot study.
Patients receive oral gefitinib once daily for 4 weeks in the absence of disease progression
or unacceptable toxicity.
Within 3 days after completion of gefitinib, patients undergo restaging evaluation. Patients
whose disease is still considered resectable proceed to surgery. Patients undergo
thoracotomy with lobectomy or pneumonectomy OR sleeve resection. Patients also undergo
mediastinal lymph node dissection. After surgical resection, treatment with gefitinib may
continue off study at the discretion of the principal investigator.
After completion of study therapy, patients are followed at 30 days, every 4 months for 1
year, every 6 months for 1 year, and then annually thereafter.
PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study within 12.5 months.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Overall Response Rate (ORR)
Objective Response Rate according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Investigators planned to use this pilot study of neoadjuvant ZD1839 in patients with resectable NSCLC to specifically correlate molecular parameters to the primary clinical study endpoint clinical response assessed by CT response and PET scan response of the primary tumor.
Eric B. Haura, M.D.
H. Lee Moffitt Cancer Center and Research Institute
United States: Food and Drug Administration
|H. Lee Moffitt Cancer Center and Research Institute||Tampa, Florida 33612|