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

• Sponsor: NCIC Clinical Trials Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00006229
• Collaborator: (none)
• Enrollment: 774
• Locations: 69
• Arms: 2
• Actual Duration (Months): 106.3
• Patients Per Site: 11.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer	Drug: carboplatin; Drug: paclitaxel; Drug: rebimastat	Phase 2/Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 774 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, 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
• Actual Study Start Date: Apr 4, 2000
• Actual Primary Completion Date: Dec 10, 2003
• Actual Study Completion Date: Feb 10, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BMS-275291	Drug: carboplatin; Drug: paclitaxel; Drug: rebimastat
Placebo Comparator: Placebo	Drug: carboplatin; Drug: paclitaxel

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham Comprehensive Cancer Center	Birmingham	Alabama	United States	35294-3300
2	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
3	Scripps Clinic	La Jolla	California	United States	92037
4	Central Georgia Hematology Oncology, P.C.	Macon	Georgia	United States	31201
5	Queen's Medical Center	Honolulu	Hawaii	United States	96813
6	Carle Cancer Center	Urbana	Illinois	United States	61801
7	Lahey Clinic - Burlington	Burlington	Massachusetts	United States	01805
8	Creighton University Cancer Center	Omaha	Nebraska	United States	68131-2197
9	Duke University Medical Center	Durham	North Carolina	United States	27710
10	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73190
11	Erlanger Health Systems	Chattanooga	Tennessee	United States	37403
12	Memorial Hospital Cancer Center - Chattanooga	Chattanooga	Tennessee	United States	37404
13	Williamson Medical Center	Franklin	Tennessee	United States	37068-1600
14	Jackson-Madison County General Hospital	Jackson	Tennessee	United States	38301
15	Baptist Regional Cancer Center - Knoxville	Knoxville	Tennessee	United States	37901
16	Saint Thomas Hospital	Nashville	Tennessee	United States	37205
17	Meharry Medical College	Nashville	Tennessee	United States	37208-3599
18	Division of Medical Oncology - Vanderbilt	Nashville	Tennessee	United States	37232-5536
19	AKH Vienna	Vienna (Wien)		Austria	A-1090
20	Allgemeines Krankenhaus der Stadt Wien	Vienna (Wien)		Austria	A-1090
21	Universiteit Gent	Gent		Belgium	B-9000
22	Centre Hospitalier Regional de la Citadelle	Liege (Luik)		Belgium	4000
23	Algemeen Ziekenhuis Sint-Augustinus	Wilrijk		Belgium	2610
24	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
25	CancerCare Manitoba	Winnipeg	Manitoba	Canada	R3E 0V9
26	Nova Scotia Cancer Centre	Halifax	Nova Scotia	Canada	B3H 1V7
27	Royal Victoria Hospital, Barrie	Barrie	Ontario	Canada	L4M 6M2
28	Cancer Care Ontario-Hamilton Regional Cancer Centre	Hamilton	Ontario	Canada	L8V 5C2
29	Ottawa Regional Cancer Centre	Ottawa	Ontario	Canada	K1H 1C4
30	Peterborough Oncology Clinic	Peterborough	Ontario	Canada	K9H 7B6
31	Algoma District Medical Group	Sault Sainte Marie	Ontario	Canada	P6B 1Y5
32	Hotel Dieu Health Sciences Hospital - Niagara	St. Catharines	Ontario	Canada	L2R 5K3
33	Toronto Sunnybrook Regional Cancer Centre	Toronto	Ontario	Canada	M4N 3M5
34	Mount Sinai Hospital - Toronto	Toronto	Ontario	Canada	M5G 1X5
35	Toronto General Hospital	Toronto	Ontario	Canada	M5G 2C4
36	Saint Joseph's Health Centre - Toronto	Toronto	Ontario	Canada	M6R 1B5
37	Humber River Regional Hospital	Weston	Ontario	Canada	M9N 1N8
38	Cancer Care Ontario - Windsor Regional Cancer Centre	Windsor	Ontario	Canada	N8W 2X3
39	Allan Blair Cancer Centre	Regina	Saskatchewan	Canada	S4T 7T1
40	Saskatoon Cancer Centre	Saskatoon	Saskatchewan	Canada	S7N 4H4
41	Helsinki University Central Hospital	Helsinki		Finland	FIN-0-0029
42	CHR de Besancon - Hopital Jean Minjoz	Besancon		France	25030
43	Hopital Avicenne	Bobigny		France	93009
44	CHR de Grenoble - La Tronche	Grenoble		France	38043
45	CRLCC Nantes - Atlantique	Nantes-Saint Herblain		France	44805
46	Hopital de Neuhof	Strasbourg		France	67091
47	Institut Claudius Regaud	Toulouse		France	31052
48	Centre Hospitalier Universitaire Bretonneau de Tours	Tours		France	37044
49	Stadisches Krankenhaus Martha Maria Halle-Dolau	Halle		Germany	06120
50	Allgemeines Krankenhaus	Hamburg		Germany	DOH-2-1075
51	Lungenklinik Hemer	Hemer		Germany	D-58675
52	Marienhospital/Ruhr University Bochum	Herne		Germany	DOH-4-4625
53	Klinikum Rechts Der Isar/Technische Universitaet Muenchen	Munich (Muenchen)		Germany	D-81675
54	Oncologia Medica - Perugia	Perugia		Italy	06122
55	Ospedale San Filippo Neri	Rome		Italy	00135
56	Ospedale Carlo Forlanini	Rome		Italy	00149
57	Istituto Clinico Humanitas	Rozzano (MI)		Italy	20089
58	Ospedale Civile San Giovanni e Paolo	Venezia		Italy	30122
59	Academisch Ziekenhuis Maastricht	Maastricht		Netherlands	6202 AZ
60	Medical University of Gdansk	Gdansk		Poland	80-211
61	Centro Hospitalar de Vila Nova de Gaia	Vila Nova de Gaia		Portugal	4434-502
62	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
63	Hospital Universitario Marques de Valdecilla	Santander		Spain	39008
64	Servicio De Oncologia	Valencia		Spain	46017
65	Kantonspital Aarau	Aarau		Switzerland	5001
66	Inselspital, Bern	Bern		Switzerland	CH-3010
67	Universitaetsspital	Zurich		Switzerland	CH-8091
68	Charing Cross Hospital	London	England	United Kingdom	W6 8RF
69	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

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• 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.
• Hicks LK, Cheung MC, Ding K, Hasan B, Seymour L, Le Maître A, Leighl NB, Shepherd FA. Venous thromboembolism and nonsmall cell lung cancer: a pooled analysis of National Cancer Institute of Canada Clinical Trials Group trials. Cancer. 2009 Dec 1;115(23):5516-25. doi: 10.1002/cncr.24596.
• Wheatley-Price P, Le Maître A, Ding K, Leighl N, Hirsh V, Seymour L, Bezjak A, Shepherd FA; NCIC Clinical Trials Group. The influence of sex on efficacy, adverse events, quality of life, and delivery of treatment in National Cancer Institute of Canada Clinical Trials Group non-small cell lung cancer chemotherapy trials. J Thorac Oncol. 2010 May;5(5):640-8. doi: 10.1097/JTO.0b013e3181d40a1b.

• Responsible Party: NCIC Clinical Trials Group
• ClinicalTrials.gov Identifier: NCT00006229
• Other Study ID Numbers: BR18; CAN-NCIC-BR18; BMS-CA161-003; CDR0000068153
• First Posted: Jul 25, 2003
• Last Update Posted: Apr 6, 2020
• Last Verified: Apr 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• 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; Paclitaxel; Carboplatin

Study Results

No Results Posted as of Apr 6, 2020