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

Phase 3

Completed

Conditions: Breast Cancer

Interventions: Drug: Physician's Choice
Drug: E7389

Registration Number: NCT00388726

Lead Sponsor: Eisai Inc.

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 762

Inclusion Criteria

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.
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.
Resolution of all chemotherapy or radiation-related toxicities to Grade 1 severity or lower, except for stable sensory neuropathy <= Grade 2 and alopecia.
Age >= 18 years.
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2.
Life expectancy of >= 3 months.
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.
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.
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.
Patients willing and able to comply with the study protocol for the duration of the study.
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

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.
Radiation therapy encompassing > 30% of marrow.
Prior treatment with mitomycin C or nitrosourea.
Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen.
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.
Patients with meningeal carcinomatosis.
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.
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.
Severe/uncontrolled intercurrent illness/infection.
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).
Patients with organ allografts requiring immunosuppression.
Patients with known positive HIV status.
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.
Patients with pre-existing neuropathy > Grade 2.
Patients with a hypersensitivity to halichondrin B and/or halichondrin B chemical derivative.
Patients who participated in a prior E7389 clinical trial whether or not E7389 was received.
Patients with other significant disease or disorders that, in the Investigator's opinion, would exclude the patient from the study.

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2	Physician's Choice	-
1	E7389	-

Primary Outcome Measures

Name	Time	Method
Overall Survival	From date of randomization until death from any cause	Defined as the time from the date of randomization until the date of death from any cause.

Secondary Outcome Measures

Name	Time	Method
Duration of Response.	From first documented CR or PR until disease progression or death.	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.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	From start of study drug administration up to 30 days after the last dose of study drug (approximately up to 42 months)
Progression-Free Survival.	Until disease progression or death.	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	Until Day 30 or every 3 months during Follow-up period for patients who complete study without PD.	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).

Trial Locations

Locations (121): Montana Cancer Specialists
🇺🇸
Missoula, Montana, United States
Bellflower Satellite
🇺🇸
Bellflower, California, United States
Weill Cornell Breast Cancer Center
🇺🇸
New York, New York, United States
Instituto CAICI
🇦🇷
Rosario, Pcia. Santa Fe, Argentina
Sanatorio Frances
🇦🇷
Cordoba, Argentina
Royal Perth Hospital, Department of Medical Oncology
🇦🇺
Perth, Australia
Salzburger Landeskliniken Universitatsklinik fur Innere medizin III
🇦🇹
Salzburg, Austria
Institut Jules Bordet
🇧🇪
Brussels, Belgium
Centre Hospitalier Notre-Dame - Reine Fabiola
🇧🇪
Charleroi, Belgium
Sunnybrook Odette Cancer Centre
🇨🇦
Toronto, Ontario, Canada
Masaryk Memorial Cancer Institute
🇨🇿
Brno, Czechia
Ospedale San Filippo Neri
🇮🇹
Roma, Italy
Akademickie Centrum Kliniczne Szpital Akademii Medycznej w
🇵🇱
Gdansk, Poland
Zachodniopomorski e Centrum
🇵🇱
Szczecin, Poland
St Petersburg City Oncology Center
🇷🇺
St Petersburg, Russian Federation
Hospital General Virgen del Rocio
🇪🇸
Sevilla, Spain
Hospital Clinico de Zaragoza
🇪🇸
Zanagoza, Spain
Kantonsspital Aarau
🇨🇭
Aarau, Switzerland
Kantonsspital Winterhur
🇨🇭
Winterhur, Switzerland
Innovative Medical Research of South Florida, Inc.
🇺🇸
Miami, Florida, United States
Medizinische Universitatsklinik Graz
🇦🇹
Graz Steiermark, Austria
Hopital Bretonneau
🇫🇷
Tours Cedex, France
Azienda Ospedaliera Careggi
🇮🇹
Firenze (FI), Italy
Ospedale San Martino
🇮🇹
Genova, Italy
Nizhniy Novgorod City Oncology Center
🇷🇺
Nizhny Novgorod, Russian Federation
Clinica Especializada ISIS
🇦🇷
Santa Fe, Argentina
Cliniques Universitaires Saint-Luc
🇧🇪
Bruxelles, Belgium
UZ Gent
🇧🇪
Gent, Belgium
The Ottawa Hospital Regional Cancer Center
🇨🇦
Ottawa, Ontario, Canada
McGill University Health Centre, Department of Oncology, Gerald Bronfman Center
🇨🇦
Montreal, Quebec, Canada
Markusovszky Teaching Hospital, Dept. of Oncoradiology, Sec. Med. Oncology
🇭🇺
Szombathely, Hungary
UO di Oncologia
🇮🇹
Sora, Italy
Centrum Onkologii Instytut M. Sklodowskiej Curie w Warszawie Oddzial Gilwice
🇵🇱
Gilwice, Poland
Szpital Kiniczny Przemienienia Panskiego Uniwersyteu Medycznego im Karola Marcinkowskiego w Poznaniu
🇵🇱
Poznan, Poland
Institut Curie
🇫🇷
Paris, France
University Hospital Center Zagreb
🇭🇷
Zagreb, Croatia
CEPHO-Centro de Estudos e Pesquisa de Hematologia e oncologia
🇧🇷
Santo Andre, SP, Brazil
Clinical Hospital Osijek
🇭🇷
Osijek, Croatia
Debrecen Medical University, Department of Oncology
🇭🇺
Debrecen, Hungary
Ospedale "Vito Fazzi" - Lecce
🇮🇹
Lecce (LE), Italy
Instituto Nacional do Cancer-Unidade III (INCA III)
🇧🇷
Rio De Janiero, RJ, Brazil
University of Pecs
🇭🇺
Pecs, Hungary
Oncology Care Associates, P.L.L.C.
🇺🇸
Saint Joseph, Michigan, United States
Centro Regional Integrado de Oncologia-CRIO
🇧🇷
Fortaleza, CE, Brazil
Centrum Onkologii Instytut im M. Sklodowskiej Curie w Warszawie
🇵🇱
Warszawa, Poland
Krasnodar Territory Clinical Oncology Center
🇷🇺
Krasnodar, Russian Federation
City Clinical Hospital #1
🇷🇺
Novosibirisk, Russian Federation
Semmelweis Medical University, III. Dep. of Internal Med.
🇭🇺
Budapest, Hungary
Clinica de Oncologia Medica
🇧🇷
Sao Paulo, SP, Brazil
Szpital Morski im PCK w Gdyni Gdynskie Centrum Onkologii
🇵🇱
Gdynia, Poland
Centrum Onkologii Instytut M Sklodowskiej Curie, Oddzial w Krakowie
🇵🇱
Krakow, Poland
Burdenko Main Military Hospital
🇷🇺
Moscow, Russian Federation
Kazan State Medical University
🇷🇺
Kazan, Russian Federation
State Institution of Healthcare Stavropol Region clinical Oncology dispensary
🇷🇺
Pyatigorsk, Russian Federation
Kantonsspital Oncology Haematology
🇨🇭
St. Gallen, Switzerland
St. Vincent Medical Center
🇺🇸
Portland, Oregon, United States
US Oncology St. Vincent's Hospital - Bruno Cancer Center
🇺🇸
Birmingham, Alabama, United States
Research Center
🇺🇸
Gilroy, California, United States
Florida Cancer Research Institute
🇺🇸
Davie, Florida, United States
US Oncology
🇺🇸
Yakima, Washington, United States
University of Iowa Hospital and Clinic
🇺🇸
Iowa City, Iowa, United States
Peachtree Hematology/Oncology Consultants, PC
🇺🇸
Atlanta, Georgia, United States
Hematology Oncology Clinic
🇺🇸
Baton Rouge, Louisiana, United States
North Shore Hematology/Oncology Associates
🇺🇸
East Setauket, New York, United States
Carolina Hematology Oncology Associates
🇺🇸
Charlotte, North Carolina, United States
Instituto Oncologico "Las Heras"
🇦🇷
Bahia Blanca, Buenos Aires, Argentina
Breast Clinica de la Mama
🇦🇷
La Plata, Buenos Aires, Argentina
Northwest Medical Specialists
🇺🇸
Tacoma, Washington, United States
Instituto FIDES especialidades Medicas
🇦🇷
La Plata, Buenos Aires, Argentina
Hospital Britanico
🇦🇷
C.a.b.a, Buenos Aires, Argentina
CER Instituto Medico
🇦🇷
Quilmes Oeste, Buenos Aires, Argentina
CITEM
🇦🇷
Quilmes, Buenos Aires, Argentina
Centro Medico San Roque
🇦🇷
Tucuman, San Miguel De Tucuman, Argentina
Hosptial Interzonal General de Mar del Plata
🇦🇷
Buenos Aires, Argentina
Clinica Universitaria Privada Reina Fabiola
🇦🇷
Cordoba, Argentina
Instituto de Oncologia y Especialidades Medicas
🇦🇷
Rosario Santa Fe, Argentina
The Queen Elizabeth Hospital
🇦🇺
Southport, Queensland, Australia
Maroondah Breast Clinic
🇦🇺
Melbourne, Australia
Servicio De Oncologia
🇦🇺
Woodville South, South Australia, Australia
Mater Medical Centre
🇦🇺
North Sydney, Australia
Mount Hospital
🇦🇺
Perth, Australia
AZ Groeninge, Campus Maria's Voorzienigheid
🇧🇪
Kortrijk, Belgium
Centro de Pesquisas e Estudios do Centro Goiano
🇧🇷
Giana, GO, Brazil
Hospital Erasto Gaertner
🇧🇷
Curitiba, PA, Brazil
CPO-Centro de Pesquisas em Oncologia
🇧🇷
Porto Alegre, RS, Brazil
Santo Andre Diagnosticos e Tratamentos
🇧🇷
Santo Andre, SP, Brazil
Hospital Amaral Carvalho
🇧🇷
Vila Assis, SP, Brazil
Hospital Jihlava
🇨🇿
Jihlava, Czechia
Fakultni Thomayerova Nemocnice
🇨🇿
Prague, Czechia
General Faculty Hospital Prague
🇨🇿
Prague, Czechia
University Hospital for Tumors Zagreb
🇭🇷
Zagreb, Croatia
Clinic of Radiotherapy and Oncology
🇨🇿
Praha 10, Czechia
Hopital Jean Minjoz
🇫🇷
Besancon, France
Polyclinique Boredaux Nord Aquitaine
🇫🇷
Bordeaux, France
Centre Paul Papin
🇫🇷
Agners Cedex 01, France
Ustav radia ni onkologie 1. LF UK a FNB
🇨🇿
Praha, Czechia
Centre Francois Baclesse Caen
🇫🇷
Caen Cedex 05, France
Centre Jean Perrin - CRLC
🇫🇷
Clermont-Ferrand Cedex 01, France
Centre Georges-Francois Lecierc
🇫🇷
Dijon Cedex, France
Hopital Edourad Herriot
🇫🇷
Lyon, France
Clinique Armoricaine de Radiologie
🇫🇷
Saint Brieuc Cedex, France
Istituto Clinico Humanitas
🇮🇹
Rozzano, Italy
Istituto Scientifico San Raffaele
🇮🇹
Milano, Italy
Republic Clinical Oncology Dispensary
🇷🇺
Izhervsk Udmurtia, Russian Federation
Pavlov Medical University
🇷🇺
St. Petersburg, Russian Federation
Republican Oncology Center
🇷🇺
Petrozavodsk, Russian Federation
NN Petrov Research Institute of Oncology
🇷🇺
St. Petersburg, Russian Federation
Tomsk Regional Oncology Dispensary
🇷🇺
Tomsk, Russian Federation
Eastern Cape Oncology Centre, GVI, St Georges Hospital
🇿🇦
Port Elizabeth, Eastern Cape, South Africa
Panorama Medical Centre
🇿🇦
Panorama, Cape Town, South Africa
Sandton Oncology Centre
🇿🇦
Johannesburg, South Africa
GUZ YO Regional Clinical Oncology Hospital
🇷🇺
Yaroslavl, Russian Federation
Hospital Vall d Hebron
🇪🇸
Barcelona, Spain
Hospital Universitario de Girona Dr. Josep Trueta
🇪🇸
Gerona, Spain
Pretoria Academic Hospital
🇿🇦
Pretoria, South Africa
Complejo Hospitalario de Jaen
🇪🇸
Jaen, Spain
Hospital Universitario de Canarias
🇪🇸
Santa Cruz de Tenerife, Spain
Hospital Unversitatio de Salamanca
🇪🇸
Salamanca, Spain
Hospital Mutua de Terrassa
🇪🇸
Barcelona, Spain
Spital Thun-Simmental AG
🇨🇭
Thun, Switzerland
Inselspital Bern
🇨🇭
Bern Bern, Switzerland