Paclitaxel + Carboplatin With/ut BMS-275291 in Advanced or Metastatic Non-small Cell Lung Cancer

Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00006229
• Other study ID #: BR18
• Secondary ID: CAN-NCIC-BR18BMS
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: April 4, 2000
• Est. completion date: February 10, 2009

Study information

• Verified date: April 2020
• Source: Canadian Cancer Trials Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 774
• Est. completion date: February 10, 2009
• Est. primary completion date: December 10, 2003
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms

Intervention

Drug:
• carboplatin

• paclitaxel

• rebimastat

Locations

Country	Name	City	State
Austria	AKH Vienna	Vienna (Wien)
Austria	Allgemeines Krankenhaus der Stadt Wien	Vienna (Wien)
Belgium	Universiteit Gent	Gent
Belgium	Centre Hospitalier Regional de la Citadelle	Liege (Luik)
Belgium	Algemeen Ziekenhuis Sint-Augustinus	Wilrijk
Canada	Royal Victoria Hospital, Barrie	Barrie	Ontario
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Nova Scotia Cancer Centre	Halifax	Nova Scotia
Canada	Cancer Care Ontario-Hamilton Regional Cancer Centre	Hamilton	Ontario
Canada	Ottawa Regional Cancer Centre	Ottawa	Ontario
Canada	Peterborough Oncology Clinic	Peterborough	Ontario
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	Algoma District Medical Group	Sault Sainte Marie	Ontario
Canada	Hotel Dieu Health Sciences Hospital - Niagara	St. Catharines	Ontario
Canada	Mount Sinai Hospital - Toronto	Toronto	Ontario
Canada	Saint Joseph's Health Centre - Toronto	Toronto	Ontario
Canada	Toronto General Hospital	Toronto	Ontario
Canada	Toronto Sunnybrook Regional Cancer Centre	Toronto	Ontario
Canada	Humber River Regional Hospital	Weston	Ontario
Canada	Cancer Care Ontario - Windsor Regional Cancer Centre	Windsor	Ontario
Canada	CancerCare Manitoba	Winnipeg	Manitoba
Finland	Helsinki University Central Hospital	Helsinki
France	CHR de Besancon - Hopital Jean Minjoz	Besancon
France	Hopital Avicenne	Bobigny
France	CHR de Grenoble - La Tronche	Grenoble
France	CRLCC Nantes - Atlantique	Nantes-Saint Herblain
France	Hopital de Neuhof	Strasbourg
France	Institut Claudius Regaud	Toulouse
France	Centre Hospitalier Universitaire Bretonneau de Tours	Tours
Germany	Stadisches Krankenhaus Martha Maria Halle-Dolau	Halle
Germany	Allgemeines Krankenhaus	Hamburg
Germany	Lungenklinik Hemer	Hemer
Germany	Marienhospital/Ruhr University Bochum	Herne
Germany	Klinikum Rechts Der Isar/Technische Universitaet Muenchen	Munich (Muenchen)
Italy	Oncologia Medica - Perugia	Perugia
Italy	Ospedale Carlo Forlanini	Rome
Italy	Ospedale San Filippo Neri	Rome
Italy	Istituto Clinico Humanitas	Rozzano (MI)
Italy	Ospedale Civile San Giovanni e Paolo	Venezia
Netherlands	Academisch Ziekenhuis Maastricht	Maastricht
Poland	Medical University of Gdansk	Gdansk
Portugal	Centro Hospitalar de Vila Nova de Gaia	Vila Nova de Gaia
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Marques de Valdecilla	Santander
Spain	Servicio De Oncologia	Valencia
Switzerland	Kantonspital Aarau	Aarau
Switzerland	Inselspital, Bern	Bern
Switzerland	Universitaetsspital	Zurich
United Kingdom	Charing Cross Hospital	London	England
United Kingdom	Chelsea Westminster Hospital	London
United States	University of Alabama at Birmingham Comprehensive Cancer Center	Birmingham	Alabama
United States	Lahey Clinic - Burlington	Burlington	Massachusetts
United States	Erlanger Health Systems	Chattanooga	Tennessee
United States	Memorial Hospital Cancer Center - Chattanooga	Chattanooga	Tennessee
United States	Duke University Medical Center	Durham	North Carolina
United States	Williamson Medical Center	Franklin	Tennessee
United States	Queen's Medical Center	Honolulu	Hawaii
United States	Jackson-Madison County General Hospital	Jackson	Tennessee
United States	Baptist Regional Cancer Center - Knoxville	Knoxville	Tennessee
United States	Scripps Clinic	La Jolla	California
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Central Georgia Hematology Oncology, P.C.	Macon	Georgia
United States	Division of Medical Oncology - Vanderbilt	Nashville	Tennessee
United States	Meharry Medical College	Nashville	Tennessee
United States	Saint Thomas Hospital	Nashville	Tennessee
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Creighton University Cancer Center	Omaha	Nebraska
United States	Carle Cancer Center	Urbana	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
NCIC Clinical Trials Group

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Canada,  Finland,  France,  Germany,  Italy,  Netherlands,  Poland,  Portugal,  Spain,  Switzerland,  United Kingdom, 

References & Publications (7)

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. — View 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.

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. — View 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.

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 metall — View 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. [Abstra

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.