RATIONALE: Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as cetuximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining more than one chemotherapy drug with a monoclonal antibody may kill more tumor cells. It is not yet known whether cetuximab is more effective when given at the same time as chemotherapy or following chemotherapy. PURPOSE: This randomized phase II trial is studying how well giving cetuximab at the same time as combination chemotherapy works compared to giving cetuximab after combination chemotherapy in treating patients with stage IIIB or stage IV non-small cell lung cancer.
OBJECTIVES: Primary * Compare overall survival of patients with selected stage IIIB or stage IV non-small cell lung cancer treated with concurrent vs sequential paclitaxel, carboplatin, and cetuximab. Secondary * Compare response rates (confirmed and unconfirmed, complete and partial) in patients treated with these regimens. * Compare the toxic effects of these regimens in these patients. * Correlate epidermal growth factor receptor polymorphisms and downstream biomarkers with response to cetuximab in these patients. OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms. * Arm I (concurrent cetuximab): Patients receive cetuximab IV over 1 hour (over 2 hours on day 1 of course 1 only) on days 1, 8, and 15 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 8. Treatment repeats every 21 days for a total of 4 courses (12 weeks) in the absence of disease progression or unacceptable toxicity. Beginning on week 13, patients receive single-agent cetuximab IV over 1 hour once weekly in the absence of disease progression or unacceptable toxicity. * Arm II (sequential cetuximab): Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses (12 weeks) in the absence of disease progression or unacceptable toxicity. Beginning on week 13, patients receive single-agent cetuximab IV over 1 hour (over 2 hours on week 13 only) once weekly in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 1 year and then every 6 months for 2 years. PROJECTED ACCRUAL: A total of 180 patients (90 per treatment arm) will be accrued for this study within 9 months.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
242
Arm 1: 400 mg/m2 (Initial dose), 2 hour IV infusion on Day 1, Week 1 only. 250 mg/m2 (Subsequent doses), 1 hour IV infusion, on Day 1 weekly starting at Week 2. Arm 2: 400 mg/m2 (Initial dose), 2 hour IV infusion on Week 13 ONLY 250 mg/m2 (Subsequent doses), 1 hour IV infusion, weekly starting at Week 14.
Arm 1: AUC=6 30 minute IV infusion immediately following paclitaxel on Day 1 q 21 days x 4 starting at Week 2 Arm 2: AUC=6 30 minute IV infusion immediately following paclitaxel on Day 1 q 21 days x 4 starting at Week 1
Arm 1: 225 mg/m2 3 hour IV infusion 1 hour following cetuximab on Day 1, q 21 days x 4 Starting at Week 4. Arm 2: 225 mg/m2 3 hour IV infusion 1 hour following cetuximab on Day 1, q 21 days x 4 Starting at Week 1.
Alaska Regional Hospital
Anchorage, Alaska, United States
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
Alta Bates Comprehensive Cancer Center
Berkeley, California, United States
Peninsula Medical Center
Burlingame, California, United States
City of Hope Comprehensive Cancer Center
Duarte, California, United States
Select a regimen based on overall survival
To select a regimen based on overall survival via a Phase II selection design of chemotherapy in conjunction with cetuximab (concurrent vs. sequential) for Phase III testing against chemotherapy alone in Stage IIIB and Stage IV non-small cell lung cancer.
Time frame: From date of registration until the date of progression or date of death from any cause, whichever came first, assessed up to 3 years
Response rate (confirmed and unconfirmed, complete and partial response)
To evaluate response rates (confirmed and unconfirmed, complete and partial) of patients with selected Stage IIIB and Stage IV NSCLC treated with paclitaxel and carboplatin with concurrent cetuximab or paclitaxel and carboplatin followed by cetuximab.
Time frame: From date of registration until the date of progression or date of death from any cause, whichever came first, assessed up to 3 years
Toxicities
To evaluate the toxicities of the two treatment regimens in patients with selected Stage IIIB and Stage IV NSCLC.
Time frame: From date of registration until the date of progression or date of death from any cause, whichever came first, assessed up to 3 years
Correlation of epidermal growth factor receptor polymorphisms and downstream biomarkers with response
To conduct exploratory molecular correlative studies of the EGFR-HER signaling pathways examining activated phosphoproteins, oncogenic mutations and rates of proliferation and apoptosis in patient tissues (see S9925 for details).
Time frame: At prestudy
Evaluate EGFR polymorphisms
To evaluate EGFR polymorphisms as a potential correlate for response to cetuximab (see S9925 for details).
Time frame: At prestudy and week 5
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Marin Cancer Institute at Marin General Hospital
Greenbrae, California, United States
Sutter Health Western Division Cancer Research Group
Greenbrae, California, United States
Saint Rose Hospital
Hayward, California, United States
Valley Memorial Hospital
Livermore, California, United States
USC/Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, United States
...and 153 more locations