Neoadjuvant Chemoradiotherapy With or Without Gefitinib in Treating Patients With Stage IIIA or Stage IIIB Non-Small Cell Lung Cancer
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Biological therapies such as gefitinib may interfere with the growth of the tumor cells and slow the growth of the tumor. Combining chemotherapy and radiation therapy with gefitinib before surgery may shrink the tumor so that it can be removed during surgery.
PURPOSE: Phase I/II trial to compare the effectiveness of neoadjuvant chemoradiotherapy with or without gefitinib in treating patients who are undergoing surgery for stage III non-small cell lung cancer.
Drug: gemcitabine hydrochloride
Procedure: conventional surgery
Procedure: neoadjuvant therapy
Radiation: radiation therapy
|Study Design:||Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Neoadjuvant Chemoradiotherapy (Gemcitabine/Cisplatin and Taxotere) With or Without Co-Administration of ZD 1839 (Iressa) for Stage IIIA (N2) and Selective Stage IIIB Non-Small Cell Lung Cancer: Phase I-II Study|
- Determine the tolerability and toxicity of gefitinib in combination with chest radiotherapy in patients with stage IIIA or stage IIIB non-small cell lung cancer. [ Designated as safety issue: Yes ]
|Study Start Date:||May 2003|
|Study Completion Date:||September 2004|
|Primary Completion Date:||September 2004 (Final data collection date for primary outcome measure)|
OBJECTIVES: Phase I:
- Determine the tolerability and toxicity of gefitinib in combination with chest radiotherapy in patients with stage IIIA or stage IIIB non-small cell lung cancer.
- Compare the pathologic response (complete response and rate of downstaging) in patients treated with neoadjuvant chemoradiotherapy with vs without gefitinib.
- Compare the feasibility and toxicity profile of these regimens in these patients.
- Compare the resection rates, time to progression, and overall survival of patients treated with these regimens.
- Correlate the percent decline in the fludeoxyglucose F 18 standardized uptake value as measured by position emission tomography with pathologic response at resection, time to progression, and overall survival in patients treated with these regimens.
Phase I: This is an open-label, nonrandomized study.
- Induction: Patients receive cisplatin IV over 60 minutes on day 1 and gemcitabine IV over 30 minutes on days 1 and 8. Treatment repeats every 3 weeks for a total of 2 courses in the absence of disease progression or unacceptable toxicity.
- Consolidation: Within 3-4 weeks after the completion of induction therapy, patients undergo radiotherapy once daily 5 days a week for 5 weeks and receive oral gefitinib once daily concurrently.
A cohort of 3-6 patients receives consolidation chemoradiotherapy. If 2 of 6 patients experience dose-limiting toxicity, gefitinib is deleted from consolidation therapy in phase II arm II.
- Surgery: Patients without disease progression after consolidation therapy undergo thoracotomy within 3-5 weeks after consolidation.
Maintenance: Beginning 2-4 weeks after surgery, patients receive oral gefitinib once daily for 6 months in the absence of disease progression.
- Phase II: This is a randomized study. Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive induction and consolidation therapy (with the exception of gefitinib) as in phase I. Patients also receive docetaxel IV over 60 minutes concurrently with radiotherapy during consolidation. Patients undergo surgery as in phase I.
- Arm II: Patients receive therapy (including gefitinib) as in phase I. Patients also receive docetaxel IV over 60 minutes concurrently with radiotherapy during consolidation.
Patients are followed every 6-8 weeks for the first 12 months and then every 4-6 months thereafter.
PROJECTED ACCRUAL: A total of 43-80 patients (3-6 patients for phase I and 40-74 patients [20-37 per treatment arm] for phase II) will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00062270
|United States, Alabama|
|University of Alabama at Birmingham Comprehensive Cancer Center|
|Birmingham, Alabama, United States, 35294-3300|
|Study Chair:||Francisco Robert, MD, FACP||University of Alabama at Birmingham|