RATIONALE: Drugs used in chemotherapy use 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. Combining chemotherapy and monoclonal antibodies may kill more tumor cells.

PURPOSE: Randomizedphase II/III trial to study the effectiveness of combination chemotherapy with or without bevacizumab in treating patients who have advanced, metastatic, or recurrentnon-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	Drug: bevacizumab  Drug: carboplatin  Drug: paclitaxel  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 II Phase III

Further Study Details: 

OBJECTIVES:

• Compare the toxicity of paclitaxel and carboplatin with or without bevacizumab in patients with advanced, metastatic, or recurrent non-squamous cell non-small cell lung cancer.
• Compare the survival of patients treated with these regimens.
• Compare the response rates and time to progression in patients treated with these regimens.

OUTLINE: This is a randomized study. Patients are stratified according to measurable disease (yes vs no), prior radiotherapy (yes vs no), weight loss (less than 5% vs 5% or more), and disease stage (IIIB vs IV vs recurrent). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive paclitaxel IV over 3 hours followed by carboplatin IV over 15-30 minutes on day 1.
• Arm II: Patients receive paclitaxel and carboplatin as in arm I followed by bevacizumab IV over 30-90 minutes on day 1. Treatment in both arms repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of 6 courses, patients in arm II with stable or responding disease continue to receive bevacizumab only. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 842 patients will be accrued for this study.

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)
• Stage IIIB with malignant pleural effusion, stage IV, or recurrent
• Measurable or nonmeasurable disease
• No squamous cell NSCLC
• No known CNS metastases by head CT scan or MRI within the past 4 weeks

PATIENT CHARACTERISTICS: Age:

• 18 and over

Performance status:

• ECOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• No prior thrombotic or hemorrhagic disorders

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• Transaminases no greater than 5 times upper limit of normal (ULN)
• PTT normal
• INR no greater than 1.5

Renal:

• Creatinine no greater than 1.5 times ULN
• Urine protein less than 1+ (i.e., trace or 0 by dipstick or urinalysis) OR
• 24-hour urine protein less than 500 mg

Cardiovascular:

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• Concurrent hypertension allowed provided well-controlled on a stable regimen of anti-hypertensive therapy

Pulmonary:

• No history of gross hemoptysis (½ teaspoon of bright red blood or more)

Other:

• No ongoing or active infection
• No serious non-healing wound ulcer
• No bone fracture
• No psychiatric illness or social situation that would preclude study compliance
• No other concurrent comorbidities that would preclude study participation
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy:

• At least 3 weeks since prior immunotherapy and recovered

Chemotherapy:

• No prior systemic chemotherapy

Endocrine therapy:

• At least 3 weeks since prior hormonal therapy and recovered

Radiotherapy:

• At least 3 weeks since prior radiotherapy and recovered

Surgery:

• At least 3 weeks since prior major surgery

Other:

• No concurrent therapeutic anticoagulation
• No concurrent chronic daily aspirin (greater than 325 mg/day)
• No concurrent non-steroidal anti-inflammatory agents known to inhibit platelet function (arm II only)
• No concurrent dipyridamole, ticlopidine, clopidogrel, and/or cilostazol

Alabama
      Comprehensive Cancer Institute, Huntsville,  Alabama,  35801,  United States
      Northeast Alabama Regional Medical Center, Anniston,  Alabama,  36207,  United States
California
      Stanford Cancer Center at Stanford University Medical Center, Stanford,  California,  94305-5216,  United States
      Veterans Affairs Medical Center - San Diego, San Diego,  California,  92161,  United States
Colorado
      Boulder Community Hospital, Boulder,  Colorado,  80301-9019,  United States
      CCOP - Colorado Cancer Research Program, Incorporated, Denver,  Colorado,  80224,  United States
      Longmont United Hospital, Longmont,  Colorado,  80501,  United States
      Medical Center of Aurora - South Campus, Aurora,  Colorado,  80012-0000,  United States
      Penrose Cancer Center, Colorado Springs,  Colorado,  80933,  United States
      Porter Adventist Hospital, Denver,  Colorado,  80210,  United States
      Presbyterian-St Luke's Medical Center, Denver,  Colorado,  80218,  United States
      Rocky Mountain Cancer Centers - Rose, Denver,  Colorado,  80220,  United States
      Rocky Mountain Cancer Centers, Thornton,  Colorado,  80260,  United States
      St. Joseph Hospital, Denver,  Colorado,  80218-1191,  United States
      St. Mary-Corwin Regional Medical Center, Pueblo,  Colorado,  81004,  United States
Delaware
      CCOP - Christiana Care Health Services, Newark,  Delaware,  19713,  United States
District of Columbia
      Veterans Affairs Medical Center - Washington, DC, Washington,  District of Columbia,  20422,  United States
Florida
      Broward General Medical Center, Fort Lauderdale,  Florida,  33316,  United States
      Florida Hospital Cancer Institute, Orlando,  Florida,  32804,  United States
      Memorial Regional Hospital Comprehensive Cancer Center, Hollywood,  Florida,  33021,  United States
      Palm Beach Cancer Institute, West Palm Beach,  Florida,  33401,  United States
Illinois
      CCOP - Central Illinois, Decatur,  Illinois,  62526,  United States
      CCOP - Evanston, Evanston,  Illinois,  60201,  United States
      CCOP - Illinois Oncology Research Association, Peoria,  Illinois,  61602,  United States
      Louis A. Weiss Memorial Hospital, Chicago,  Illinois,  60640,  United States
      Robert H. Lurie Comprehensive Cancer Center at Northwestern University, Chicago,  Illinois,  60611,  United States
      Saint Anthony Medical Center, Rockford,  Illinois,  61108,  United States
      West Suburban Center for Cancer Care, River Forest,  Illinois,  60305,  United States
Indiana
      Fort Wayne Medical Oncology and Hematology, Incorporated, Fort Wayne,  Indiana,  46885-5099,  United States
Iowa
      CCOP - Iowa Oncology Research Association, Des Moines,  Iowa,  50309-1016,  United States
Kentucky
      Baptist Hospital East - Louisville, Louisville,  Kentucky,  40207,  United States
Louisiana
      CCOP - Ochsner, New Orleans,  Louisiana,  70121,  United States
      MBCCOP - LSU Health Sciences Center, New Orleans,  Louisiana,  70112,  United States
Maryland
      Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,  Maryland,  21231,  United States
      Veterans Affairs Medical Center - Baltimore, Baltimore,  Maryland,  21201,  United States
Massachusetts
      Beth Israel Deaconess Medical Center, Boston,  Massachusetts,  02215,  United States
Michigan
      CCOP - Kalamazoo, Kalamazoo,  Michigan,  49007-3731,  United States
      CCOP - Michigan Cancer Research Consortium, Ann Arbor,  Michigan,  48106,  United States
      Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph, Saint Joseph,  Michigan,  49085,  United States
Minnesota
      CCOP - Duluth, Duluth,  Minnesota,  55805,  United States
      CCOP - Metro-Minnesota, Saint Louis Park,  Minnesota,  55416,  United States
      Veterans Affairs Medical Center - Minneapolis, Minneapolis,  Minnesota,  55417-2399,  United States
Missouri
      Ellis Fischel Cancer Center at University of Missouri - Columbia, Columbia,  Missouri,  65203,  United States
Nevada
      CCOP - Southern Nevada Cancer Research Foundation, Las Vegas,  Nevada,  89106,  United States
      Veterans Affairs Medical Center - Las Vegas, Las Vegas,  Nevada,  89106,  United States
New Jersey
      Cooper University Hospital, Camden,  New Jersey,  08103,  United States
      Veterans Affairs Medical Center - East Orange, East Orange,  New Jersey,  07019,  United States
New Mexico
      MBCCOP - University of New Mexico HSC, Albuquerque,  New Mexico,  87131,  United States
New York
      Albert Einstein Clinical Cancer Center, Bronx,  New York,  10461,  United States
      Elmhurst Hospital Center, Elmhurst,  New York,  11373,  United States
      Queens Cancer Center of Queens Hospital, Jamaica,  New York,  11432,  United States
North Carolina
      Cape Fear Valley Health System, Fayetteville,  North Carolina,  28302-2000,  United States
      FirstHealth Moore Regional Hospital, Pinehurst,  North Carolina,  28374,  United States
      Lenoir Memorial Hospital Cancer Center, Kinston,  North Carolina,  28503-1678,  United States
      New Hanover Regional Medical Center, Wilmington,  North Carolina,  28402-9025,  United States
      NorthEast Oncology Associates, Concord,  North Carolina,  28025,  United States
      Veterans Affairs Medical Center - Asheville, Asheville,  North Carolina,  28805,  United States
North Dakota
      CCOP - Merit Care Hospital, Fargo,  North Dakota,  58122,  United States
      Veterans Affairs Medical Center - Fargo, Fargo,  North Dakota,  58102,  United States
Ohio
      MetroHealth Medical Center, Cleveland,  Ohio,  44109,  United States
Oklahoma
      CCOP - Oklahoma, Tulsa,  Oklahoma,  74136,  United States
Pennsylvania
      CCOP - Geisinger Clinic and Medical Center, Danville,  Pennsylvania,  17822-2001,  United States
      CCOP - MainLine Health, Wynnewood,  Pennsylvania,  19096,  United States
      Fox Chase Cancer Center, Philadelphia,  Pennsylvania,  19111-2497,  United States
South Dakota
      CCOP - Sioux Community Cancer Consortium, Sioux Falls,  South Dakota,  57104,  United States
Tennessee
      Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center, Nashville,  Tennessee,  37232-6307,  United States
Texas
      CCOP - Scott and White Hospital, Temple,  Texas,  76508,  United States
      Veterans Affairs Medical Center - Dallas, Dallas,  Texas,  75216,  United States
Virginia
      Martha Jefferson Hospital, Charlottesville,  Virginia,  22902,  United States
      Oncology and Hematology Associates of Southwest Virginia, Inc., Roanoke,  Virginia,  24014,  United States
      Virginia Oncology Associates - Norfolk, Norfolk,  Virginia,  23502,  United States
West Virginia
      St. Mary's Medical Center, Huntington,  West Virginia,  25701,  United States
Wisconsin
      CCOP - Marshfield Clinic Research Foundation, Marshfield,  Wisconsin,  54449,  United States
      CCOP - St. Vincent Hospital Cancer Center, Green Bay, Green Bay,  Wisconsin,  54307-3453,  United States
      Ministry Medical Group - Northern Region, Rhinelander,  Wisconsin,  54501,  United States
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792-0001,  United States
Puerto Rico
      University of Puerto Rico School of Medicine Medical Sciences Campus, San Juan,  00936-5067,  Puerto Rico
South Africa
      Pretoria Academic Hospital, Pretoria,  0001,  South Africa

Study chairs or principal investigators

Alan B. Sandler, MD,  Study Chair,  Vanderbilt-Ingram Cancer Center   
Michael C. Perry, MD,  Study Chair,  Ellis Fischel Cancer Center at University of Missouri - Columbia   

Study ID Numbers:  CDR0000068744; ECOG-4599; CTSU; CALGB-E4599
Record last reviewed:  May 2004
Last Updated:  October 13, 2004
Record first received:  July 11, 2001
ClinicalTrials.gov Identifier:  NCT00021060
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08