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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01572727




Registration number
NCT01572727
Ethics application status
Date submitted
4/04/2012
Date registered
6/04/2012
Date last updated
9/03/2017

Titles & IDs
Public title
A Study of the Experimental Drug BKM120 With Paclitaxel in Patients With HER2 Negative, Locally Advanced or Metastatic Breast Cancer, With or Without PI3K Activation
Scientific title
A Randomized, Double-blind, Placebo Controlled, Phase II/III Study of BKM120 Plus Paclitaxel in Patients With HER2 Negative Inoperable Locally Advanced or Metastatic Breast Cancer, With or Without PI3K Pathway Activation.
Secondary ID [1] 0 0
2011-005932-24
Secondary ID [2] 0 0
CBKM120F2202
Universal Trial Number (UTN)
Trial acronym
BELLE-4
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 - Paclitaxel
Treatment: Drugs - BKM120 matching placebo
Treatment: Drugs - BKM120

Experimental: BKM120 and paclitaxel - Adult females with histologically confirmed, inoperable, locally advanced or metastatic HER2- BC who received study drug plus paclitaxel.

Active Comparator: Placebo and paclitaxel - Adult females with histologically confirmed, inoperable, locally advanced or metastatic HER2- BC who received placebo plus paclitaxel.


Treatment: Drugs: Paclitaxel
intravenous paclitaxel 80 mg/m2 per week given until progression

Treatment: Drugs: BKM120 matching placebo
Buparlisib maching plaxcebo were supplied as 100 mg and 50 mg hard gelatin capsules.
Buparlisib placebo was dosed on a flat scale of mg/day and was not adjusted to body weight or body surface area.

Treatment: Drugs: BKM120
Buparlisib (BKM120) were supplied as 100 mg and 50 mg hard gelatin capsules. Buparlisib was dosed on a flat scale of mg/day and was not adjusted to body weight or body surface area.

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

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS)Assessed by Local Investigator's Assessment (Phase ll) - PFS was defined as the time from the date of randomization to the date of the event, defined as the first radiologically documented disease progression or death due to any cause. Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Timepoint [1] 0 0
Every 8 weeks from randomization until disease progression up to 10 months after futility was analyzed
Secondary outcome [1] 0 0
Overall Survival by Kaplan-Meier Estimate (Phase ll) - Overall survival (OS) was defined as the time from date of randomization to date of death due to any cause. If a patient was not known to have died by the date of analysis cut-off, OS was censored at the date of last contact.
Timepoint [1] 0 0
every 3 months until death, lost to follow-up, or withdrawal of consent to survival follow-up, up to 10 months after futility was analyzed
Secondary outcome [2] 0 0
Overall Response Rate (Phase ll) - Percentage of patients with best overall response of complete response (CR) or partial response (PR) based on local investigator's assessment according to RECIST v1.1. According to this criteria, CR = at least two determinations of CR at least 4 weeks apart before progression; PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Timepoint [2] 0 0
every 8 weeks after randomization Up to 3 months after end of Treatment
Secondary outcome [3] 0 0
Duration of Response (Phase Lll) - time from the date of the first documented response (CR or PR, which had to be confirmed subsequently) to the date of the first radiologically documented disease progression or death due to disease
Timepoint [3] 0 0
every 8 weeks after randomization Up to 3 months after end of Treatment
Secondary outcome [4] 0 0
Time to Response (Phase Lll) - time from date of randomization until first documented response (CR or PR, which has to be confirmed subsequently).
Timepoint [4] 0 0
every 8 weeks after randomization Up to 3 months after end of Treatment
Secondary outcome [5] 0 0
Clinical Benefit Rate (CBR) (Phase ll) - CBR was defined as the percentage of patients with an overall response of CR or PR or SD or non-CR/non-PD lasting more than 24 weeks based on local Investigator's assessment according to RECIST v1.1.
Timepoint [5] 0 0
every 8 weeks after randomization Up to 3 months after end of Treatment
Secondary outcome [6] 0 0
Plasma Concentration-time Profiles of BKM120 - Pharmacokinetics (PK) (Phase Lll) - Summary statistics for PK: plasma concentration-time profiles of BKM120 and appropriate individual PK parameters based on population PK model , if deemed appropriate; each cycle = 28 days
Timepoint [6] 0 0
Cycle 1 day 1, 15, 16, 22 and Cycle 2 day 1.
Secondary outcome [7] 0 0
Time to Definitive Deterioration of ECOG Performance Status (Phase Lll) - Time to definitive deterioration of the ECOG performance status from baseline
Timepoint [7] 0 0
every 4 weeks

Eligibility
Key inclusion criteria
- Breast cancer that is locally advanced or metastatic

- HER2 negative disease, and a known hormone receptor status - ER/PgR (common breast
cancer classification tests)

- A tumor sample must be shipped to a central lab for identification of biomarkers (PI3K
activation status) before randomization

- Adequate bone marrow and organ function

- Measurable or non-measurable disease
Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
- Prior chemotherapy for locally advanced or metastatic disease

- Previous treatment with PI3K or AKT inhibitors

- Patient has symptomatic CNS metastases

- Concurrent malignancy or malignancy within 3 years of study enrollment

- Hematopoietic colony-stimulating growth factors or radiation within 2-4 weeks prior to
starting study drug

- Increasing or chronic treatment (> 5 days) with corticosteroids or another
immunosuppressive agent

- Active heart (cardiac) disease as defined in the protocol

- Known hypersensitivity or contraindications to use paclitaxel

- Pregnant or nursing (lactating) woman

- Certain scores on an anxiety and depression mood questionaire given at screening

- Other protocol defined criteria may apply

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 2/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)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Novartis Investigative Site - Sydney
Recruitment hospital [2] 0 0
Novartis Investigative Site - Geelong
Recruitment hospital [3] 0 0
Novartis Investigative Site - Parkville
Recruitment hospital [4] 0 0
Novartis Investigative Site - Nedlands
Recruitment postcode(s) [1] 0 0
2060 - Sydney
Recruitment postcode(s) [2] 0 0
3220 - Geelong
Recruitment postcode(s) [3] 0 0
3050 - Parkville
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
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Arizona
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Arkansas
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California
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Colorado
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Florida
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Georgia
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Kansas
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Kentucky
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Missouri
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Nebraska
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New Mexico
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New York
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Ohio
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Oklahoma
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Oregon
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Texas
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United States of America
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Virginia
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Austria
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Salzburg
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Austria
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Vienna
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Belgium
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Charleroi
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Belgium
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Liege
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Belgium
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Liège
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Belgium
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Ottignies
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Belgium
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Sint-Niklaas
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Belgium
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Wilrijk
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Brazil
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CE
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Brazil
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SP
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Canada
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Quebec
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Czech Republic
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Brno
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Czech Republic
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Olomouc
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Czech Republic
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Praha 2
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France
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Angers Cedex 02
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France
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Bordeaux
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France
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Creteil
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France
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La Roche sur Yon cedex 9
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France
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Le Mans Cedex
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France
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Marseille
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France
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Nice Cedex 2
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France
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Saint Herblain cedex
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France
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Toulouse Cedex 9
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France
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Villejuif Cedex
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Germany
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Bonn
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Germany
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Dresden
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Germany
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Erlangen
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Germany
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Frankfurt
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Germany
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Fulda
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Germany
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Mainz
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Germany
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Muenchen
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Germany
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Ravensburg
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Germany
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Ulm
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Hong Kong
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Hong Kong SAR
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Hungary
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Budapest
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Hungary
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Debrecen
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Hungary
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Szolnok
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Israel
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Ramat Gan
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Israel
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Tel Aviv
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Italy
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FE
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Italy
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GE
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Italy
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MB
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Italy
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ME
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Italy
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MI
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Japan
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Aichi
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Japan
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Hokkaido
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Japan
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Kanagawa
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Kumamoto
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Osaka
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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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Netherlands
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Breda
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Netherlands
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Rotterdam
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Russian Federation
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Russia
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Russian Federation
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St. Petersburg
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Singapore
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Singapore
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South Africa
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Johannesburg
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Spain
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Andalucia
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Spain
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Catalunya
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Spain
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Comunidad Valenciana
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Galicia
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Santa Cruz de Tenerife
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Madrid
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Zaragoza
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Taoyuan/ Taiwan ROC
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New Taipei City
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Taiwan
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Taipei
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United Kingdom
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Kent
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United Kingdom
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Glasgow - Scotland
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United Kingdom
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London
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United Kingdom
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Wirral

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

Ethics approval
Ethics application status

Summary
Brief summary
This study evaluated whether the addition of daily BKM120 to weekly paclitaxel was effective
and safe in treating patients with HER2- locally advanced or metastatic breast cancer.
Trial website
https://clinicaltrials.gov/show/NCT01572727
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

Summary results
Other publications