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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00876395




Registration number
NCT00876395
Ethics application status
Date submitted
2/04/2009
Date registered
6/04/2009

Titles & IDs
Public title
Everolimus in Combination With Trastuzumab and Paclitaxel in the Treatment of HER2 Positive Locally Advanced or Metastatic Breast Cancer
Scientific title
A Randomized Phase III, Double-Blind, Placebo-Controlled Multicenter Trial of Everolimus in Combination With Trastuzumab and Paclitaxel, as First Line Therapy in Women With HER2 Positive Locally Advanced or Metastatic Breast Cancer
Secondary ID [1] 0 0
2008-006556-21
Secondary ID [2] 0 0
CRAD001J2301
Universal Trial Number (UTN)
Trial acronym
BOLERO-1
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 - Everolimus
Treatment: Drugs - Placebo
Treatment: Drugs - Trastuzumab
Treatment: Drugs - Paclitaxel

Experimental: Everolimus + Paclitaxel + Trastuzumab - Everolimus 10 mg daily in combination with paclitaxel 80mg/m2 weekly on days 1, 8, 15 and trastuzumab 2mg/kg weekly on days 1, 8, 15, 22

Placebo comparator: Placebo + Paclitaxel + Trastuzumab - Placebo of everolimus 10 mg daily in combination with paclitaxel 80mg/m2 weekly on days 1, 8, 15 and trastuzumab 2mg/kg weekly on days 1, 8, 15, 22


Treatment: Drugs: Everolimus
Everolimus was administered in a continuous oral daily dosing of 10 mg (two 5-mg tablets).

Treatment: Drugs: Placebo
Everolimus placebo was administered in a continuous oral daily dosing of 10 mg (two 5-mg tablets).

Treatment: Drugs: Trastuzumab
Trastuzumab, 2 mg/kg weekly was used intravenously.

Treatment: Drugs: Paclitaxel
Paclitaxel, 80 mg/m2 weekly was used intravenously.

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

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS) Per Investigators' Assessment Based on Local Radiology Review - Full Population
Timepoint [1] 0 0
date of randomization to the date of first documented tumor progression or death from any cause, whichever occurs first, reported between day of first patient randomized up to about 56 months
Primary outcome [2] 0 0
Progression-free Survival (PFS) Per Investigators' Assessment Based on Local Radiology Review - (Hormone Receptor (HR)-Negative Population
Timepoint [2] 0 0
date of randomization to the date of first documented tumor progression or death from any cause, whichever occurs first, reported between day of first patient randomized up to about 56 months
Secondary outcome [1] 0 0
Overall Survival (OS) - Full Population
Timepoint [1] 0 0
up to about 76 months
Secondary outcome [2] 0 0
Overall Survival (OS) - HR-negative Population
Timepoint [2] 0 0
up to about 76 months
Secondary outcome [3] 0 0
Overall Response Rate (ORR) - Full Population
Timepoint [3] 0 0
up to about 23 months
Secondary outcome [4] 0 0
Overall Response Rate (ORR) - HR-negative Population
Timepoint [4] 0 0
up to about 23 months
Secondary outcome [5] 0 0
Clinical Benefit Rate (CBR) Equal to or Greater Than 24 Weeks - Full Population
Timepoint [5] 0 0
up to about 23 months
Secondary outcome [6] 0 0
Clinical Benefit Rate (CBR) Equal to or Greater Than 24 Weeks - HR-negative Population
Timepoint [6] 0 0
up to about 23 months
Secondary outcome [7] 0 0
Time to Overall Response Based on Investigator - Full Population
Timepoint [7] 0 0
up to about 23 months
Secondary outcome [8] 0 0
Time to Overall Response Based on Investigator - HR-negative Population
Timepoint [8] 0 0
up to about 23 months
Secondary outcome [9] 0 0
Overall Response (OR) - Full Population
Timepoint [9] 0 0
up to about 23 months
Secondary outcome [10] 0 0
Overall Response (OR) - HR-negative Population
Timepoint [10] 0 0
up to about 23 months
Secondary outcome [11] 0 0
Everolimus Blood Level Concentrations at Steady States for Everolimus
Timepoint [11] 0 0
predose, 2 hours post-dose at Cycle 2/Day 1, Cycle 2/Day 15, Cycle 2/ Day 22
Secondary outcome [12] 0 0
Paclitaxel Plasma Concentrations
Timepoint [12] 0 0
Cycle 2/Day 15 (Pre-infusion and end of infusion)
Secondary outcome [13] 0 0
Trastuzumab Serum Concentrations
Timepoint [13] 0 0
Cycle 4/Day 1 (Pre-infusion and end of infusion)
Secondary outcome [14] 0 0
Time to Deterioration of Eastern Cooperative Oncology Group Performance Status (ECOG-PS) Score - Full Population
Timepoint [14] 0 0
up to about 56 months
Secondary outcome [15] 0 0
Time to Deterioration of Eastern Cooperative Oncology Group Performance Status (ECOG-PS) Score - HR-negative Population
Timepoint [15] 0 0
up to about 56 months

Eligibility
Key inclusion criteria
* Adult Women (= 18 years old).
* Histologically or cytologically confirmed invasive breast carcinoma with local recurrence or radiological evidence of metastatic disease.
* Must have at least one lesion that can be accurately measured or bone lesions in the absence of measurable disease.
* HER2+ patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive).
* Prior trastuzumab and/or chemotherapy (taxanes included) as neo-adjuvant or adjuvant treatment is allowed but should be discontinued > 12 months prior to randomization.
* Prior treatment for breast cancer with endocrine therapy (adjuvant or metastatic settings) is allowed but should be discontinued at randomization. Patients treated with bisphosphonates at entry or who start bisphosphonates during study may continue this therapy during protocol treatment.
* Documentation of negative pregnancy test.
* Organ functions at time of inclusion.
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
* Prior mTOR inhibitors for the treatment of cancer.
* Other anticancer therapy for locally advanced or metastatic breast cancer except for prior hormonal therapy.
* Patients with only non-measurable lesions other than bone metastasis (e.g. pleural effusion, ascites, etc).
* Radiotherapy to = 25% of the bone marrow within 4 weeks prior to randomization
* History of central nervous system metastasis.
* Impairment of gastrointestinal (GI) function or GI disease or active ulceration of the upper gastrointestinal tract.
* Serious peripheral neuropathy.
* Cardiac disease or dysfunction.
* Uncontrolled hypertension.
* HIV.
* Pregnant,

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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
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,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Southport
Recruitment hospital [2] 0 0
Novartis Investigative Site - East Bentleigh
Recruitment postcode(s) [1] 0 0
4215 - Southport
Recruitment postcode(s) [2] 0 0
3165 - East Bentleigh
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
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
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United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
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United States of America
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Indiana
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United States of America
State/province [8] 0 0
Kansas
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United States of America
State/province [9] 0 0
Nebraska
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
Oregon
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United States of America
State/province [12] 0 0
Tennessee
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
United States of America
State/province [14] 0 0
Virginia
Country [15] 0 0
Argentina
State/province [15] 0 0
Buenos Aires
Country [16] 0 0
Argentina
State/province [16] 0 0
Misiones
Country [17] 0 0
Argentina
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Sante Fe
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Argentina
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Viedma
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Argentina
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Capital Federal
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Argentina
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Cordoba
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Belgium
State/province [21] 0 0
Charleroi
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Belgium
State/province [22] 0 0
Hasselt
Country [23] 0 0
Belgium
State/province [23] 0 0
Verviers
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Belgium
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Wilrijk
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Belgium
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Yvoir
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Brazil
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MG
Country [27] 0 0
Brazil
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RJ
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Brazil
State/province [28] 0 0
SP
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Canada
State/province [29] 0 0
Quebec
Country [30] 0 0
China
State/province [30] 0 0
Guangdong
Country [31] 0 0
China
State/province [31] 0 0
Heilongjiang
Country [32] 0 0
China
State/province [32] 0 0
Jiangsu
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China
State/province [33] 0 0
Shanghai
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China
State/province [34] 0 0
Zhejiang
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China
State/province [35] 0 0
Beijing
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China
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Guangzhou
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Colombia
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Cundinamarca
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Colombia
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Bogota
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Colombia
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Florida Blanca
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Colombia
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Monteria
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Egypt
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Alexandria
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Egypt
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Cairo
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France
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Limoges
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France
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Rouen
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France
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Saint-Herblain Cédex
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France
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Strasbourg Cedex
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France
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Thonon-les-Bains Cedex
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France
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Toulouse Cedex 9
Country [49] 0 0
France
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Villejuif Cedex
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Germany
State/province [50] 0 0
Berlin
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Germany
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Chemnitz
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Germany
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Esslingen
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Germany
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Kiel
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Germany
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Muenster
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Greece
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GR
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Greece
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Athens
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Greece
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Heraklion Crete
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Hong Kong
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Hong Kong SAR
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Hong Kong
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Shatin, New Territories
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Hong Kong
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Tuen Mun
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Ireland
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Cork
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Ireland
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Dublin 4
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Ireland
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Dublin 8
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Ireland
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Dublin 9
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Italy
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MB
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Italy
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MO
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Italy
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PD
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Italy
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RM
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Italy
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Napoli
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Japan
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Aichi
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Japan
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Chiba
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Japan
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Fukuoka
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Japan
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Gunma
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Japan
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Hokkaido
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Japan
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Kanagawa
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Japan
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Kumamoto
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Japan
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Kyoto
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Japan
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Osaka
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Japan
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Saitama
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Japan
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Tokyo
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Korea, Republic of
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Korea
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Korea, Republic of
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Seoul
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Lebanon
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Ashrafieh
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Lebanon
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Beirut
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Mexico
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Distrito Federal
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Mexico
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Veracruz
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Peru
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Lima
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Puerto Rico
State/province [88] 0 0
San Juan
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Russian Federation
State/province [89] 0 0
Tatarstan Republic
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Russian Federation
State/province [90] 0 0
Moscow
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Russian Federation
State/province [91] 0 0
St Petersburg
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Russian Federation
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St. Petersburg
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South Africa
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Bloemfontein
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South Africa
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Durban
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South Africa
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Pretoria
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Switzerland
State/province [96] 0 0
Genève
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Switzerland
State/province [97] 0 0
Zuerich
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Taiwan
State/province [98] 0 0
Taiwan, ROC
Country [99] 0 0
Taiwan
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Kaohsiung
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Taiwan
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Taichung
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Taiwan
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Taipei
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Taiwan
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Taoyuan
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Turkey
State/province [103] 0 0
Altunizade
Country [104] 0 0
Turkey
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Ankara
Country [105] 0 0
Turkey
State/province [105] 0 0
Izmir
Country [106] 0 0
United Kingdom
State/province [106] 0 0
Cornwall
Country [107] 0 0
United Kingdom
State/province [107] 0 0
London
Country [108] 0 0
United Kingdom
State/province [108] 0 0
Sutton
Country [109] 0 0
Venezuela
State/province [109] 0 0
Estado Carabobo

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.