Paclitaxel and Carboplatin With or Without BMS-275291 in Treating Patients With Advanced or Metastatic Non-small Cell Lung Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00006229
First received: September 11, 2000
Last updated: November 11, 2013
Last verified: August 2011
  Purpose

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 paclitaxel and carboplatin are more effective with or without BMS-275291 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 Intervention Phase
Lung Cancer
Drug: carboplatin
Drug: paclitaxel
Drug: rebimastat
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Phase II/III Double Blind Randomized Trial of BMS-275291 vs. Placebo in Patients Receiving Paclitaxel/Carboplatin Chemotherapy for the Treatment of Advanced or Metastatic Non-small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by NCIC Clinical Trials Group:

Enrollment: 774
Study Start Date: April 2000
Study Completion Date: February 2009
Primary Completion Date: December 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BMS-275291 Drug: carboplatin Drug: paclitaxel Drug: rebimastat
Placebo Comparator: Placebo Drug: carboplatin Drug: paclitaxel

Detailed Description:

OBJECTIVES:

  • Compare the overall survival of patients with advanced or metastatic non-small cell lung cancer treated with paclitaxel and carboplatin with or without BMS-275291.
  • Compare the incidence of grade 2 or higher drug related arthritis, arthralgia and/or myalgia in patients treated with these regimens. (Phase II only)
  • Compare the objective tumor response rate, time to response, and response duration in patients treated with these regimens.
  • Compare the nature, severity, and frequency of toxic effects of these regimens in these patients.
  • Compare the progression free survival of patients treated with these regimens. (Phase III only)
  • Correlate the expression of serum/plasma and tissue matrix metalloproteinases (MMP) levels and other markers with outcomes and response in patients treated with these regimens.
  • Compare quality of life of patients treated with these regimens.

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.

Quality of life is assessed.

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

PROJECTED ACCRUAL: A total of 776 patients will be accrued for this study within 27 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

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

    • Local or metastatic failure after surgery and/or radiotherapy allowed
  • Phase II only:

    • At least one measurable lesion

      • 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

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

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 conduction defects, or ventricular arrhythmias requiring medication
  • No myocardial infarction within the 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 participation
  • No peripheral neuropathy
  • No condition (e.g., psychological, geographical) that would preclude study participation
  • No prior breast cancer or melanoma
  • No other prior malignancy within the past 5 years except carcinoma in situ, basal cell or squamous cell skin cancer, or other cancer that has been curatively treated surgically

PRIOR CONCURRENT THERAPY:

Biologic therapy:

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

Chemotherapy:

  • No prior antineoplastic chemotherapy, including intrapleural chemotherapy

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 drugs
  • No other concurrent cytotoxic anticancer therapy
  • No other investigational drugs during and for 30 days after study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00006229

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

Additional Information:
Publications:
Leighl NB, Shepherd F, Paz-Ares L, et al.: Randomized phase II-III study of matrix metalloproteinase inhibitor (MMPI) BMS-275291 in combination with paclitaxel (P) and carboplatin (C) in advanced non-small cell lung cancer (NSCLC): NCIC-CTG BR.18. [Abstract] J Clin Oncol 22 (Suppl 14): A-7038, 626s, 2004.
Bradbury PA, Twumasi-Ankrah P, Ding K, et al.: The impact of brain metastases on overall survival (OS) in National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) clinical trials (CT) in advanced non-small cell lung cancer (NSCLC). [Abstract] J Clin Oncol 27 (Suppl 15): A-8075, 2009.
Wheatley-Price P, Le Maître A, Ding K, et al.: The influence of sex on efficacy, toxicity and delivery of treatment in National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) non-small cell lung cancer (NSCLC) chemotherapy trials. [Abstract] J Clin Oncol 26 (Suppl 15): A-8054, 2008.
Hicks L, Cheung M, Hasan B, et al.: Venous thromboembolism and non-small cell lung cancer: a pooled analysis of National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) trials. [Abstract] Blood 110 (11): A-3995, 2007.

Responsible Party: NCIC Clinical Trials Group
ClinicalTrials.gov Identifier: NCT00006229     History of Changes
Other Study ID Numbers: BR18, CAN-NCIC-BR18, BMS-CA161-003, CDR0000068153
Study First Received: September 11, 2000
Last Updated: November 11, 2013
Health Authority: Canada: NCIC Clinical Trials Group

Keywords provided by NCIC Clinical Trials Group:
stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Paclitaxel
Carboplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 01, 2014