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 bevacizumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Bevacizumab may also stop the growth of tumor cells by stopping blood flow to the tumor. Combining gemcitabine with bevacizumab may kill more tumor cells. It is not yet known whether gemcitabine is more effective with or without bevacizumab in treating pancreatic cancer.

PURPOSE: This randomized phase III trial is studying gemcitabine and bevacizumab to see how well they work compared to gemcitabine alone in treating patients with locally advanced or metastatic pancreatic cancer.

Condition	Treatment or Intervention	Phase
adenocarcinoma of the pancreas recurrent pancreatic cancer stage II pancreatic cancer stage III pancreatic cancer stage IVA pancreatic cancer stage IVB pancreatic cancer	Drug: bevacizumab  Drug: gemcitabine  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: growth factor antagonist therapy  Procedure: monoclonal antibody therapy	Phase III

Further Study Details: 

OBJECTIVES: Primary

• Compare survival of patients with locally advanced or metastatic adenocarcinoma of the pancreas treated with gemcitabine with vs without bevacizumab.

Secondary

• Compare objective response rate, duration of response, and progression-free survival of patients treated with these regimens.
• Compare the toxicity of these regimens in these patients.
• Correlate baseline levels of vascular endothelial growth factor (VEGF) with treatment outcome in patients treated with these regimens.
• Determine baseline and on-treatment levels of additional growth factors that may be co- or counter-regulated with VEGF and correlate these levels with response in patients treated with these regimens.
• Determine baseline and on-treatment levels of coagulation and endothelial cell activation markers that may predict thrombotic or bleeding risks in patients treated with these regimens.
• Compare the effects of these regimens on resource utilization, cost, and utilities.
• Determine estimates of marginal cost-utility.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to ECOG performance status (0-1 vs 2), disease extent (metastatic vs locally advanced), and prior radiotherapy (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15 and bevacizumab IV over 30-90 minutes on days 1 and 15.
• Arm II: Patients receive gemcitabine IV as in arm I and placebo IV over 30-90 minutes on days 1 and 15. In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 1 year and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 590 patients (295 per treatment arm) will be accrued for this study within 26.8 months.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed adenocarcinoma of the pancreas
• Locally advanced or metastatic disease
• Not amenable to curative resection
• No invasion of adjacent organs (e.g., duodenum or stomach) by CT scan
• No evidence of CNS disease, including primary brain tumor or brain metastasis

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Granulocyte count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• No other significant bleeding episodes within the past 6 months

Hepatic

• Bilirubin normal
• SGOT ≤ 2.5 times upper limit of normal (ULN)
• PT and INR ≤ 1.5 times ULN (except for patients on full-dose warfarin)
• No esophageal varices

Renal

• Creatinine ≤ 1.5 mg/dL OR
• Creatinine clearance ≥ 60 mL/min
• No proteinuria
• Patients with ≥ 1+ proteinuria must demonstrate < 1 g/dL of protein on 24-hour urine collection

Cardiovascular

• No clinically significant cardiovascular disease
• No uncontrolled hypertension (i.e., blood pressure > 150/90 mm Hg on medication)
• No arterial thromboembolic event within the past 6 months, including any of the following:
• Myocardial infarction
• Unstable angina pectoris
• Cerebrovascular accident
• Transient ischemic attack
• No New York Heart Association grade II-IV congestive heart failure
• No serious cardiac arrhythmia requiring medication
• No peripheral vascular disease ≥ grade 2
• No clinically significant peripheral artery disease (i.e., claudication on < 1 block)

Pulmonary

• No hemoptysis within the past 6 months

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for up to 3 months after study participation
• No upper or lower gastrointestinal bleeding within the past 6 months
• No serious or non-healing wound, ulcer, or bone fracture
• No serious active viral, fungal, or bacterial infection
• No infection requiring parenteral antibiotics
• No hypersensitivity to Chinese hamster ovary cell products or other recombinant antibodies
• No significant traumatic injury within the past 28 days
• No other active malignancy except nonmelanoma skin cancer

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior bevacizumab in the adjuvant or metastatic setting
• No other prior vascular endothelial growth factor inhibitors
• No concurrent prophylactic filgrastim (G-CSF) or sargramostim (GM-CSF)
• No concurrent pegfilgrastim

Chemotherapy

• See Radiotherapy
• More than 4 weeks since prior adjuvant chemotherapy and recovered
• Patients must have evidence of disease progression after adjuvant chemotherapy
• No prior chemotherapy for metastatic disease
• No prior gemcitabine in the adjuvant or metastatic setting
• No other concurrent chemotherapy agents

Endocrine therapy

• No concurrent hormones except steroids for adrenal failure, hormones for non-disease-related conditions (e.g., insulin for diabetes), or intermittent dexamethasone as an antiemetic

Radiotherapy

• Prior radiotherapy with or without a radiosensitizing dose of fluoropyrimidines allowed provided there is disease outside radiotherapy port
• At least 4 weeks since prior radiotherapy and recovered
• No concurrent palliative radiotherapy

Surgery

• More than 28 days since prior major surgical procedure or open biopsy
• More than 7 days since prior fine needle aspirations
• No concurrent major surgical procedures

Other

• More than 1 month since prior thrombolytic agent
• No concurrent thrombolytic agent
• Concurrent full-dose anticoagulants allowed provided the patient is maintained on a stable dose of warfarin with an in-range INR (between approximately 2-3) OR on a stable dose of low molecular weight heparin

Alabama
      Northeast Alabama Regional Medical Center, Anniston,  Alabama,  36207,  United States; Recruiting
California
      Naval Medical Center - San Diego, San Diego,  California,  92134-3202,  United States; Recruiting
      Rebecca and John Moores UCSD Cancer Center, La Jolla,  California,  92093-0658,  United States; Recruiting
      Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, Los Angeles,  California,  90048,  United States; Recruiting
      UCSF Comprehensive Cancer Center, San Francisco,  California,  94115,  United States; Recruiting
      Veterans Affairs Medical Center - San Diego, San Diego,  California,  92161,  United States; Recruiting
      Veterans Affairs Medical Center - San Francisco, San Francisco,  California,  94121,  United States; Recruiting
Delaware
      CCOP - Christiana Care Health Services, Newark,  Delaware,  19713,  United States; Recruiting
District of Columbia
      Lombardi Cancer Center at Georgetown University Medical Center, Washington,  District of Columbia,  20007,  United States; Recruiting
      Walter Reed Army Medical Center, Washington,  District of Columbia,  20307-5001,  United States; Recruiting
Florida
      Broward General Medical Center, Fort Lauderdale,  Florida,  33316,  United States; Recruiting
      CCOP - Mount Sinai Medical Center, Miami Beach,  Florida,  33140,  United States; Recruiting
      Florida Hospital Cancer Institute, Orlando,  Florida,  32804,  United States; Recruiting
      Memorial Cancer Institute at Memorial Regional Hospital, Hollywood,  Florida,  33021,  United States; Recruiting
      Palm Beach Cancer Institute - West Palm Beach, West Palm Beach,  Florida,  33401,  United States; Recruiting
Illinois
      CCOP - Evanston, Evanston,  Illinois,  60201,  United States; Recruiting
      CCOP - Illinois Oncology Research Association, Peoria,  Illinois,  61615-7828,  United States; Recruiting
      Center for Cancer Care at OSF Saint Anthony Medical Center, Rockford,  Illinois,  61108,  United States; Recruiting
      La Grange Oncology Associates, La Grange,  Illinois,  60525,  United States; Recruiting
      Louis A. Weiss Memorial Hospital, Chicago,  Illinois,  60640,  United States; Recruiting
      MBCCOP - University of Illinois at Chicago, Chicago,  Illinois,  60612,  United States; Recruiting
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States; Recruiting
      Veterans Affairs Medical Center - Chicago (Westside Hospital), Chicago,  Illinois,  60612,  United States; Recruiting
      West Suburban Center for Cancer Care, River Forest,  Illinois,  60305,  United States; Recruiting
Indiana
      CCOP - Northern Indiana CR Consortium, South Bend,  Indiana,  46601,  United States; Recruiting
      Fort Wayne Medical Oncology and Hematology, Incorporated, Fort Wayne,  Indiana,  46885-5099,  United States; Recruiting
Iowa
      Holden Comprehensive Cancer Center at University of Iowa, Iowa City,  Iowa,  52242-1009,  United States; Recruiting
Kentucky
      Baptist Hospital East - Louisville, Louisville,  Kentucky,  40207,  United States; Recruiting
Maryland
      Greenebaum Cancer Center at University of Maryland Medical Center, Baltimore,  Maryland,  21201,  United States; Recruiting
Massachusetts
      Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States; Recruiting
      UMASS Memorial Cancer Center - University Campus, Worcester,  Massachusetts,  01655,  United States; Recruiting
Michigan
      CCOP - Grand Rapids, Grand Rapids,  Michigan,  49503,  United States; Recruiting
      Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph, Saint Joseph,  Michigan,  49085,  United States; Recruiting
Minnesota
      University of Minnesota Cancer Center, Minneapolis,  Minnesota,  55455,  United States; Recruiting
      Veterans Affairs Medical Center - Minneapolis, Minneapolis,  Minnesota,  55417,  United States; Recruiting
Missouri
      CCOP - Kansas City, Kansas City,  Missouri,  64131,  United States; Recruiting
      Ellis Fischel Cancer Center at University of Missouri - Columbia, Columbia,  Missouri,  65203,  United States; Recruiting
      Missouri Baptist Cancer Center, Saint Louis,  Missouri,  63131,  United States; Recruiting
      Siteman Cancer Center at Barnes-Jewish Hospital, Saint Louis,  Missouri,  63110,  United States; Recruiting
Nebraska
      UNMC Eppley Cancer Center at the University of Nebraska Medical Center, Omaha,  Nebraska,  68198-7680,  United States; Recruiting
Nevada
      CCOP - Southern Nevada Cancer Research Foundation, Las Vegas,  Nevada,  89106,  United States; Recruiting
      Veterans Affairs Medical Center - Las Vegas, Las Vegas,  Nevada,  89106,  United States; Recruiting
New Hampshire
      Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center, Lebanon,  New Hampshire,  03756-0002,  United States; Recruiting
New Jersey
      Cancer Institute of New Jersey at the Cooper University Hospital, Camden,  New Jersey,  08103,  United States; Recruiting
New York
      CCOP - North Shore University Hospital, Manhasset,  New York,  11030,  United States; Recruiting
      CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C., East Syracuse,  New York,  13057,  United States; Recruiting
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States; Recruiting
      Mount Sinai Medical Center, New York,  New York,  10029,  United States; Recruiting
      New York Weill Cornell Cancer Center at Cornell University, New York,  New York,  10021,  United States; Recruiting
      North Shore University Hospital, Manhasset,  New York,  11030,  United States; Recruiting
      Queens Cancer Center of Queens Hospital, Jamaica,  New York,  11432,  United States; Recruiting
      Roswell Park Cancer Institute, Buffalo,  New York,  14263-0001,  United States; Recruiting
      SUNY Upstate Medical University Hospital, Syracuse,  New York,  13210,  United States; Recruiting
      Veterans Affairs Medical Center - Buffalo, Buffalo,  New York,  14215,  United States; Recruiting
      Veterans Affairs Medical Center - Syracuse, Syracuse,  New York,  13210,  United States; Recruiting
North Carolina
      Cape Fear Valley Medical Center, Fayetteville,  North Carolina,  28302-2000,  United States; Recruiting
      CCOP - Southeast Cancer Control Consortium, Goldsboro,  North Carolina,  27534-9479,  United States; Recruiting
      Comprehensive Cancer Center at Moore Regional Hospital, Pinehurst,  North Carolina,  28374,  United States; Recruiting
      Comprehensive Cancer Center at Wake Forest University, Winston Salem,  North Carolina,  27157-1082,  United States; Recruiting
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States; Recruiting
      Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill, Chapel Hill,  North Carolina,  27599-7295,  United States; Recruiting
      NorthEast Oncology Associates - Concord, Concord,  North Carolina,  28025,  United States; Recruiting
      Veterans Affairs Medical Center - Asheville, Asheville,  North Carolina,  28805-9913,  United States; Recruiting
      Veterans Affairs Medical Center - Durham, Durham,  North Carolina,  27705,  United States; Recruiting
      Zimmer Cancer Center at New Hanover Regional Medical Center, Wilmington,  North Carolina,  28402-9025,  United States; Recruiting
Ohio
      Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University, Columbus,  Ohio,  43210-1240,  United States; Recruiting
Oklahoma
      Oklahoma University Medical Center, Oklahoma City,  Oklahoma,  73104,  United States; Recruiting
Pennsylvania
      Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital, Pittsburgh,  Pennsylvania,  15224,  United States; Recruiting
Rhode Island
      Miriam Hospital at Lifespan, Providence,  Rhode Island,  02906,  United States; Recruiting
Texas
      Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas, Dallas,  Texas,  75390-8852,  United States; Recruiting
      Veterans Affairs Medical Center - Dallas, Dallas,  Texas,  75219,  United States; Recruiting
Vermont
      Vermont Cancer Center at University of Vermont, Burlington,  Vermont,  05401-3498,  United States; Recruiting
Virginia
      Martha Jefferson Hospital, Charlottesville,  Virginia,  22902,  United States; Recruiting
      MBCCOP - Massey Cancer Center, Richmond,  Virginia,  23298-0037,  United States; Recruiting
      Oncology and Hematology Associates of Southwest Virginia, Incorporated - Roanoke, Roanoke,  Virginia,  24014,  United States; Recruiting
      Virginia Oncology Associates - Norfolk, Norfolk,  Virginia,  23502,  United States; Recruiting
West Virginia
      St. Mary's Medical Center, Huntington,  West Virginia,  25701,  United States; Recruiting

Study chairs or principal investigators

Hedy L. Kindler, MD,  Study Chair,  University of Chicago Cancer Research Center   

Study ID Numbers:  CDR0000377542; CALGB-80303; ECOG-80303; NCT00088894
Record last reviewed:  February 2005
Last Updated:  April 5, 2005
Record first received:  August 4, 2004
ClinicalTrials.gov Identifier:  NCT00088894
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08