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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00388726




Trial ID
NCT00388726
Ethics application status
Date submitted
13/10/2006
Date registered
16/10/2006
Date last updated
25/07/2014

Titles & IDs
Public title
E7389 Versus Treatment of Physician's Choice in Patients With Locally Recurrent or Metastatic Breast Cancer
Scientific 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
Secondary ID [1] 0 0
2006-001949-34
Secondary ID [2] 0 0
E7389-G000-305
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - E7389
Treatment: Drugs - Physician's Choice

Experimental: 1 -

Active Comparator: 2 -


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

Treatment: Drugs: 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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival - Defined as the time from the date of randomization until the date of death from any cause.
Timepoint [1] 0 0
From date of randomization until death from any cause
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Until disease progression or death.
Secondary outcome [2] 0 0
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).
Timepoint [2] 0 0
Until Day 30 or every 3 months during Follow-up period for patients who complete study without PD.
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
From first documented CR or PR until disease progression or death.
Secondary outcome [4] 0 0
Safety Parameters: Adverse Events (AEs), Laboratory Parameters, Concomitant Medication, Electrocardiograms (ECGs), and Study Drug Exposure.
Timepoint [4] 0 0
AEs and conmeds - until study termination; lab tests - Day 1 and weekly until study termination; ECGs - Day 1 and at study termination.

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,SA
Recruitment hospital [1] 0 0
The Queen Elizabeth Hospital - Southport
Recruitment hospital [2] 0 0
Servicio De Oncologia - Woodville South
Recruitment hospital [3] 0 0
Maroondah Breast Clinic - Melbourne
Recruitment hospital [4] 0 0
Mater Medical Centre - North Sydney
Recruitment hospital [5] 0 0
Mount Hospital - Perth
Recruitment hospital [6] 0 0
Royal Perth Hospital, Department of Medical Oncology - Perth
Recruitment postcode(s) [1] 0 0
4215 - Southport
Recruitment postcode(s) [2] 0 0
5011 - Woodville South
Recruitment postcode(s) [3] 0 0
3135 - Melbourne
Recruitment postcode(s) [4] 0 0
2060 - North Sydney
Recruitment postcode(s) [5] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Indiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Iowa
Country [9] 0 0
United States of America
State/province [9] 0 0
Louisiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Michigan
Country [11] 0 0
United States of America
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Missouri
Country [12] 0 0
United States of America
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Montana
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United States of America
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Nevada
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United States of America
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New York
Country [15] 0 0
United States of America
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North Carolina
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United States of America
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Oregon
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United States of America
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Texas
Country [18] 0 0
United States of America
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Washington
Country [19] 0 0
Argentina
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Buenos Aires
Country [20] 0 0
Argentina
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Pcia. Santa Fe
Country [21] 0 0
Argentina
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San Miguel de Tucuman
Country [22] 0 0
Argentina
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Cordoba
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Argentina
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Rosario Santa Fe
Country [24] 0 0
Argentina
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Santa Fe
Country [25] 0 0
Austria
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Graz Steiermark
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Austria
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Salzburg
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Belgium
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Brussels
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Belgium
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Bruxelles
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Belgium
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Charleroi
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Belgium
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Gent
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Belgium
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Kortrijk
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Brazil
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CE
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Brazil
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GO
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Brazil
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PA
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RJ
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RS
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SP
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Canada
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Ontario
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Quebec
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Croatia
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Osijek
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Zagreb
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Brno
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Jihlava
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Prague
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Czech Republic
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Praha 10
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Czech Republic
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Praha
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France
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Agners Cedex 01
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Besancon
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Bordeaux
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France
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Caen Cedex 05
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France
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Clermont-Ferrand Cedex 01
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France
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Dijon Cedex
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France
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Lyon
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France
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Paris
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France
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Saint Brieuc Cedex
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France
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Tours Cedex
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Hungary
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Budapest
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Debrecen
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Pecs
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Szombathely
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Firenze (FI)
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Genova
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Lecce (LE)
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Italy
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Milano
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Italy
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Roma
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Italy
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Rozzano
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Italy
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Sora
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Poland
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Gdansk
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Gdynia
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Gilwice
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Krakow
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Poznan
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Poland
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Szczecin
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Poland
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Warszawa
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Russian Federation
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Izhervsk Udmurtia
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Russian Federation
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Kazan
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Russian Federation
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Krasnodar
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Russian Federation
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Moscow
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Russian Federation
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Nizhny Novgorod
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Russian Federation
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Novosibirisk
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Russian Federation
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Petrozavodsk
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Russian Federation
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Pyatigorsk
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Russian Federation
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St Petersburg
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Russian Federation
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St. Petersburg
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Russian Federation
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Tomsk
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Russian Federation
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Yaroslavl
Country [87] 0 0
South Africa
State/province [87] 0 0
Cape Town
Country [88] 0 0
South Africa
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Eastern Cape
Country [89] 0 0
South Africa
State/province [89] 0 0
Johannesburg
Country [90] 0 0
South Africa
State/province [90] 0 0
Pretoria
Country [91] 0 0
Spain
State/province [91] 0 0
Barcelona
Country [92] 0 0
Spain
State/province [92] 0 0
Gerona
Country [93] 0 0
Spain
State/province [93] 0 0
Jaen
Country [94] 0 0
Spain
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Salamanca
Country [95] 0 0
Spain
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Santa Cruz de Tenerife
Country [96] 0 0
Spain
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Sevilla
Country [97] 0 0
Spain
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Zanagoza
Country [98] 0 0
Switzerland
State/province [98] 0 0
Aarau
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Switzerland
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Bern Bern
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Switzerland
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St. Gallen
Country [101] 0 0
Switzerland
State/province [101] 0 0
Thun
Country [102] 0 0
Switzerland
State/province [102] 0 0
Winterhur

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Eisai Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Eisai Limited
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00388726
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jantien Wanders, M.D.
Address 0 0
Eisai Limited
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries