Clinical trial NCT00006229: Paclitaxel + Carboplatin With/ut BMS-275291 in Advanced or Metastatic Non-small Cell Lung Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Lung Cancer
Keywords: stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
First posted: 2003-07-25
Enrollment: 774
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Comprehensive Cancer Center
state: Alabama
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: La Jolla
country: United States
facility: Scripps Clinic
state: California
city: Macon
country: United States
facility: Central Georgia Hematology Oncology, P.C.
state: Georgia
city: Honolulu
country: United States
facility: Queen's Medical Center
state: Hawaii
city: Urbana
country: United States
facility: Carle Cancer Center
state: Illinois
city: Burlington
country: United States
facility: Lahey Clinic - Burlington
state: Massachusetts
city: Omaha
country: United States
facility: Creighton University Cancer Center
state: Nebraska
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Chattanooga
country: United States
facility: Erlanger Health Systems
state: Tennessee
city: Chattanooga
country: United States
facility: Memorial Hospital Cancer Center - Chattanooga
state: Tennessee
city: Franklin
country: United States
facility: Williamson Medical Center
state: Tennessee
city: Jackson
country: United States
facility: Jackson-Madison County General Hospital
state: Tennessee
city: Knoxville
country: United States
facility: Baptist Regional Cancer Center - Knoxville
state: Tennessee
city: Nashville
country: United States
facility: Saint Thomas Hospital
state: Tennessee
city: Nashville
country: United States
facility: Meharry Medical College
state: Tennessee
city: Nashville
country: United States
facility: Division of Medical Oncology - Vanderbilt
state: Tennessee
city: Vienna (Wien)
country: Austria
facility: AKH Vienna
city: Vienna (Wien)
country: Austria
facility: Allgemeines Krankenhaus der Stadt Wien
city: Gent
country: Belgium
facility: Universiteit Gent
city: Liege (Luik)
country: Belgium
facility: Centre Hospitalier Regional de la Citadelle
city: Wilrijk
country: Belgium
facility: Algemeen Ziekenhuis Sint-Augustinus
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Halifax
country: Canada
facility: Nova Scotia Cancer Centre
state: Nova Scotia
city: Barrie
country: Canada
facility: Royal Victoria Hospital, Barrie
state: Ontario
city: Hamilton
country: Canada
facility: Cancer Care Ontario-Hamilton Regional Cancer Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Regional Cancer Centre
state: Ontario
city: Peterborough
country: Canada
facility: Peterborough Oncology Clinic
state: Ontario
city: Sault Sainte Marie
country: Canada
facility: Algoma District Medical Group
state: Ontario
city: St. Catharines
country: Canada
facility: Hotel Dieu Health Sciences Hospital - Niagara
state: Ontario
city: Toronto
country: Canada
facility: Toronto Sunnybrook Regional Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital - Toronto
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Toronto
country: Canada
facility: Saint Joseph's Health Centre - Toronto
state: Ontario
city: Weston
country: Canada
facility: Humber River Regional Hospital
state: Ontario
city: Windsor
country: Canada
facility: Cancer Care Ontario - Windsor Regional Cancer Centre
state: Ontario
city: Regina
country: Canada
facility: Allan Blair Cancer Centre
state: Saskatchewan
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre
state: Saskatchewan
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital
city: Besancon
country: France
facility: CHR de Besancon - Hopital Jean Minjoz
city: Bobigny
country: France
facility: Hopital Avicenne
city: Grenoble
country: France
facility: CHR de Grenoble - La Tronche
city: Nantes-Saint Herblain
country: France
facility: CRLCC Nantes - Atlantique
city: Strasbourg
country: France
facility: Hopital de Neuhof
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Tours
country: France
facility: Centre Hospitalier Universitaire Bretonneau de Tours
city: Halle
country: Germany
facility: Stadisches Krankenhaus Martha Maria Halle-Dolau
city: Hamburg
country: Germany
facility: Allgemeines Krankenhaus
city: Hemer
country: Germany
facility: Lungenklinik Hemer
city: Herne
country: Germany
facility: Marienhospital/Ruhr University Bochum
city: Munich (Muenchen)
country: Germany
facility: Klinikum Rechts Der Isar/Technische Universitaet Muenchen
city: Perugia
country: Italy
facility: Oncologia Medica - Perugia
city: Rome
country: Italy
facility: Ospedale San Filippo Neri
city: Rome
country: Italy
facility: Ospedale Carlo Forlanini
city: Rozzano (MI)
country: Italy
facility: Istituto Clinico Humanitas
city: Venezia
country: Italy
facility: Ospedale Civile San Giovanni e Paolo
city: Maastricht
country: Netherlands
facility: Academisch Ziekenhuis Maastricht
city: Gdansk
country: Poland
facility: Medical University of Gdansk
city: Vila Nova de Gaia
country: Portugal
facility: Centro Hospitalar de Vila Nova de Gaia
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
city: Valencia
country: Spain
facility: Servicio De Oncologia
city: Aarau
country: Switzerland
facility: Kantonspital Aarau
city: Bern
country: Switzerland
facility: Inselspital, Bern
city: Zurich
country: Switzerland
facility: Universitaetsspital
city: London
country: United Kingdom
facility: Charing Cross Hospital
state: England
city: London
country: United Kingdom
facility: Chelsea Westminster Hospital
Study officials:
affiliation: Cross Cancer Institute at University of Alberta
name: Michael Smylie, MD, MB, ChB
role: STUDY_CHAIR
References:
citation: 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.
citation: Asmis TR, Ding K, Seymour L, Shepherd FA, Leighl NB, Winton TL, Whitehead M, Spaans JN, Graham BC, Goss GD; National Cancer Institute of Canada Clinical Trials Group. Age and comorbidity as independent prognostic factors in the treatment of non small-cell lung cancer: a review of National Cancer Institute of Canada Clinical Trials Group trials. J Clin Oncol. 2008 Jan 1;26(1):54-9. doi: 10.1200/JCO.2007.12.8322.
citation: 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.
citation: 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.
citation: Douillard JY, Peschel C, Shepherd F, Paz-Ares L, Arnold A, Davis M, Tonato M, Smylie M, Tu D, Voi M, Humphrey J, Ottaway J, Young K, Vreckem AV, Seymour L. Randomized phase II feasibility study of combining the matrix metalloproteinase inhibitor BMS-275291 with paclitaxel plus carboplatin in advanced non-small cell lung cancer. Lung Cancer. 2004 Dec;46(3):361-8. doi: 10.1016/j.lungcan.2004.05.009.
citation: Leighl NB, Paz-Ares L, Douillard JY, Peschel C, Arnold A, Depierre A, Santoro A, Betticher DC, Gatzemeier U, Jassem J, Crawford J, Tu D, Bezjak A, Humphrey JS, Voi M, Galbraith S, Hann K, Seymour L, Shepherd FA. Randomized phase III study of matrix metalloproteinase inhibitor BMS-275291 in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: National Cancer Institute of Canada-Clinical Trials Group Study BR.18. J Clin Oncol. 2005 Apr 20;23(12):2831-9. doi: 10.1200/JCO.2005.04.044.
citation: 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.