Neoadjuvant IRESSA As Single Agent PreopTherapy for NSCLC With Molecular Correlates
RATIONALE: Gefitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving gefitinib before surgery may shrink the tumor so it can be removed.
PURPOSE: This phase II trial is studying how well gefitinib works in treating patients who are undergoing surgery for stage I, stage II, or stage III non-small cell lung cancer.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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|
- Overall Response Rate (ORR) [ Time Frame: 3 years ] [ Designated as safety issue: No ]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.
- Frequency of Toxicity Related to Study Treatment [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]Review of adverse events utilizing Common Toxicity Criteria (CTC) V3. To estimate the safety, tolerability, and feasibility of preoperative ZD1839 in patients with resectable Stage IA/IB, II and selected IIIA NSCLC by evaluating toxicity and operability after preoperative ZD1839.
|Study Start Date:||October 2004|
|Study Completion Date:||March 2009|
|Primary Completion Date:||May 2008 (Final data collection date for primary outcome measure)|
Experimental: Neoadjuvant ZD1839 Preoperative Therapy
The ZD1839 250-mg tablet will be taken once a day, every day about the same time. It can be taken with or without food.
At the time of surgery, investigators will collect tissue from the participant's tumor once it has been removed. This tissue will be used to study the effect of ZD1839 on tumor growth.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00104728
|United States, Florida|
|H. Lee Moffitt Cancer Center and Research Institute|
|Tampa, Florida, United States, 33612-9497|
|Principal Investigator:||Eric B. Haura, M.D.||H. Lee Moffitt Cancer Center and Research Institute|