This phase II clinical trial studies how well combining different regimens of chemotherapy and gefitinib with radiation therapy work in treating patients with stage III non-small cell lung cancer. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Biological therapies such as gefitinib may interfere with the growth of tumor cells and slow the growth of non-small cell lung cancer. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving different regimens of combination therapy together with gefitinib and radiation therapy may be an effective treatment for non-small cell lung cancer.
PRIMARY OBJECTIVES: I. To determine whether ZD1839 (gefitinib) at 250 mg orally every day administered concomitantly with radiotherapy after induction treatment consisting of paclitaxel, carboplatin, and ZD1839 among patients with inoperable stage III non-small cell lung cancer and Common Terminology Criteria (CTC) performance status 2 or poor risk performance status 0-1 is tolerable. II. To determine whether ZD1839 at 250 mg orally every day administered concomitantly with paclitaxel, carboplatin, and radiation after induction treatment consisting of paclitaxel, carboplatin, and ZD1839 among patients with inoperable stage III non-small cell lung cancer and CTC performance status 0-1 is tolerable. III. To determine the overall response rate, failure-free survival, and survival after treatment with induction chemotherapy with daily ZD1839, concomitant radiotherapy and daily ZD1839, and post-radiotherapy single agent daily ZD1839 among patients with CTC performance status 2 or poor risk performance status 0-1 and inoperable stage III non-small cell lung cancer. IV. To determine the overall response rate, failure-free survival, and survival after treatment with induction chemotherapy and daily ZD1839, concomitant chemoradiotherapy and daily ZD1839, and post-radiotherapy single agent daily ZD1839 among patients with CTC performance status 0-1 and inoperable stage III non-small cell lung cancer. V. To determine if elevated circulating epidermal growth factor receptor (EGFR) levels prior to treatment, as determined by either quantitative polymerase chain reaction (PCR) or direct enzyme-linked immunosorbent assay (ELISA) measurement, may predict for response to therapy with EGFR inhibitors. OUTLINE: All patients receive induction therapy comprising paclitaxel IV over 3 hours followed by carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 2 courses. Patients then receive therapy based on their assigned stratum. STRATUM I: Patients receive gefitinib orally (PO) daily for 7 weeks. Patients also undergo concurrent radiotherapy once daily 5 days a week for 7 weeks. STRATUM II: Patients receive gefitinib and radiotherapy as in stratum I concurrently with paclitaxel IV over 1 hour followed by carboplatin over 30 minutes once weekly for 7 weeks. Patients then receive gefitinib PO daily in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for 2 years.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
144
Given IV
Given IV
Given PO
Undergo radiotherapy
Optional correlative studies
Cancer and Leukemia Group B
Chicago, Illinois, United States
Overall survival (Stratum I)
Kaplan-Meier curves will be used to describe overall survival in each stratum.
Time frame: From randomization until death or last known follow-up, assessed up to 10 months
Overall survival (Stratum I)
Kaplan-Meier curves will be used to describe overall survival in each stratum.
Time frame: From randomization until death or last known follow-up, assessed up to 13 months
Overall survival (Stratum II)
Kaplan-Meier curves will be used to describe overall survival in each stratum.
Time frame: From randomization until death or last known follow-up, assessed up to 14.5 months
Toxicity as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
The frequency of toxicity occurrence will be tabulated by the most severe occurrence.
Time frame: Up to 3 years
Failure-free survival
Kaplan-Meier curves will be used to describe failure-free survival in each stratum. Within each treatment group, the pattern of treatment failure (local, distant, regional) will be summarized.
Time frame: Time between randomization and disease progression, death, or last known follow-up, assessed up to 3 years
Response to induction treatment
Summarized by treatment group. Exact binomial confidence intervals will be computed for these response rates.
Time frame: Up to 3 years
Overall response
Overall response to the full treatment regimen will be summarized by treatment group. Exact binomial confidence intervals will be computed for these response rates.
Time frame: Up to 3 years
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