RATIONALE: Drugs used in chemotherapy, such as gemcitabine, 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. It is not yet known whether gemcitabine is more effective with or without cetuximab in treating pancreatic cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of gemcitabine with or without cetuximab as first-line therapy in treating patients who have locally advanced unresectable or metastatic adenocarcinoma of the pancreas.

Condition	Treatment or Intervention	Phase
adenocarcinoma of the pancreas stage III pancreatic cancer stage IVA pancreatic cancer stage IVB pancreatic cancer	Drug: cetuximab  Drug: gemcitabine  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: monoclonal antibody therapy	Phase III

Further Study Details: 

OBJECTIVES:

• Compare the overall survival of patients with locally advanced unresectable or metastatic adenocarcinoma of the pancreas treated with gemcitabine and cetuximab vs gemcitabine alone.
• Compare the time to treatment failure in patients treated with these regimens.
• Estimate the percentage of patients with epidermal growth factor receptor (EGFR) tumor expression in patients treated with these regimens.
• Compare the overall survival of patients in the EGFR-positive subset treated with these regimens.
• Compare the toxicity of these regimens in these patients.
• Compare the total response rate (confirmed and unconfirmed complete and partial response) in patients with measurable disease treated with these regimens.
• Compare the patient report of pain and quality of life of patients treated with these regimens.

OUTLINE: This is an open-label, randomized, multicenter study. Patients are stratified according to disease status (locally advanced unresectable vs metastatic), Zubrod performance status (0 or 1 vs 2), and prior pancreatectomy (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive cetuximab IV over 1-2 hours on days 1, 8, 15, and 22 and gemcitabine IV over 30 minutes on days 1, 8, 15, and 22 for course 1 and days 1, 8, and 15 for all subsequent courses.
• Arm II: Patients receive gemcitabine as in arm I. In both arms, courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, before each course, and at the end of study therapy.

Patients are followed every 6 months for 2 years and then annually for 1 year.

PROJECTED ACCRUAL: A total of 704 patients (352 per treatment arm) will be accrued for this study within 5 years.

Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed pancreatic adenocarcinoma meeting 1 of the following criteria:
• Locally advanced unresectable disease
• Distant metastatic disease
• Measurable or nonmeasurable disease by x-ray, scan, or physical examination
• Tumor tissue must be submitted for evaluation of epidermal growth factor receptor expression before study entry
• No endocrine tumors or lymphoma of the pancreas
• No known brain metastases

PATIENT CHARACTERISTICS: Age

• Not specified

Performance status

• Zubrod 0-2

Life expectancy

• At least 3 months

Hematopoietic

• Absolute granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than 2.0 times upper limit of normal (ULN)
• SGOT or SGPT no greater than 2.5 times ULN

Renal

• Creatinine no greater than 2.0 mg/dL

Cardiovascular

• No significant history of cardiac disease
• No uncontrolled hypertension
• No unstable angina
• No congestive heart failure

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• HIV negative
• 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 that is currently in remission

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior immunotherapy for advanced pancreatic cancer
• No prior cetuximab or other therapy that targets the epidermal growth factor pathway
• No prior chimerized or murine monoclonal antibody therapy
• No other concurrent anticancer immunotherapy

Chemotherapy

• No prior chemotherapy or chemoradiotherapy for advanced pancreatic cancer
• At least 6 months since prior adjuvant chemotherapy
• No other concurrent anticancer chemotherapy

Endocrine therapy

• No prior hormonal therapy for advanced pancreatic cancer
• No concurrent anticancer hormonal therapy

Radiotherapy

• See Chemotherapy
• At least 28 days since prior radiotherapy and recovered
• Prior palliative radiotherapy to metastatic sites allowed
• No concurrent anticancer radiotherapy, including whole brain radiotherapy for progressive disease (i.e., CNS metastasis)

Surgery

• At least 14 days since prior pancreatic cancer surgery and recovered

Other

• No other concurrent anticancer therapy

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
      La Grange Oncology Associates, La Grange,  Illinois,  60525,  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
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 - 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
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
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
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

Philip A. Philip, MD, PhD, FRCP,  Barbara Ann Karmanos Cancer Institute   

Study ID Numbers:  CDR0000347414; SWOG-S0205; NCT00075686
Record last reviewed:  February 2005
Last Updated:  April 4, 2005
Record first received:  January 9, 2004
ClinicalTrials.gov Identifier:  NCT00075686
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08