RATIONALE: Pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Cetuximab may also make tumor cells more sensitive to radiation therapy. Giving pemetrexed disodium, carboplatin, and radiation therapy together with cetuximab may kill more tumor cells. PURPOSE: This randomized phase II trial is studying how well giving pemetrexed disodium and carboplatin together with radiation therapy with or without cetuximab works in treating patients with stage III non-small cell lung cancer that cannot be removed by surgery.
OBJECTIVES: Primary * Determine the overall survival of patients with unresectable stage III non-small cell lung cancer treated with pemetrexed disodium, carboplatin, and thoracic radiotherapy with or without cetuximab. Secondary * Determine the failure-free survival and response rates in patients treated with these regimens. * Correlate epidermal growth factor receptor, erbB2, and K-ras mutations with survival and tumor response in patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. * Chemoradiotherapy (courses 1-4): Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive pemetrexed disodium IV over 10 minutes followed by carboplatin IV over 30 minutes on days 1, 22, 43, and 64. Patients also undergo thoracic radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47. * Arm II: Patients receive pemetrexed disodium, carboplatin, and thoracic radiotherapy as in arm I. Patients also receive cetuximab IV over 2 hours on day 1 and then IV over 1 hour on days 8, 15, 22, 29, 36, and 43. * Consolidation chemotherapy (courses 5-8): Beginning 3-5 weeks after completion of chemoradiotherapy, all patients receive consolidation chemotherapy comprising pemetrexed disodium alone IV over 10 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for up to 3 years. PROJECTED ACCRUAL: A total of 100 patients (50 per treatment arm) will be accrued for this study within 10-13 months.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
109
400 mg/sq m IV over 120 min: Day 1; Week 1 250 mg/sq m IV over 60 min weekly for 6 more weeks.
AUC = 5 q 21 days for 4 cycles
500 mg/sq m IV q 21 days during chemoradiation and consolidation chemotherapy phases
Thoracic radiotherapy: 70 Gy for 7 weeks beginning on Day 1.
Arroyo Grande Community Hospital
Arroyo Grande, California, United States
Eden Medical Center
Castro Valley, California, United States
Saint Rose Hospital
Hayward, California, United States
Rebecca and John Moores UCSD Cancer Center
La Jolla, California, United States
Highland General Hospital
Oakland, California, United States
18 Month Survival
Percentage of participants who were alive at 18 months. The 18 month survival, with 95% CI, was estimated using the Kaplan-Meier method.
Time frame: 18 months (from randomization)
Failure-free Survival
Failure-free survival (FFS) is the time from randomization to a failure event, defined as disease progression or death from any cause (which ever occurred first). The median FFS with 95% CI was estimated using the Kaplan-Meier method,
Time frame: Time from randomization to failure (up to 4 years)
Number of Participants With Overall Tumor Response
Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: * Complete Response (CR): disappearance of all target lesions; * Partial Response (PR) 30% decrease in sum of longest diameter of target lesions; * Progressive Disease (PD): 20% increase in sum of longest diameter of target lesions; * Stable Disease (SD): small changes that do not meet above criteria. Overall tumor response is the total number of CR and PRs.
Time frame: Duration of study until progression (up to 4 years)
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