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: Randomized phase II trial to compare the effectiveness of giving cetuximab at the same time as combination chemotherapy with that of cetuximab given after combination chemotherapy in treating patients who have stage IIIB or stage IV non-small cell lung cancer.

Condition	Treatment or Intervention	Phase
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	Drug: carboplatin  Drug: cetuximab  Drug: paclitaxel  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: monoclonal antibody therapy	Phase II

Further Study Details: 

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.
• 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.

Secondary

• 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 for up to 1 year 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 for up to 1 year 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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

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 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

Alabama
      MBCCOP - Gulf Coast, Mobile,  Alabama,  36607,  United States; Recruiting
Arizona
      Arizona Cancer Center at University of Arizona Health Sciences Center, Tucson,  Arizona,  85724,  United States; Recruiting
      CCOP - Western Regional, Arizona, Phoenix,  Arizona,  85006-2726,  United States; Recruiting
      Veterans Affairs Medical Center - Phoenix (Carl T. Hayden), Phoenix,  Arizona,  85012,  United States; Recruiting
      Veterans Affairs Medical Center - Tucson, Tucson,  Arizona,  85723,  United States; Recruiting
Arkansas
      Arkansas Cancer Research Center at University of Arkansas for Medical Sciences, Little Rock,  Arkansas,  72205,  United States; Recruiting
      Veterans Affairs Medical Center - Little Rock, Little Rock,  Arkansas,  72205,  United States; Recruiting
California
      CCOP - Bay Area Tumor Institute, Oakland,  California,  94609-3305,  United States; Recruiting
      CCOP - Santa Rosa Memorial Hospital, Santa Rosa,  California,  95403,  United States; Recruiting
      Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center, Orange,  California,  92868,  United States; Recruiting
      City of Hope Comprehensive Cancer Center, Duarte,  California,  91010-3000,  United States; Recruiting
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1781,  United States; Recruiting
      USC/Norris Comprehensive Cancer Center and Hospital, Los Angeles,  California,  90033,  United States; Recruiting
      Veterans Affairs Medical Center - Loma Linda (Pettis), Loma Linda,  California,  92357,  United States; Recruiting
      Veterans Affairs Outpatient Clinic - Martinez, Martinez,  California,  94553,  United States; Recruiting
Colorado
      University of Colorado Cancer Center at University of Colorado Health Sciences Center, Aurora,  Colorado,  80010,  United States; Recruiting
      Veterans Affairs Medical Center - Denver, Denver,  Colorado,  80220,  United States; Recruiting
District of Columbia
      MBCCOP - Howard University Cancer Center, Washington,  District of Columbia,  20060,  United States; Recruiting
Florida
      Veterans Affairs Medical Center - Tampa (Haley), Tampa,  Florida,  33612,  United States; Recruiting
Georgia
      CCOP - Atlanta Regional, Atlanta,  Georgia,  30342-1701,  United States; Recruiting
Hawaii
      MBCCOP - Hawaii, Honolulu,  Hawaii,  96813,  United States; Recruiting
Illinois
      Cardinal Bernardin Cancer Center at Loyola University Medical Center, Maywood,  Illinois,  60153-5500,  United States; Recruiting
      CCOP - Central Illinois, Decatur,  Illinois,  62526,  United States; Recruiting
      MBCCOP - University of Illinois at Chicago, Chicago,  Illinois,  60612,  United States; Recruiting
      Veterans Affairs Medical Center - Chicago (Westside Hospital), Chicago,  Illinois,  60612,  United States; Recruiting
      Veterans Affairs Medical Center - Hines, Hines,  Illinois,  60141,  United States; Recruiting
Kansas
      CCOP - Wichita, Wichita,  Kansas,  67214-3882,  United States; Recruiting
      Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center, Kansas City,  Kansas,  66160-7390,  United States; Recruiting
      Veterans Affairs Medical Center - Wichita, Wichita,  Kansas,  67218,  United States; Recruiting
Kentucky
      Markey Cancer Center at University of Kentucky Chandler Medical Center, Lexington,  Kentucky,  40536-0084,  United States; Recruiting
      Veterans Affairs Medical Center - Lexington, Lexington,  Kentucky,  40502-2236,  United States; Recruiting
Louisiana
      Louisiana State University Health Sciences Center - Shreveport, Shreveport,  Louisiana,  71130-3932,  United States; Recruiting
      MBCCOP - LSU Health Sciences Center, New Orleans,  Louisiana,  70112,  United States; Recruiting
      Tulane Cancer Center at Tulane University Hospital and Clinic, New Orleans,  Louisiana,  70112,  United States; Recruiting
      Veterans Affairs Medical Center - New Orleans, New Orleans,  Louisiana,  70112,  United States; Recruiting
      Veterans Affairs Medical Center - Shreveport, Shreveport,  Louisiana,  71101-4295,  United States; Recruiting
Massachusetts
      Cancer Research Center at Boston Medical Center, Boston,  Massachusetts,  02118,  United States; Recruiting
      Veterans Affairs Medical Center - Boston (Jamaica Plain), Jamaica Plain,  Massachusetts,  02130,  United States; Recruiting
Michigan
      Barbara Ann Karmanos Cancer Institute, Detroit,  Michigan,  48201-1379,  United States; Recruiting
      CCOP - Beaumont, Royal Oak,  Michigan,  48073-6769,  United States; Recruiting
      CCOP - Grand Rapids, Grand Rapids,  Michigan,  49503,  United States; Recruiting
      CCOP - Michigan Cancer Research Consortium, Ann Arbor,  Michigan,  48106,  United States; Recruiting
      Josephine Ford Cancer Center at Henry Ford Health System, Detroit,  Michigan,  48202,  United States; Recruiting
      Providence Cancer Institute at Providence Hospital - Southfield, Southfield,  Michigan,  48075,  United States; Recruiting
      University of Michigan Comprehensive Cancer Center, Ann Arbor,  Michigan,  48109-0948,  United States; Recruiting
      Veterans Affairs Medical Center - Detroit, Detroit,  Michigan,  48201-1932,  United States; Recruiting
Mississippi
      University of Mississippi Medical Center, Jackson,  Mississippi,  39216-4505,  United States; Recruiting
      Veterans Affairs Medical Center - Biloxi, Biloxi,  Mississippi,  39531-2410,  United States; Recruiting
      Veterans Affairs Medical Center - Jackson, Jackson,  Mississippi,  39216,  United States; Recruiting
Missouri
      CCOP - Cancer Research for the Ozarks, Springfield,  Missouri,  65807,  United States; Recruiting
      CCOP - Kansas City, Kansas City,  Missouri,  64131,  United States; Recruiting
      CCOP - St. Louis-Cape Girardeau, Saint Louis,  Missouri,  63141,  United States; Recruiting
      Saint Louis University Cancer Center, Saint Louis,  Missouri,  63110,  United States; Recruiting
      Veterans Affairs Medical Center - Kansas City, Kansas City,  Missouri,  64128,  United States; Recruiting
Montana
      CCOP - Montana Cancer Consortium, Billings,  Montana,  59101,  United States; Recruiting
New Mexico
      MBCCOP - University of New Mexico HSC, Albuquerque,  New Mexico,  87131,  United States; Recruiting
      Veterans Affairs Medical Center - Albuquerque, Albuquerque,  New Mexico,  87108-5138,  United States; Recruiting
New York
      Herbert Irving Comprehensive Cancer Center at Columbia University, New York,  New York,  10032,  United States; Recruiting
      James P. Wilmot Cancer Center at University of Rochester Medical Center, Rochester,  New York,  14642,  United States; Recruiting
      NYU Cancer Institute at New York University Medical Center, New York,  New York,  10016,  United States; Recruiting
North Carolina
      CCOP - Southeast Cancer Control Consortium, Goldsboro,  North Carolina,  27534-9479,  United States; Recruiting
Ohio
      CCOP - Columbus, Columbus,  Ohio,  43206,  United States; Recruiting
      CCOP - Dayton, Dayton,  Ohio,  45429,  United States; Recruiting
      Charles M. Barrett Cancer Center at University Hospital, Cincinnati,  Ohio,  45267-0501,  United States; Recruiting
      Cleveland Clinic Taussig Cancer Center, Cleveland,  Ohio,  44195-9001,  United States; Recruiting
      Veterans Affairs Medical Center - Cincinnati, Cincinnati,  Ohio,  45220-2288,  United States; Recruiting
      Veterans Affairs Medical Center - Dayton, Dayton,  Ohio,  45428-1002,  United States; Recruiting
Oklahoma
      Oklahoma University Medical Center, Oklahoma City,  Oklahoma,  73104,  United States; Recruiting
Oregon
      Cancer Institute at Oregon Health and Science University, Portland,  Oregon,  97201-3098,  United States; Recruiting
      CCOP - Columbia River Oncology Program, Portland,  Oregon,  97225,  United States; Recruiting
      Veterans Affairs Medical Center - Portland, Portland,  Oregon,  97207,  United States; Recruiting
South Carolina
      CCOP - Greenville, Greenville,  South Carolina,  29615,  United States; Recruiting
      CCOP - Upstate Carolina, Spartanburg,  South Carolina,  29303,  United States; Recruiting
      Hollings Cancer Center at Medical University of South Carolina, Charleston,  South Carolina,  29425,  United States; Recruiting
      Veterans Affairs Medical Center - Charleston, Charleston,  South Carolina,  29401-5799,  United States; Recruiting
Tennessee
      University of Tennessee Cancer Institute at Methodist Central Hospital, Memphis,  Tennessee,  38104,  United States; Recruiting
      Veterans Affairs Medical Center - Memphis, Memphis,  Tennessee,  38104,  United States; Recruiting
Texas
      Brooke Army Medical Center, Fort Sam Houston,  Texas,  78234-6200,  United States; Recruiting
      CCOP - Scott and White Hospital, Temple,  Texas,  76508,  United States; Recruiting
      Harrington Cancer Center, Amarillo,  Texas,  79106,  United States; Recruiting
      MD Anderson Cancer Center at University of Texas, Houston,  Texas,  77030-4095,  United States; Recruiting
      University of Texas Health Science Center at San Antonio, San Antonio,  Texas,  78229-3900,  United States; Recruiting
      University of Texas Medical Branch, Galveston,  Texas,  77555-0565,  United States; Recruiting
      Veterans Affairs Medical Center - Amarillo, Amarillo,  Texas,  79106,  United States; Recruiting
      Veterans Affairs Medical Center - San Antonio (Murphy), San Antonio,  Texas,  78229,  United States; Recruiting
      Veterans Affairs Medical Center - Temple, Temple,  Texas,  76504,  United States; Recruiting
Utah
      Huntsman Cancer Institute at University of Utah, Salt Lake City,  Utah,  84112-5550,  United States; Recruiting
      Veterans Affairs Medical Center - Salt Lake City, Salt Lake City,  Utah,  84148,  United States; Recruiting
Virginia
      MBCCOP - Massey Cancer Center, Richmond,  Virginia,  23298-0037,  United States; Recruiting
      Sentara Cancer Institute at Sentara Norfolk General Hospital, Norfolk,  Virginia,  23510-1115,  United States; Recruiting
Washington
      CCOP - Northwest, Tacoma,  Washington,  98405-0986,  United States; Recruiting
      CCOP - Virginia Mason Research Center, Seattle,  Washington,  98101,  United States; Recruiting
      Puget Sound Oncology Consortium, Seattle,  Washington,  98109,  United States; Recruiting
      Veterans Affairs Medical Center - Seattle, Seattle,  Washington,  98108,  United States; Recruiting

Study chairs or principal investigators

Roy Herbst, MD, PhD,  M.D. Anderson Cancer Center   
Karen Kelly, MD,  University of Colorado Cancer Center   
David R. Gandara, MD,  University of California Davis Cancer Center   

Study ID Numbers:  CDR0000370806; SWOG-S0342; NCT00085501
Record last reviewed:  September 2004
Last Updated:  April 4, 2005
Record first received:  June 10, 2004
ClinicalTrials.gov Identifier:  NCT00085501
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08