E7389 Versus Treatment of Physician's Choice in Patients With Locally Recurrent or Metastatic Breast Cancer

This study has been completed.
Sponsor:
Collaborator:
Eisai Limited
Information provided by (Responsible Party):
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT00388726
First received: October 13, 2006
Last updated: July 25, 2014
Last verified: July 2014
  Purpose

The purpose of this study is to compare Overall Survival (OS), Progression Free Survival (PFS), objective tumor response rate, duration of response, and safety in patients treated with E7389 versus the Treatment of Physician's Choice (TPC) in patients with locally recurrent or metastatic breast cancer.


Condition Intervention Phase
Breast Cancer
Drug: E7389
Drug: Physician's Choice
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The "EMBRACE" Trial: Eisai Metastatic Breast Cancer Study Assessing Physician's Choice Versus E7389. A Phase III Open-Label, Randomized, Parallel, Two-arm, Multi-center Study of E7389 Versus "Treatment of Physician's Choice" in Patients With Locally Recurrent, Metastatic Breast Cancer, Previously Treated With At Least Two and a Maximum of Five Prior Chemotherapy Regimens, Including an Anthracycline and a Taxane

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • Overall Survival [ Time Frame: From date of randomization until death from any cause ] [ Designated as safety issue: No ]
    Defined as the time from the date of randomization until the date of death from any cause.


Secondary Outcome Measures:
  • Progression-Free Survival. [ Time Frame: Until disease progression or death. ] [ Designated as safety issue: No ]
    Measured using Response Evaluation Criteria in Solid Tumors (RECIST) and defined as the time from the date of randomization until progressive disease or death from any cause in the absence of of progressive disease.

  • Best Overall Response [ Time Frame: Until Day 30 or every 3 months during Follow-up period for patients who complete study without PD. ] [ Designated as safety issue: No ]
    Measured by RECIST criteria and defined as the best response from the start of treatment until disease progression or recurrence. Lesions measured by computed tomography (CT) scan and magnetic resonance imaging (MRI). Objective response rate: complete response (CR-disappearance of all lesions)+ partial response (PR-30% decrease in lesion diameter), Progressive Disease (PD-20% increase in lesion diameter), stable disease (SD-neither shrinkage nor increase of lesions).

  • Duration of Response. [ Time Frame: From first documented CR or PR until disease progression or death. ] [ Designated as safety issue: No ]
    As measured by RECIST criteria and defined as the time from the first documented CR or PR until disease progression or death from any cause.

  • Safety Parameters: Adverse Events (AEs), Laboratory Parameters, Concomitant Medication, Electrocardiograms (ECGs), and Study Drug Exposure. [ Time Frame: AEs and conmeds - until study termination; lab tests - Day 1 and weekly until study termination; ECGs - Day 1 and at study termination. ] [ Designated as safety issue: Yes ]

Enrollment: 762
Study Start Date: October 2006
Study Completion Date: March 2010
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: E7389
1.4 mg/m^2 intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days.
Active Comparator: 2 Drug: Physician's Choice
Treatment of the Physician's Choice defined as any single agent chemotherapy, hormonal treatment or biological therapy approved for the treatment of cancer; or palliative treatment or radiotherapy, administered according to local practice, if applicable.

  Eligibility

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

Inclusion Criteria:

  1. Female patients with histologically or cytologically confirmed carcinoma of the breast.

    Every effort should be made to make paraffin embedded tissue or slides from the diagnostic biopsy or surgical specimen available for confirmation of diagnosis.

  2. Patients with locally recurrent or metastatic disease who have received at least two (and not more than five) prior chemotherapeutic regimens for breast cancer, at least two of which were administered for treatment of locally recurrent and/or metastatic disease.

    Prior therapy must be documented by the following criteria prior to entry onto study:

    • Regimens must have included an anthracycline (e.g., doxorubicin, epirubicin) and a taxane (e.g., paclitaxel, docetaxel) in any combination or order. Treatment with any of these agents is not required if they are contraindicated for a certain patient.
    • One or two of these regimens may have been administered as adjuvant and/or neoadjuvant therapy, but at least 2 must have been given for relapsed or metastatic disease.
    • Patients must have proved refractory to the most recent chemotherapy, documented by progression on or within six (6) months of therapy.
    • Patients with Human Epidermal Growth Factor 2 (HER2/neu) positive tumors may additionally have been treated with trastuzumab.
    • Patients may have additionally been treated with anti-hormonal therapy.
  3. Resolution of all chemotherapy or radiation-related toxicities to Grade 1 severity or lower, except for stable sensory neuropathy <= Grade 2 and alopecia.
  4. Age >= 18 years.
  5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2.
  6. Life expectancy of >= 3 months.
  7. Adequate renal function as evidenced by serum creatinine <= 2.0 mg/dL or calculated creatinine clearance >= 40 mL/min per the Cockcroft and Gault formula.
  8. Adequate bone marrow function as evidenced by absolute neutrophil count (ANC) >= 1.5 x 10^9/L, hemoglobin >= 10.0 g/dL (a hemoglobin <10.0 g/dL is acceptable if it is corrected by growth factor or transfusion), and platelet count >= 100 x 10^9/L.
  9. Adequate liver function as evidenced by bilirubin <= 1.5 times the upper limits of normal (ULN) and alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) <= 3 x ULN (in the case of liver metastases <= 5 x ULN), unless there are bone metastases, in which case liver specific alkaline phosphatase must be separated from the total and used to assess the liver function instead of the total alkaline phosphatase. In case alkaline phosphatase is >3 x ULN (in absence of liver metastases) or > 5 x ULN (in presence of liver metastases) AND patient is known to have bone metastases, the liver specific alkaline phosphatase must be separated from the total and used to assess the liver function instead of the total alkaline phosphatase.
  10. Patients willing and able to comply with the study protocol for the duration of the study.
  11. Written informed consent prior to any study-specific screening procedures with the understanding that the patient may withdraw consent at any time without prejudice.

EXCLUSION CRITERIA

  1. Patients who have received any of the following treatments within the specified period before E7389 or TPC treatment start:

    • chemotherapy, radiation, trastuzumab or hormonal therapy within three weeks.
    • any investigational drug within four weeks.
  2. Radiation therapy encompassing > 30% of marrow.
  3. Prior treatment with mitomycin C or nitrosourea.
  4. Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen.
  5. Patients with brain or subdural metastases are not eligible, unless they have completed local therapy and have discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment in this study. Any signs (e.g., radiologic) and/or symptoms of brain metastases must be stable for at least 4 weeks before starting study treatment; radiographic stability should be determined by comparing a contrast-enhanced computed tomography or magnetic resonance imaging brain scan performed during screening to a prior scan performed at least 4 weeks earlier.
  6. Patients with meningeal carcinomatosis.
  7. Patients who are receiving anti-coagulant therapy with warfarin or related compounds, other than for line patency, and cannot be changed to heparin-based therapy if randomized to E7389 are not eligible. If a patient is to continue on mini-dose warfarin, then the prothrombin time (PT) or international normalized ratio (INR) must be closely monitored.
  8. Women who are pregnant or breast-feeding; women of childbearing potential with either a positive pregnancy test at screening or no pregnancy test; women of childbearing potential unless (1) surgically sterile or (2) using adequate measures of contraception in the opinion of the Investigator. Perimenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.
  9. Severe/uncontrolled intercurrent illness/infection.
  10. Significant cardiovascular impairment (history of congestive heart failure > New York Heart Association grade II, unstable angina or myocardial infarction within the past six months, or serious cardiac arrhythmia).
  11. Patients with organ allografts requiring immunosuppression.
  12. Patients with known positive HIV status.
  13. Patients who have had a prior malignancy, other than previous breast cancer, carcinoma in situ of the cervix, or non-melanoma skin cancer, unless the prior malignancy was diagnosed and definitively treated >= 5 years previously with no subsequent evidence of recurrence.
  14. Patients with pre-existing neuropathy > Grade 2.
  15. Patients with a hypersensitivity to halichondrin B and/or halichondrin B chemical derivative.
  16. Patients who participated in a prior E7389 clinical trial whether or not E7389 was received.
  17. Patients with other significant disease or disorders that, in the Investigator's opinion, would exclude the patient from the 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: NCT00388726

  Hide Study Locations
Locations
United States, Alabama
US Oncology St. Vincent's Hospital - Bruno Cancer Center
Birmingham, Alabama, United States
United States, California
Bellflower Satellite
Bellflower, California, United States
Research Center
Gilroy, California, United States, 95020
United States, Colorado
US Oncology
Denver, Colorado, United States
United States, Florida
Florida Cancer Research Institute
Davie, Florida, United States
Innovative Medical Research of South Florida, Inc.
Miami, Florida, United States, 33179
United States, Georgia
Peachtree Hematology/Oncology Consultants, PC
Atlanta, Georgia, United States
United States, Illinois
US Oncology
Niles, Illinois, United States
United States, Indiana
US Oncology
Indianapolis, Indiana, United States
United States, Iowa
University of Iowa Hospital and Clinic
Iowa City, Iowa, United States
United States, Louisiana
Hematology Oncology Clinic
Baton Rouge, Louisiana, United States
United States, Michigan
Oncology Care Associates, P.L.L.C.
St. Joseph, Michigan, United States
United States, Missouri
US Oncology
Columbia, Missouri, United States
United States, Montana
Montana Cancer Specialists
Missoula, Montana, United States, 59820
United States, Nevada
US Oncology
Las Vegas, Nevada, United States
United States, New York
US Oncology
Albany, New York, United States
North Shore Hematology/Oncology Associates
East Setauket, New York, United States
Weill Cornell Breast Cancer Center
New York, New York, United States
United States, North Carolina
Carolina Hematology Oncology Associates
Charlotte, North Carolina, United States
US Oncology
Raleigh, North Carolina, United States
United States, Oregon
US Oncology
Eugene, Oregon, United States
St. Vincent Medical Center
Portland, Oregon, United States
United States, Texas
US Oncology
Bedford, Texas, United States
US Oncology
Dallas, Texas, United States
US Oncology
Houston, Texas, United States
US Oncology
McAllen, Texas, United States
US Oncology
Midland, Texas, United States
US Oncology
Tyler, Texas, United States
United States, Washington
US Oncology
Spokane, Washington, United States
Northwest Medical Specialists
Tacoma, Washington, United States, 98401
US Oncology
Vancouver, Washington, United States
US Oncology
Yakima, Washington, United States
Argentina
Instituto Oncologico "Las Heras"
Bahia Blanca, Buenos Aires, Argentina, B8000ILF
Hospital Britanico
C.a.b.a, Buenos Aires, Argentina, C1280AEB
Instituto FIDES especialidades Medicas
La Plata, Buenos Aires, Argentina, 1900
Breast Clinica de la Mama
La Plata, Buenos Aires, Argentina
CITEM
Quilmes, Buenos Aires, Argentina
CER Instituto Medico
Quilmes Oeste, Buenos Aires, Argentina
Instituto CAICI
Rosario, Pcia. Santa Fe, Argentina, S2000PBJ
Centro Medico San Roque
Tucuman, San Miguel de Tucuman, Argentina
Hosptial Interzonal General de Mar del Plata
Buenos Aires, Argentina, 7600
Clinica Universitaria Privada Reina Fabiola
Cordoba, Argentina
Sanatorio Frances
Cordoba, Argentina
Instituto de Oncologia y Especialidades Medicas
Rosario Santa Fe, Argentina, 2000
Clinica Especializada ISIS
Santa Fe, Argentina, S3000FFU
Australia, Queensland
The Queen Elizabeth Hospital
Southport, Queensland, Australia, 4215
Australia, South Australia
Servicio De Oncologia
Woodville South, South Australia, Australia, 5011
Australia
Maroondah Breast Clinic
Melbourne, Australia, 3135
Mater Medical Centre
North Sydney, Australia, 2060
Royal Perth Hospital, Department of Medical Oncology
Perth, Australia, 6000
Mount Hospital
Perth, Australia, 6000
Austria
Medizinische Universitatsklinik Graz
Graz Steiermark, Austria, 8036
Salzburger Landeskliniken Universitatsklinik fur Innere medizin III
Salzburg, Austria, 5020
Belgium
Institut Jules Bordet
Brussels, Belgium, 1000
Cliniques Universitaires Saint-Luc
Bruxelles, Belgium, 1200
Centre Hospitalier Notre-Dame - Reine Fabiola
Charleroi, Belgium, 6000
UZ Gent
Gent, Belgium, B-9000
AZ Groeninge, Campus Maria's Voorzienigheid
Kortrijk, Belgium, 8500
Brazil
Centro Regional Integrado de Oncologia-CRIO
Fortaleza, CE, Brazil
Centro de Pesquisas e Estudios do Centro Goiano
Giana, GO, Brazil
Hospital Erasto Gaertner
Curitiba, PA, Brazil
Instituto Nacional do Cancer-Unidade III (INCA III)
Rio De Janiero, RJ, Brazil
CPO-Centro de Pesquisas em Oncologia
Porto Alegre, RS, Brazil
CEPHO-Centro de Estudos e Pesquisa de Hematologia e oncologia
Santo Andre, SP, Brazil
Santo Andre Diagnosticos e Tratamentos
Santo Andre, SP, Brazil
Clinica de Oncologia Medica
Sao Paulo, SP, Brazil
Hospital Amaral Carvalho
Vila Assis, SP, Brazil
Canada, Ontario
The Ottawa Hospital Regional Cancer Center
Ottawa, Ontario, Canada
Sunnybrook Odette Cancer Centre
Toronto, Ontario, Canada, M4N 3M5
Canada, Quebec
McGill University Health Centre, Department of Oncology, Gerald Bronfman Center
Montreal, Quebec, Canada
Croatia
Clinical Hospital Osijek
Osijek, Croatia, 31000
University Hospital Center Zagreb
Zagreb, Croatia, 1000
University Hospital for Tumors Zagreb
Zagreb, Croatia, 1000
Czech Republic
Masaryk Memorial Cancer Institute
Brno, Czech Republic, 656 53
Hospital Jihlava
Jihlava, Czech Republic, 58633
General Faculty Hospital Prague
Prague, Czech Republic, 128 08
Fakultni Thomayerova Nemocnice
Prague, Czech Republic, 14059
Ustav radia ni onkologie 1. LF UK a FNB
Praha, Czech Republic, 18000
Clinic of Radiotherapy and Oncology
Praha 10, Czech Republic, 100 34
France
Centre Paul Papin
Agners Cedex 01, France, 46033
Hopital Jean Minjoz
Besancon, France, 25030
Polyclinique Boredaux Nord Aquitaine
Bordeaux, France, 33300
Centre Francois Baclesse Caen
Caen Cedex 05, France, 14076
Centre Jean Perrin - CRLC
Clermont-Ferrand Cedex 01, France, 63011
Centre Georges-Francois Lecierc
Dijon Cedex, France, 21079
Hopital Edourad Herriot
Lyon, France, 69008
Institut Curie
Paris, France, 75005
Clinique Armoricaine de Radiologie
Saint Brieuc Cedex, France, 22015
Hopital Bretonneau
Tours Cedex, France, 37044
Hungary
Semmelweis Medical University, III. Dep. of Internal Med.
Budapest, Hungary, 1125
Debrecen Medical University, Department of Oncology
Debrecen, Hungary, 4012
University of Pecs
Pecs, Hungary, 7200
Markusovszky Teaching Hospital, Dept. of Oncoradiology, Sec. Med. Oncology
Szombathely, Hungary, 9700
Italy
Azienda Ospedaliera Careggi
Firenze (FI), Italy, 50139
Ospedale San Martino
Genova, Italy, 16132
Ospedale "Vito Fazzi" - Lecce
Lecce (LE), Italy, 73100
Istituto Scientifico San Raffaele
Milano, Italy, 20132
Ospedale San Filippo Neri
Roma, Italy, 00135
Istituto Clinico Humanitas
Rozzano, Italy, 20089
UO di Oncologia
Sora, Italy, 03039
Poland
Akademickie Centrum Kliniczne Szpital Akademii Medycznej w
Gdansk, Poland, 80952
Szpital Morski im PCK w Gdyni Gdynskie Centrum Onkologii
Gdynia, Poland, 81519
Centrum Onkologii Instytut M. Sklodowskiej Curie w Warszawie Oddzial Gilwice
Gilwice, Poland, 44101
Centrum Onkologii Instytut M Sklodowskiej Curie, Oddzial w Krakowie
Krakow, Poland, 31-115
Szpital Kiniczny Przemienienia Panskiego Uniwersyteu Medycznego im Karola Marcinkowskiego w Poznaniu
Poznan, Poland, 61878
Zachodniopomorski e Centrum
Szczecin, Poland, 71-730
Centrum Onkologii Instytut im M. Sklodowskiej Curie w Warszawie
Warszawa, Poland, 02781
Russian Federation
Republic Clinical Oncology Dispensary
Izhervsk Udmurtia, Russian Federation, 426009
Kazan State Medical University
Kazan, Russian Federation, 420012
Krasnodar Territory Clinical Oncology Center
Krasnodar, Russian Federation, 350040
Burdenko Main Military Hospital
Moscow, Russian Federation, 105229
Nizhniy Novgorod City Oncology Center
Nizhny Novgorod, Russian Federation, 603081
City Clinical Hospital #1
Novosibirisk, Russian Federation, 630047
Republican Oncology Center
Petrozavodsk, Russian Federation, 185007
State Institution of Healthcare Stavropol Region clinical Oncology dispensary
Pyatigorsk, Russian Federation
St Petersburg City Oncology Center
St Petersburg, Russian Federation, 197022
Pavlov Medical University
St. Petersburg, Russian Federation, 190722
NN Petrov Research Institute of Oncology
St. Petersburg, Russian Federation, 197758
Tomsk Regional Oncology Dispensary
Tomsk, Russian Federation, 634050
GUZ YO Regional Clinical Oncology Hospital
Yaroslavl, Russian Federation, 150054
South Africa
Panorama Medical Centre
Panorama, Cape Town, South Africa, 7500
Eastern Cape Oncology Centre, GVI, St Georges Hospital
Port Elizabeth, Eastern Cape, South Africa, 6001
Sandton Oncology Centre
Johannesburg, South Africa, 2057
Pretoria Academic Hospital
Pretoria, South Africa, 0001
Spain
Hospital Mutua de Terrassa
Barcelona, Spain, E-08221
Hospital Vall d Hebron
Barcelona, Spain, 08035
Hospital Universitario de Girona Dr. Josep Trueta
Gerona, Spain, 17007
Complejo Hospitalario de Jaen
Jaen, Spain, E-23007
Hospital Unversitatio de Salamanca
Salamanca, Spain, E37007
Hospital Universitario de Canarias
Santa Cruz de Tenerife, Spain, E-38320
Hospital General Virgen del Rocio
Sevilla, Spain, E-41013
Hospital Clinico de Zaragoza
Zanagoza, Spain, 50009
Switzerland
Kantonsspital Aarau
Aarau, Switzerland, 5001
Inselspital Bern
Bern Bern, Switzerland, 3010
Kantonsspital Oncology Haematology
St. Gallen, Switzerland, CH9007
Spital Thun-Simmental AG
Thun, Switzerland, 3600
Kantonsspital Winterhur
Winterhur, Switzerland, CH-8401
Sponsors and Collaborators
Eisai Inc.
Eisai Limited
Investigators
Study Director: Jantien Wanders, M.D. Eisai Limited
  More Information

No publications provided by Eisai Inc.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT00388726     History of Changes
Other Study ID Numbers: E7389-G000-305, 2006-001949-34
Study First Received: October 13, 2006
Results First Received: December 22, 2011
Last Updated: July 25, 2014
Health Authority: United States: Food and Drug Administration
European Union: European Medicines Agency

Keywords provided by Eisai Inc.:
Locally recurrent breast cancer
metastatic breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on September 22, 2014