Lung Cancer
Conditions
Keywords
recurrent non-small cell lung cancer, stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer, adenocarcinoma of the lung, squamous cell lung cancer, large cell lung cancer
Brief summary
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.
Detailed description
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.
Interventions
DRUGcetuximab
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.
DRUGcarboplatin
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
DRUGpaclitaxel
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.
Sponsors
National Cancer Institute (NCI)
SWOG Cancer Research Network
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) of one of the following stages: * Newly diagnosed selected stage IIIB disease (T4 lesion due to malignant pleural effusion, any N, M0) * Newly diagnosed stage IV disease (any T, any N, M1) * Recurrent stage IV disease after prior surgery or radiotherapy * The following subtypes are eligible: * Adenocarcinoma * Squamous cell carcinoma * Large cell carcinoma * Unspecified * Measurable disease by CT scan, MRI, x-ray, or physical exam * Pleural effusions, ascites, or laboratory parameters are not acceptable as the only evidence of disease * Not within prior radiotherapy field unless a new lesion is present * Not within area of prior surgical resection * No known brain metastases by CT scan or MRI PATIENT CHARACTERISTICS: Age * 18 and over Performance status * Zubrod 0-1 Life expectancy * Not specified Hematopoietic * Absolute neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Hemoglobin ≥ 9 mg/dL Hepatic * Bilirubin ≤ 2 times upper limit of normal (ULN) * SGOT or SGPT ≤ 2 times ULN * Alkaline phosphatase ≤ 2 times ULN * No known acute hepatitis Renal * Creatinine ≤ ULN * Creatinine clearance ≥ 50 mL/min Cardiovascular * No significant cardiac disease * No uncontrolled hypertension * No unstable angina * No congestive heart failure Other * No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer currently in complete remission * No active or uncontrolled infection * No sensory neuropathy ≥ grade 2 * No known human anti-mouse antibodies * Not pregnant or nursing * Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy * No prior biologic therapy for NSCLC * No prior chimeric or murine monoclonal antibody therapy * No prior cetuximab Chemotherapy * No prior systemic chemotherapy for NSCLC Endocrine therapy * Not specified Radiotherapy * See Disease Characteristics * At least 3 weeks since prior radiotherapy and recovered Surgery * See Disease Characteristics * At least 2 weeks since prior thoracic or major surgery and recovered Other * No prior gefitinib or other investigational agents that target the epidermal growth factor receptor pathway
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Select a regimen based on overall survival | From date of registration until the date of progression or date of death from any cause, whichever came first, assessed up to 3 years | 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. |
| Response rate (confirmed and unconfirmed, complete and partial response) | From date of registration until the date of progression or date of death from any cause, whichever came first, assessed up to 3 years | 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. |
| Toxicities | From date of registration until the date of progression or date of death from any cause, whichever came first, assessed up to 3 years | To evaluate the toxicities of the two treatment regimens in patients with selected Stage IIIB and Stage IV NSCLC. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation of epidermal growth factor receptor polymorphisms and downstream biomarkers with response | At prestudy | 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). |
| Evaluate EGFR polymorphisms | At prestudy and week 5 | To evaluate EGFR polymorphisms as a potential correlate for response to cetuximab (see S9925 for details). |
Countries
United States
Outcome results
None listed