RATIONALE: Drugs used in chemotherapy, such as carboplatin and gemcitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Celecoxib and zileuton may stop the growth of tumor cells by stopping blood flow to the tumor and may block the enzymes necessary for tumor cell growth. Combining chemotherapy with celecoxib and/or zileuton may kill more tumor cells.

PURPOSE: Randomized phase II trial to study the effectiveness of combining celecoxib and/or zileuton with carboplatin and gemcitabine in treating patients who have advanced non-small cell lung cancer.

Condition	Treatment or Intervention	Phase
stage IV non-small cell lung cancer Adenocarcinoma of the Lung Squamous Cell Lung Cancer large cell lung cancer stage IIIB non-small cell lung cancer	Drug: carboplatin  Drug: celecoxib  Drug: gemcitabine  Drug: zileuton  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: enzyme inhibitor therapy  Procedure: growth factor antagonist therapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Compare the efficacy of carboplatin and gemcitabine with celecoxib and/or zileuton, in terms of 7-month progression-free survival, in patients with advanced non-small cell lung cancer.

Secondary

• Compare the response rate, distribution of survival, and failure-free survival time of patients treated with these regimens.
• Correlate CYFRA and serum vascular endothelial growth factor levels with response and survival of patients treated with these regimens.
• Correlate cyclo-oxygenase-2 and 5-lipoxygenase expression with survival of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 3 treatment arms.

• Arm I: Patients receive gemcitabine IV over 30 minutes on days 1 and 8, carboplatin IV over 30 minutes on day 1, and oral zileuton 4 times daily on days 1-21.
• Arm II: Patients receive gemcitabine and carboplatin as in arm I and oral celecoxib twice daily on days 1-21.
• Arm III: Patients receive gemcitabine and carboplatin as in arm I, oral celecoxib as in arm II, and oral zileuton as in arm I. In all arms, treatment repeats every 21 days for 6 courses. Patients with responding or stable disease continue courses of zileuton and/or celecoxib in the absence of disease progression or unacceptable toxicity.

Patients are followed monthly for 1 year, every 2 months for 2 years, and then every 4 months for 3 years or until disease progression.

PROJECTED ACCRUAL: A total of 117 patients (39 per treatment arm) will be accrued for this study within 11-12 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 1 of the following cellular types:
• Adenocarcinoma
• Large cell
• Squamous cell
• Mixed
• Meets 1 of the following staging criteria:
• Stage IIIB disease with malignant pleural effusion, supraclavicular node involvement, or contralateral hilar nodes
• Stage IIIB patients eligible for Cancer and Leukemia Group B protocols of combined chemotherapy and chest irradiation are not allowed
• Stage IV disease
• Measurable or nonmeasurable disease
• Unidimensionally measurable lesions at least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
• The following are considered nonmeasurable disease:
• Bone lesions
• Ascites
• Pleural/pericardial effusion
• Lymphangitis cutis/pulmonis
• Abdominal masses that are not confirmed and followed by imaging techniques
• Cystic lesions
• Small lesions
• No leptomeningeal disease
• Symptomatic CNS metastases must be treated (e.g., surgery, radiotherapy, or gamma knife), neurologically stable, and off steroids

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

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

Hepatic

• Bilirubin no greater than 1.5 mg/dL
• AST no greater than 2.0 times upper limit of normal

Renal

• Creatinine no greater than 1.5 mg/dL

Cardiovascular

• None of the following within the past 6 months:
• Myocardial infarction
• Unstable angina
• Symptomatic congestive heart failure
• Serious uncontrolled cardiac arrhythmia
• Cerebrovascular accident
• Transient ischemic attack
• Symptomatic carotid artery or peripheral vascular disease
• Deep vein thrombosis
• Significant thromboembolic event

Pulmonary

• No pulmonary embolism within the past 6 months

Gastrointestinal

• No history of gastrointestinal (GI) bleeding
• No history of peptic ulcer disease
• No active GI bleeding

Other

• Not pregnant or nursing
• No known hypersensitivity to aspirin, NSAIDs, or sulfonamides
• No currently active second malignancy other than nonmelanoma skin cancer
• Patients are not considered to have a currently active malignancy if they have completed therapy and are considered by their physician to be at less than 30% risk of relapse

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior immunotherapy for NSCLC

Chemotherapy

• No prior chemotherapy for NSCLC
• No other concurrent chemotherapy

Endocrine therapy

• See Disease Characteristics
• No concurrent chronic oral steroids
• Concurrent episodic steroids for antiemetic purposes allowed
• No concurrent hormonal therapy
• Concurrent inhaled steroids allowed when medically indicated
• Concurrent megestrol for appetite stimulation is allowed

Radiotherapy

• See Disease Characteristics
• At least 2 weeks since prior radiotherapy and recovered

Surgery

• See Disease Characteristics
• At least 2 weeks since prior surgery and recovered

Other

• No prior systemic treatments for NSCLC
• No other concurrent investigational therapy
• At least 1 week since prior nonsteroidal anti-inflammatory drugs (NSAIDs), including any of the following:
• Rofecoxib
• Choline magnesium trisalicylate
• Ibuprofen
• Naproxen
• Etodolac
• Oxaprozin
• Diflunisal
• Nabumetone
• Tolmetin
• Valdecoxib
• No concurrent NSAIDs
• No concurrent chronic aspirin
• Concurrent aspirin no greater than 325 mg/day is allowed
• No concurrent fluconazole
• No concurrent leukotriene antagonists (e.g., zafirlukast, montelukast, or pranlukast)

Alabama
      Northeast Alabama Regional Medical Center, Anniston,  Alabama,  36207,  United States
California
      Cedars-Sinai Comprehensive Cancer Center at Cedars-Sinai Medical Center, Los Angeles,  California,  90048,  United States
      Naval Medical Center - San Diego, San Diego,  California,  92134-3202,  United States
      Rebecca and John Moores UCSD Cancer Center, La Jolla,  California,  92093-0658,  United States
      UCSF Comprehensive Cancer Center, San Francisco,  California,  94115,  United States
      Veterans Affairs Medical Center - San Diego, San Diego,  California,  92161,  United States
      Veterans Affairs Medical Center - San Francisco, San Francisco,  California,  94121,  United States
Delaware
      CCOP - Christiana Care Health Services, Newark,  Delaware,  19713,  United States
District of Columbia
      Lombardi Cancer Center at Georgetown University Medical Center, Washington,  District of Columbia,  20007,  United States
      Veterans Affairs Medical Center - Washington, DC, Washington,  District of Columbia,  20422,  United States
      Walter Reed Army Medical Center, Washington,  District of Columbia,  20307-5001,  United States
Florida
      Broward General Medical Center, Fort Lauderdale,  Florida,  33316,  United States
      CCOP - Mount Sinai Medical Center, Miami Beach,  Florida,  33140,  United States
      Memorial Regional Cancer Center at Memorial Regional Hospital, Hollywood,  Florida,  33021,  United States
      Palm Beach Cancer Institute, West Palm Beach,  Florida,  33401,  United States
Illinois
      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
      MBCCOP - University of Illinois at Chicago, Chicago,  Illinois,  60612,  United States
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States
      Veterans Affairs Medical Center - Chicago (Westside Hospital), Chicago,  Illinois,  60612,  United States
      West Suburban Center for Cancer Care, River Forest,  Illinois,  60305,  United States
Indiana
      CCOP - Northern Indiana CR Consortium, South Bend,  Indiana,  46601,  United States
      Fort Wayne Medical Oncology and Hematology, Incorporated, Fort Wayne,  Indiana,  46885-5099,  United States
Iowa
      Holden Comprehensive Cancer Center at University of Iowa, Iowa City,  Iowa,  52242-1009,  United States
Kentucky
      Baptist Hospital East - Louisville, Louisville,  Kentucky,  40207,  United States
Maryland
      Greenebaum Cancer Center at University of Maryland Medical Center, Baltimore,  Maryland,  21201,  United States
Massachusetts
      Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States
      University of Massachusetts Memorial Medical Center - University Campus, Worcester,  Massachusetts,  01655,  United States
Michigan
      Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph, Saint Joseph,  Michigan,  49085,  United States
Minnesota
      University of Minnesota Cancer Center, Minneapolis,  Minnesota,  55455,  United States
      Veterans Affairs Medical Center - Minneapolis, Minneapolis,  Minnesota,  55417,  United States
Missouri
      CCOP - Kansas City, Kansas City,  Missouri,  64131,  United States
      Ellis Fischel Cancer Center at University of Missouri - Columbia, Columbia,  Missouri,  65203,  United States
      Missouri Baptist Cancer Center, Saint Louis,  Missouri,  63131,  United States
      Siteman Cancer Center, Saint Louis,  Missouri,  63110,  United States
      Veterans Affairs Medical Center - Columbia (Truman Memorial), Columbia,  Missouri,  65201,  United States
Nebraska
      UNMC Eppley Cancer Center at the University of Nebraska Medical Center, Omaha,  Nebraska,  68198-7680,  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 Hampshire
      New Hampshire Oncology-Hematology, PA - Hooksett, Hooksett,  New Hampshire,  03106,  United States
      Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center, Lebanon,  New Hampshire,  03756-0002,  United States
New Jersey
      Cooper University Hospital, Camden,  New Jersey,  08103,  United States
New York
      CCOP - North Shore University Hospital, Manhasset,  New York,  11030,  United States
      CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C., East Syracuse,  New York,  13057,  United States
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States
      Mount Sinai Medical Center, New York,  New York,  10029,  United States
      New York Weill Cornell Cancer Center at Cornell University, New York,  New York,  10021,  United States
      North Shore University Hospital, Manhasset,  New York,  11030,  United States
      Queens Cancer Center of Queens Hospital, Jamaica,  New York,  11432,  United States
      University Hospital at State University of New York - Upstate Medical University, Syracuse,  New York,  13210,  United States
      Veterans Affairs Medical Center - Buffalo, Buffalo,  New York,  14215,  United States
      Veterans Affairs Medical Center - Syracuse, Syracuse,  New York,  13210,  United States
North Carolina
      Cape Fear Valley Health System, Fayetteville,  North Carolina,  28302-2000,  United States
      CCOP - Southeast Cancer Control Consortium, Goldsboro,  North Carolina,  27534-9479,  United States
      Comprehensive Cancer Center at Wake Forest University, Winston Salem,  North Carolina,  27157-1082,  United States
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States
      FirstHealth Moore Regional Hospital, Pinehurst,  North Carolina,  28374,  United States
      Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill, Chapel Hill,  North Carolina,  27599-7295,  United States
      NorthEast Oncology Associates - Concord, Concord,  North Carolina,  28025,  United States
      Veterans Affairs Medical Center - Asheville, Asheville,  North Carolina,  28805,  United States
      Veterans Affairs Medical Center - Durham, Durham,  North Carolina,  27705,  United States
      Zimmer Cancer Center at New Hanover Regional Medical Center, Wilmington,  North Carolina,  28402-9025,  United States
Ohio
      Arthur G. James Cancer Hospital at Ohio State University, Columbus,  Ohio,  43210-1240,  United States
Oklahoma
      Oklahoma University Medical Center, Oklahoma City,  Oklahoma,  73104,  United States
Pennsylvania
      Western Pennsylvania Hospital, Pittsburgh,  Pennsylvania,  15224,  United States
Rhode Island
      Lifespan: The Miriam Hospital, Providence,  Rhode Island,  02906,  United States
Texas
      Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas, Dallas,  Texas,  75390-8852,  United States
      Veterans Affairs Medical Center - Dallas, Dallas,  Texas,  75219,  United States
Vermont
      Vermont Cancer Center at University of Vermont, Burlington,  Vermont,  05401-3498,  United States
Virginia
      Martha Jefferson Hospital, Charlottesville,  Virginia,  22902,  United States
      MBCCOP - Massey Cancer Center, Richmond,  Virginia,  23298-0037,  United States
      Oncology and Hematology Associates of Southwest Virginia, Incorporated - Roanoke, 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

Study chairs or principal investigators

Martin J. Edelman, MD,  Study Chair,  University of Maryland Greenebaum Cancer Center   

Study ID Numbers:  CDR0000334573; CALGB-30203
Record last reviewed:  November 2004
Last Updated:  November 4, 2004
Record first received:  October 3, 2003
ClinicalTrials.gov Identifier:  NCT00070486
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08