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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00388726
• Other study ID #: E7389-G000-305
• Secondary ID: 2006-001949-34
• Status: Completed
• Phase: Phase 3
• Start date: November 2006
• Est. completion date: June 2013

Study information

• Verified date: July 2014
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 762
• Est. completion date: June 2013
• Est. primary completion date: May 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• E7389
1.4 mg/m^2 intravenous (IV) infusion given over 2-5 minutes on Days 1 and 8 every 21 days.
• 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.

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Eisai Inc.	Eisai Limited

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Croatia,  Czechia,  France,  Hungary,  Italy,  Poland,  Russian Federation,  South Africa,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	Defined as the time from the date of randomization until the date of death from any cause.	From date of randomization until death from any cause
Secondary	Progression-Free Survival.	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.	Until disease progression or death.
Secondary	Best Overall Response	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).	Until Day 30 or every 3 months during Follow-up period for patients who complete study without PD.
Secondary	Duration of Response.	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.	From first documented CR or PR until disease progression or death.
Secondary	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)