RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether giving paclitaxel and carboplatin with BMS-275291 is more effective than giving paclitaxel and carboplatin alone for non-small cell lung cancer. PURPOSE: Randomized phase II/III trial to compare the effectiveness of paclitaxel and carboplatin with or without BMS-275291 in treating patients who have advanced or metastatic non-small cell lung cancer.

Condition	Treatment or Intervention	Phase
stage IV non-small cell lung cancer stage IIIB non-small cell lung cancer	Procedure: chemotherapy  Procedure: biological response modifier therapy  Procedure: growth factor antagonist therapy  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Drug: BMS-275291  Drug: carboplatin  Drug: paclitaxel	Phase II Phase III

Further Study Details: 

OBJECTIVES: I. Compare the overall survival of patients with advanced or metastatic non-small cell lung cancer when treated with paclitaxel and carboplatin with or without BMS-275291. II. Compare the incidence of grade 2 or higher drug related arthritis, arthralgia and/or myalgia in these patients when treated with these regimens. III. Compare the objective tumor response rate, time to response, and response duration in these patients when treated with these regimens. IV. Compare the nature, severity, and frequency of toxicities of these regimens in these patients. V. Compare the progression free survival of these patients when treated with these regimens. VI. Correlate the expression of tissue matrix metalloproteinases (MMP) levels with outcomes and response in these patients when treated with these regimens.

PROTOCOL OUTLINE: This is a randomized, double blind, placebo controlled, multicenter study. Patients are stratified according to center, disease stage (IIIB vs IV), and ECOG performance status (0-1 vs 2). Patients are randomized to one of two treatment arms. Arm I: Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 plus oral BMS-275291 daily on days 1-21. Arm II: Patients receive paclitaxel and carboplatin as in arm I plus oral placebo daily on days 1-21. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. BMS-275291 or placebo continues beyond 8 courses in the absence of disease progression. Patients are followed every 3 months for 2 years and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 700 patients (60 for phase II and 640 for phase III) will be accrued for this study within 2 years.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

Histologically or cytologically confirmed stage IIIB or IV non-small cell lung cancer (NSCLC)

• Local or metastatic failure following surgery and/or radiotherapy allowed

Phase II only:

• Measurable disease (At least 20 mm by conventional techniques or 10 mm by spiral CT scan)

No known CNS metastases unless asymptomatic and at least 4 weeks since prior corticosteroid therapy

--Prior/Concurrent Therapy--

Biologic therapy:

• No prior immunotherapy
• No prior biological response modifiers
• No concurrent biologic therapy or immunotherapy

Chemotherapy:

• No prior antineoplastic chemotherapy, including intrapleural chemotherapy
• No other concurrent cytotoxic anticancer therapy

Endocrine therapy: See Disease Characteristics

Radiotherapy:

• See Disease Characteristics
• No prior radiotherapy to study lesion (unless evidence of disease progression) or to 30% or greater of marrow bearing bones
• At least 1 week since prior radiotherapy and recovered
• No concurrent radiotherapy

Surgery:

• See Disease Characteristics
• At least 2 weeks since prior major surgery
• No concurrent surgery

Other:

• At least 2 weeks since prior investigational drug
• No other investigational drug during and for 30 days after study

--Patient Characteristics--

Age: 18 and over

Performance status: ECOG 0-2

Life expectancy: At least 12 weeks

Hematopoietic:

• Absolute granulocyte count at least 1,500/mm3
• Platelet count at least 100,000/mm3

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• ALT no greater than 2 times ULN (5 times ULN for liver metastases)

Renal: Creatinine no greater than 1.5 times ULN

Cardiovascular:

• No significant cardiac disease
• No uncontrolled high blood pressure, unstable angina, congestive heart failure, second or third degree atrioventricular conductions defect, or ventricular arrhythmias requiring medication
• No myocardial infarction within past year

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No prior allergic reaction to drugs containing Cremophor EL
• No serious active infection or other underlying medical condition that would preclude study
• No peripheral neuropathy
• No condition (e.g., psychological, geographical) that would preclude study
• No prior breast cancer or melanoma
• No other prior malignancy in past 5 years except carcinoma in situ, basal or squamous cell skin cancer, or other cancer that has been curatively treated surgically

Alabama
      University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham,  Alabama,  35294-3300,  United States
Arkansas
      University of Arkansas for Medical Sciences, Little Rock,  Arkansas,  72205,  United States
California
      Scripps Clinic, La Jolla,  California,  92037,  United States
Georgia
      Central Georgia Hematology Oncology, P.C., Macon,  Georgia,  31201,  United States
Hawaii
      Queen's Medical Center, Honolulu,  Hawaii,  96813,  United States
Illinois
      Carle Cancer Center, Urbana,  Illinois,  61801,  United States
Massachusetts
      Lahey Clinic - Burlington, Burlington,  Massachusetts,  01805,  United States
Nebraska
      Creighton University Cancer Center, Omaha,  Nebraska,  68131-2197,  United States
North Carolina
      Duke University Medical Center, Durham,  North Carolina,  27710,  United States
Oklahoma
      University of Oklahoma Health Sciences Center, Oklahoma City,  Oklahoma,  73190,  United States
Tennessee
      Baptist Regional Cancer Center - Knoxville, Knoxville,  Tennessee,  37901,  United States
      Division of Medical Oncology - Vanderbilt, Nashville,  Tennessee,  37232-5536,  United States
      Erlanger Health Systems, Chattanooga,  Tennessee,  37403,  United States
      Jackson-Madison County General Hospital, Jackson,  Tennessee,  38301,  United States
      Meharry Medical College, Nashville,  Tennessee,  37208-3599,  United States
      Memorial Hospital Cancer Center - Chattanooga, Chattanooga,  Tennessee,  37404,  United States
      Saint Thomas Hospital, Nashville,  Tennessee,  37205,  United States
      Williamson Medical Center, Franklin,  Tennessee,  37068-1600,  United States
Austria
      AKH Vienna, Vienna (Wien),  A-1090,  Austria
      Allgemeines Krankenhaus der Stadt Wien, Vienna (Wien),  A-1090,  Austria
Belgium
      Algemeen Ziekenhuis Sint-Augustinus, Wilrijk,  2610,  Belgium
      Centre Hospitalier Regional de la Citadelle, Liege (Luik),  4000,  Belgium
      Universiteit Gent, Gent,  B-9000,  Belgium
Canada, Alberta
      Cross Cancer Institute, Edmonton,  Alberta,  T6G 1Z2,  Canada
Canada, Manitoba
      CancerCare Manitoba, Winnipeg,  Manitoba,  R3E 0V9,  Canada
Canada, Nova Scotia
      Nova Scotia Cancer Centre, Halifax,  Nova Scotia,  B3H 1V7,  Canada
Canada, Ontario
      Algoma District Medical Group, Sault Sainte Marie,  Ontario,  P6B 1Y5,  Canada
      Cancer Care Ontario - Windsor Regional Cancer Centre, Windsor,  Ontario,  N8W 2X3,  Canada
      Cancer Care Ontario-Hamilton Regional Cancer Centre, Hamilton,  Ontario,  L8V 5C2,  Canada
      Hotel Dieu Health Sciences Hospital - Niagara, St. Catharines,  Ontario,  L2R 5K3,  Canada
      Humber River Regional Hospital, Weston,  Ontario,  M9N 1N8,  Canada
      Mount Sinai Hospital - Toronto, Toronto,  Ontario,  M5G 1X5,  Canada
      Ottawa Regional Cancer Centre, Ottawa,  Ontario,  K1H 1C4,  Canada
      Peterborough Oncology Clinic, Peterborough,  Ontario,  K9H 7B6,  Canada
      Royal Victoria Hospital, Barrie, Barrie,  Ontario,  L4M 6M2,  Canada
      Saint Joseph's Health Centre - Toronto, Toronto,  Ontario,  M6R 1B5,  Canada
      Toronto General Hospital, Toronto,  Ontario,  M5G 2C4,  Canada
      Toronto Sunnybrook Regional Cancer Centre, Toronto,  Ontario,  M4N 3M5,  Canada
Canada, Saskatchewan
      Allan Blair Cancer Centre, Regina,  Saskatchewan,  S4T 7T1,  Canada
      Saskatoon Cancer Centre, Saskatoon,  Saskatchewan,  S7N 4H4,  Canada
Finland
      Helsinki University Central Hospital, Helsinki,  FIN-0-0029,  Finland
France
      Centre Hospitalier Universitaire Bretonneau de Tours, Tours,  37044,  France
      CHR de Besancon - Hopital Jean Minjoz, Besancon,  25030,  France
      CHR de Grenoble - La Tronche, Grenoble,  38043,  France
      CRLCC Nantes - Atlantique, Nantes-Saint Herblain,  44805,  France
      Hopital Avicenne, Bobigny,  93009,  France
      Hopital de Neuhof, Strasbourg,  67091,  France
      Institut Claudius Regaud, Toulouse,  31052,  France
Germany
      Allgemeines Krankenhaus, Hamburg,  DOH-2-1075,  Germany
      Klinikum Rechts Der Isar/Technische Universitaet Muenchen, Munich (Muenchen),  D-81675,  Germany
      Lungenklinik Hemer, Hemer,  D-58675,  Germany
      Marienhospital/Ruhr University Bochum, Herne,  DOH-4-4625,  Germany
      Stadisches Krankenhaus Martha Maria Halle-Dolau, Halle,  06120,  Germany
Italy
      Istituto Clinico Humanitas, Rozzano (MI),  20089,  Italy
      Oncologia Medica - Perugia, Perugia,  06122,  Italy
      Ospedale Carlo Forlanini, Rome,  00149,  Italy
      Ospedale Civile San Giovanni e Paolo, Venezia,  30122,  Italy
      Ospedale San Filippo Neri, Rome,  00135,  Italy
Netherlands
      Academisch Ziekenhuis Maastricht, Maastricht,  6202 AZ,  Netherlands
Poland
      Medical University of Gdansk, Gdansk,  80-211,  Poland
Portugal
      Centro Hospitalar de Vila Nova de Gaia, Vila Nova de Gaia,  4434-502,  Portugal
Spain
      Hospital Universitario 12 de Octubre, Madrid,  28041,  Spain
      Hospital Universitario Marques de Valdecilla, Santander,  39008,  Spain
      Servicio De Oncologia, Valencia,  46017,  Spain
Switzerland
      Inselspital, Bern, Bern,  CH-3010,  Switzerland
      Kantonspital Aarau, AARAU,  5001,  Switzerland
      Universitaetsspital, Zurich,  CH-8091,  Switzerland
United Kingdom
      Chelsea Westminster Hospital, London,  SW10 9NH,  United Kingdom
United Kingdom, England
      Charing Cross Hospital, London,  England,  W6 8RF,  United Kingdom

Study chairs or principal investigators

Michael Smylie,  Study Chair,  National Cancer Institute of Canada   

Study ID Numbers:  CDR0000068153; CAN-NCIC-BR18; BMS-CA161-003
Record last reviewed:  July 2003
Last Updated:  October 13, 2004
Record first received:  September 11, 2000
ClinicalTrials.gov Identifier:  NCT00006229
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08