Breast CancerPhase 3BELLE-2NCT01610284
Phase III Study of BKM120/Placebo With Fulvestrant in Postmenopausal Patients With Hormone Receptor Positive HER2-negative Locally Advanced or Metastatic Breast Cancer Refractory to Aromatase Inhibitor
A Phase 3 study testing Fulvestrant and BKM120 in people with Breast Cancer, run by Novartis Pharmaceuticals at 268 sites in 29 countries.
Trial summary
This study was a multi-center, randomized, double-blind, placebo controlled Phase III study to determine the efficacy and safety of treatment with buparlisib plus fulvestrant versus fulvestrant plus placebo in postmenopausal women with hormone Receptor-positive (HR-positive), human epidermal growth factor receptor… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Fulvestrant and BKM120
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,147 participants
- Where
- 268 sitesin 29 countries
- Study dates
- 7 Aug 2012to 19 Apr 2019
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Locally advanced or metastatic breast cancer
- HER2-negative and hormone receptor-positive status (common breast cancer classification tests)
- Postmenopausal woman
- A tumor sample must be shipped to a Novartis designated laboratory for identification of biomarkers (PI3K activation status)
- Progression or recurrence of breast cancer while on or after aromatase inhibitor treatment
- Measurable disease or non measurable disease bone lesions in the absence of measurable disease as per RECIST 1.1
- Adequate bone marrow and organ function defined by laboratory values
Who cannot join
- Previous treatment with PI3K inhibitors, AKT inhibitors, mTOR inhibitor or fulvestrant
- More than one prior chemotherapy line for metastatic disease
- Symptomatic brain metastases
- Increasing or chronic treatment (> 5 days) with corticosteroids or another immunosuppressive agent
- Active heart (cardiac) disease as defined in the protocol
- Certain scores on an anxiety and depression mood questionnaires
Trial locations and contacts
268 sites in 29 countries.
268 sites in 29 countries
United States61 sites
Shapiro and Stafford and Yee and Polanski Study Coordinator
Arcadia, California, 91007
Mercy Medical Center Mercy Medical SC
Baltimore, Maryland, 21202
Sidney Kimmel Comprehensive Cancer Center Johns Hopkins Med Sidney/John Hopkins
Baltimore, Maryland, 21231
St. Luke's Hospital and Health Network St Luke's (2)
Bethlehem, Pennsylvania, 18015
Massachusetts General Hospital SC
Boston, Massachusetts, 02114
Hackensack Meridian Health
Brick, New Jersey, 08724
Charleston Hematology Oncology Association PA
Charleston, South Carolina, 29414
Levine Cancer Institute Levine Cancer Institute
Charlotte, North Carolina, 28203
Case Western Reserve SC
Cleveland, Ohio, 44106-5000
Texas Oncology P A Midtown
Dallas, Texas, 75251
Texas Oncology P A TX Onc - Bedford
Dallas, Texas, 75251
Texas Oncology P A TX Onc - Med City Dallas
Dallas, Texas, 75251
Texas Oncology P A TX Onc - Southwest
Dallas, Texas, 75251
Georgia Cancer Specialists SC
Decatur, Georgia, 30033
Kaiser Permanente Northwest Kaiser
Denver, Colorado
North Shore University Health System
Evanston, Illinois, 60201
Highlands Oncology Group
Fayetteville, Arkansas, 72703
Frederick Memorial Hospital Fred. Mem. Hosp.
Frederick, Maryland, 21701
Cancer Care Associates Dept.ofCancerCareAssoc.
Fresno, California, 93720
St. Jude Heritage Medical Group Virginia Crosson Cancer Center
Fullerton, California, 92835
Cadence Health
Geneva, Illinois, 60134
Cancer TEAM Bellin Health Belin Health
Green Bay, Wisconsin, 54313
Rocky Mountain Cancer Centers RMCC
Greenwood Village, Colorado
Memorial Regional Cancer Center MRCC
Hollywood, Florida, 33021
Oncology Consultants Oncology Consultants, P.A.
Houston, Texas, 77024
Cancer Specialists of North Florida SC - F2302
Jacksonville, Florida, 32258
West Michigan Cancer Center Dept of Oncology
Kalamazoo, Michigan, 49007
Kadlec Clinic Hematology and Oncology Kadlec Clinic Hematology & Onc
Kennewick, Washington, 99336
Tennessee Cancer Specialists
Knoxville, Tennessee, 37909
University of California San Diego - Moores Cancer Center UCSD 3
La Jolla, California, 92093-0658
Clinical Research Alliance SC-2
Lake Success, New York, 11042
Los Angeles Hematology/Oncology Medical Group LA Cancer Network
Los Angeles, California, 90017
USC Kenneth Norris Comprehensive Cancer Center Dept.ofNorrisCompCancerCtr (3)
Los Angeles, California, 90053
University of California at Los Angeles Dept. of UCLA
Los Angeles, California, 90095
Dean Health System Dean Hematology Oncology
Madison, Wisconsin, 53717
University of Wisconsin / Paul P. Carbone Comp Cancer Center Univ Wisc 3
Madison, Wisconsin, 53792-6164
University of Miami Univ Miami 2
Miami, Florida, 33136
University of South Alabama / Mitchell Cancer Institute Deptof Mitchell Cancer Inst(2)
Mobile, Alabama, 36688
West Virginia University/ Mary Babb Randolph Cancer Center Dept of Oncology
Morgantown, West Virginia, 26506
Cancer Care and Hematology Specialists of Chicagoland Niles
Multiple Locations, Illinois
Vanderbilt University Medical Center Vanderbilt - Thompson Ln
Nashville, Tennessee, 37232
Memorial Sloan Kettering Dept Onc
New York, New York, 10017
MD Anderson Cancer Center - Orlando MD Orlando
Orlando, Florida, 32806
Ventura County Hematology and Oncology PMK Medical Group
Oxnard, California, 93030
The Valley Hospital / Luckow Pavillion
Paramus, New Jersey, 07652
Arizona Oncology Associates Dept of Oncology
Phoenix, Arizona
Northwest Cancer Specialists Portland Loc
Portland, Oregon, 97210
Oncology Hematology Associates of Southeast Virginia Salem VA Branch
Roanoke, Virginia, 24014
University of Rochester Medical Center Univ Rochester
Rochester, New York, 14642
Maryland Oncology Hematology, P.A. SC
Rockville, Maryland, 20850
Utah Cancer Specialists Dept.of Utah Cancer Spec. (3)
Salt Lake City, Utah, 84106
Cancer Therapy and Research Center UT Health Science Center Institute for Drug Development
San Antonio, Texas, 78229
Coastal Integrative Cancer Care
San Luis Obispo, California, 93401
Santa Barbara Hematolgy Oncology Medical Group
Santa Barbara, California, 93105
Central Coast Medical Oncology Corporation
Santa Maria, California, 93454
St Joseph Heritage Healthcare Dept. of RRMG (4)
Santa Rosa, California, 94503
Washington University School of Medicine Regulatory
St Louis, Missouri, 63110
Hematology and Oncology Association at Bridgepoint Hem Onc Bridgepoint
Tupelo, Mississippi, 38801
Granada Hills Cancer Center
Valencia, California, 91355
Cancer Center of Kansas CCK
Wichita, Kansas, 67214-3728
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
Spain28 sites
Novartis Investigative Site
Barcelona, Catalonia, 08003
Novartis Investigative Site
Barcelona, Catalonia, 08024
Novartis Investigative Site
Barcelona, Catalonia, 08035
Novartis Investigative Site
Barcelona, Catalonia, 08036
Novartis Investigative Site
Barcelona, 08041
Novartis Investigative Site
Córdoba, Andalusia, 14004
Novartis Investigative Site
El Palmar, Murcia, 30120
Novartis Investigative Site
Elche, Alicante, 03203
Novartis Investigative Site
Jaén, Andalusia, 23007
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Las Palmas de Gran Canarias, Las Palmas de Gran Canaria, 35016
Novartis Investigative Site
Madrid, 28009
Novartis Investigative Site
Madrid, 28033
Novartis Investigative Site
Madrid, 28040
Novartis Investigative Site
Madrid, 28046
Novartis Investigative Site
Madrid, 28050
Novartis Investigative Site
Madrid, 28222
Novartis Investigative Site
Málaga, Andalusia, 29010
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Oviedo, Principality of Asturias, 33006
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San Sebastián de los Reyes, Madrid, 28702
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Seville, Andalusia, 41009
Novartis Investigative Site
Seville, Andalusia, 41013
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Seville, Andalusia, 41014
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Tarragona, Catalonia, 43007
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Toledo, Castille-La Mancha, 45071
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Valencia, Valencia, 46009
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Valencia, Valencia, 46010
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Valencia, Valencia, 46026
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Zaragoza, 50009
Italy22 sites
Novartis Investigative Site
Aviano, PN, 33081
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Bologna, 40138
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Catanzaro, CZ, 88100
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Cremona, CR, 26100
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Cuneo, CN, 12100
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Florence, FI, 50134
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Lido di Camaiore, LU, 55041
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Meldola, FC, 47014
Novartis Investigative Site
Milan, MI, 20122
Novartis Investigative Site
Milan, MI, 20133
Novartis Investigative Site
Milan, MI, 20141
Novartis Investigative Site
Milan, MI, 20162
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Mirano, VE, 30035
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Naples, 80131
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Pisa, PI, 56126
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Province of Macerata, MC, 62100
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Rimini, RN, 47900
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Roma, RM, 00128
Novartis Investigative Site
Roma, RM, 00161
Novartis Investigative Site
Roma, RM, 00189
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Rozzano, MI, 20089
Novartis Investigative Site
Torino, TO, 10126
France19 sites
Novartis Investigative Site
Angers, 49055
Novartis Investigative Site
Avignon, 84082
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Besançon, 25030
Novartis Investigative Site
Bordeaux, 33076
Novartis Investigative Site
Caen, 14021
Novartis Investigative Site
Clermont-Ferrand, 63011
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Dijon, Cote D Or, 21034
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Le Mans, 72015
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Lille, 59020
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Montpellier, 34298
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Nice, Alpes Maritimes, 06189
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Paris, 75010
Novartis Investigative Site
Paris, 75231
Novartis Investigative Site
Rouen, 76038
Novartis Investigative Site
Saint Priest En Jarez, Pays de la Loire Region, 42270
Novartis Investigative Site
Saint-Herblain Cédex, 44805
Novartis Investigative Site
Strasbourg, 67085
Novartis Investigative Site
Toulouse, 31059
Novartis Investigative Site
Villejuif, 94800
Germany16 sites
Novartis Investigative Site
Essen, 45147
Novartis Investigative Site
Hamburg, 20249
Novartis Investigative Site
Hanover, 30177
Novartis Investigative Site
Heidelberg, 69120
Novartis Investigative Site
Kiel, 24105
Novartis Investigative Site
Langen, Hesse, 63225
Novartis Investigative Site
Lübeck, Schleswig-Holstein, 23563
Novartis Investigative Site
Magdeburg, 39108
Novartis Investigative Site
Mainz, 55131
Novartis Investigative Site
Mannheim, 68165
Novartis Investigative Site
Mühlhausen, 99974
Novartis Investigative Site
München, 80638
Novartis Investigative Site
Recklinghausen, North Rhine-Westphalia, 45657
Novartis Investigative Site
Saarbrücken, 66113
Novartis Investigative Site
Velbert, 42551
Novartis Investigative Site
Würzburg, 97080
Canada15 sites
Novartis Investigative Site
Calgary, Alberta, T2N 4N2
Novartis Investigative Site
Cambridge, Ontario, N1R 3G2
Novartis Investigative Site
Edmonton, Alberta, T6G 1Z2
Novartis Investigative Site
Halifax, Nova Scotia, B3H 1V7
Novartis Investigative Site
Kelowna, British Columbia, V1Y 5L3
Novartis Investigative Site
Laval, Quebec, H7M 3L9
Novartis Investigative Site
London, Ontario, N6A 4L6
Novartis Investigative Site
Montreal, Quebec, H2L 4M1
Novartis Investigative Site
Newmarket, Ontario, J7Y 2P9
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Ottawa, Ontario, K1H 8L6
Novartis Investigative Site
Québec, Quebec, G1S 4L8
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Regina, Saskatchewan, S4T 7T1
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Toronto, Ontario, M4N 3M5
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Toronto, Ontario, M5G 2M9
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Vancouver, British Columbia, V5Z 4E6
Japan13 sites
Novartis Investigative Site
Fukuoka, Fukuoka, 811-1395
Novartis Investigative Site
Isehara, Kanagawa, 259-1193
Novartis Investigative Site
Kashiwa, Chiba, 277 8577
Novartis Investigative Site
Koto Ku, Tokyo, 135 8550
Novartis Investigative Site
Kumamoto, Kumamoto, 860-8556
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Maebashi, Gunma, 371 8511
Novartis Investigative Site
Nagoya, Aichi-ken, 464 8681
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Osaka, Osaka, 540-0006
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Osaka, Osaka, 541-8567
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Sakyo Ku, Kyoto, 606 8507
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Sapporo, Hokkaido, 003-0804
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Suita, Osaka, 565 0871
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Yokohama, Kanagawa, 241-8515
China10 sites
Novartis Investigative Site
Beijing, 100039
Novartis Investigative Site
Changsha, Hunan, 410013
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Chengdu, Sichuan, 610041
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Guangzhou, 510060
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Hangzhou, Zhejiang, 310022
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Harbin, Heilongjiang, 150081
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Nanjing, Jiangsu, 210009
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Shanghai, Shanghai Municipality, 200032
Novartis Investigative Site
Shanghai, 200025
Novartis Investigative Site
Shengyang, Liaoning, 110042
United Kingdom9 sites
Novartis Investigative Site
Bournemouth, BH7 7DW
Novartis Investigative Site
Derby, DE22 3NE
Novartis Investigative Site
Leicester, LE1 5WW
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Liverpool, L7 8XP
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London, SE1 9RT
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London, WC1E 6HX
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Manchester, M20 2BX
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Oxford, OX3 7LJ
Novartis Investigative Site
Truro, Cornwall, TR1 3LJ
Australia7 sites
Novartis Investigative Site
Clayton, Victoria, 3168
Novartis Investigative Site
Melbourne, Victoria, 3000
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Murdoch, Western Australia, 6150
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Nedlands, Western Australia, 6009
Novartis Investigative Site
South Brisbane, Queensland, 4101
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Sydney, New South Wales, 2060
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Woollongong, New South Wales, 2500
Belgium7 sites
Novartis Investigative Site
Brussels, 1000
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Charleroi, 6000
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Jette, Brussels Capital, 1090
Novartis Investigative Site
Leuven, 3000
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Liège, 4000
Novartis Investigative Site
Namur, 5000
Novartis Investigative Site
Wilrijk, 2610
Brazil7 sites
Novartis Investigative Site
Barretos, São Paulo, 14784 400
Novartis Investigative Site
Belo Horizonte, Minas Gerais, 30150-270
Novartis Investigative Site
Curitiba, Paraná, 81520-060
Novartis Investigative Site
Ijuí, Rio Grande do Sul, 98700-000
Novartis Investigative Site
Natal, Rio Grande do Norte, 59075 740
Novartis Investigative Site
São Paulo, São Paulo, 01246 000
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Sorocaba, São Paulo
Israel5 sites
Novartis Investigative Site
Haifa, 3525408
Novartis Investigative Site
Jerusalem, 91120
Novartis Investigative Site
Petah Tikva, 49100
Novartis Investigative Site
Ramat Gan, 52621
Novartis Investigative Site
Tel Aviv, 6423906
Russia5 sites
Novartis Investigative Site
Moscow, 115478
Novartis Investigative Site
Moscow, 115998
Novartis Investigative Site
Nizhny Novgorod, 603081
Novartis Investigative Site
Saint Petersburg, 197022
Novartis Investigative Site
Saint Petersburg, 197758
South Korea5 sites
Novartis Investigative Site
Seoul, Seocho Gu, 06591
Novartis Investigative Site
Seoul, 03080
Novartis Investigative Site
Seoul, 03722
Novartis Investigative Site
Seoul, 06351
Novartis Investigative Site
Suwon, Gyeonggi-do, 443380
Taiwan5 sites
Novartis Investigative Site
Kaohsiung City, 80756
Novartis Investigative Site
Kaohsiung City, 833
Novartis Investigative Site
Taichung, 40447
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Taipei, 10048
Novartis Investigative Site
Taipei, 112
Argentina4 sites
Novartis Investigative Site
CABA, Buenos Aires, C1050AAK
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Mar del Plata, Buenos Aires, B7600CTO
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Rio Negro, Viedma, 8500
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San Miguel de Tucumán, Tucumán Province, T4000IAK
Greece4 sites
Novartis Investigative Site
Athens, 115 28
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Heraklion Crete, Greece, 711 10
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Pátrai, 265 00
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Thessaloniki, GR, 54645
Hungary4 sites
Novartis Investigative Site
Budapest, H 1122
Novartis Investigative Site
Debrecen, 4032
Novartis Investigative Site
Miskolc, 3526
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Szolnok, H-5000
Austria3 sites
Novartis Investigative Site
Linz, 4010
Novartis Investigative Site
Salzburg, 5020
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Vienna, A-1090
Czechia3 sites
Novartis Investigative Site
Brno, 65653
Novartis Investigative Site
Brno-Bohunice, Czech Republic, 625 00
Novartis Investigative Site
Olomouc, CZE, 775 20
Poland3 sites
Novartis Investigative Site
Krakow
Novartis Investigative Site
Olsztyn, 10-513
Novartis Investigative Site
Warsaw, 02-776
Switzerland3 sites
Novartis Investigative Site
Bellinzona, 6500
Novartis Investigative Site
Geneva, 1211
Novartis Investigative Site
Zurich, 8038
Thailand3 sites
Novartis Investigative Site
Bangkok, 10330
Novartis Investigative Site
Bangkok, 10400
Novartis Investigative Site
Bangkok, 10700
Slovakia2 sites
Novartis Investigative Site
Bratislava, Slovak Republic, 83310
Novartis Investigative Site
Košice, 041 91
South Africa2 sites
Novartis Investigative Site
Johannesburg, 2196
Novartis Investigative Site
Parktown, 2193
About this study
Official title: A Phase III Randomized, Double Blind Placebo Controlled Study of BKM120 With Fulvestrant, in Postmenopausal Women With Hormone Receptor-positive HER2-negative Locally Advanced or Metastatic Breast Cancer Which Progressed on or After Aromatase Inhibitor Treatment
This study was a multi-center, randomized, double-blind, placebo controlled Phase III study to determine the efficacy and safety of treatment with buparlisib plus fulvestrant versus fulvestrant plus placebo in postmenopausal women with hormone Receptor-positive (HR-positive), human epidermal growth factor receptor 2-negative (HER2-negative), locally advanced or metastatic breast cancer (MBC) whose disease has progressed on or after aromatase inhibitor (AI) treatment.
Read the detailed description
Patients were randomized (1:1) to receive buparlisib (100 mg/day) or placebo with fulvestrant (500 mg); randomization was stratified by PI3K pathway activation status (activated, non-activated, unknown determined in archival tumor tissue) and visceral disease status (present or absent). Tumor evaluation was performed 6 weeks after the randomization date and then every 8 weeks until radiological progression (based on Response Evaluation Criteria In Solid Tumors [RECIST] version 1.1).
Novartis made the decision not to pursue further development of buparlisib and to terminate the ongoing studies in the program. Accordingly, on 19-Dec-2016, Novartis notified all the Investigators about the decision not to pursue further development of buparlisib in Breast Cancer. As a result, the CBKM120F2302 study was terminated on 19-Apr-2019 (last subject last visit).
- Conditions
- Breast Cancer
- Being tested
- Fulvestrant, BKM120, BKM120 matching placebo
- Keywords
- Breast cancer, Hormone receptor positive, HER2-negative, Metastatic, Locally advanced, PI3K, Fulvestrant, Refractory, Aromatase inhibitor
- Medical subject headings
- Breast Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FulvestrantDrug
Intramuscular fulvestrant 500 mg (Day 1 and Day 15 of Cycle 1 and Day 1 of every cycle thereafter)
BKM120Drug
BKM120 100 mg once daily
BKM120 matching placeboDrug
BKM120 matching placebo, once daily
| Study group | Role | What they receive |
|---|---|---|
| BKM120 100mg + Fulvestrant | Experimental | BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol. Receives: Drug: Fulvestrant; Drug: BKM120 |
| Placebo + Fulvestrant | Placebo comparator | BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol. Receives: Drug: Fulvestrant; Drug: BKM120 matching placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival (PFS) Based on Local Investigator Assessment - Full Analysis Set (FAS) in Full Population, Main Study Cohort and PI3K Unknown Cohort
Progression Free Survival (PFS) is defined as the time from date of randomization to the date of first radiologically documented progression or death due to any cause. If a patient did not progress or die at the time of the analysis data cut-off or start of new antineoplastic therapy, PFS was censored at the date of the last adequate tumor assessment before the earliest of the cut-off date or the start date of additional anti-neoplastic therapy. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria RECIST v1.1, as 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline and/or unequivocal progression of the non-target lesions and/or appearance of a new lesion. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm.
Measured: 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 approximately 4 years
Secondary outcomes (8)
Overall Survival (OS) - Full Analysis Set (FAS) in Full Population, Main Study Cohort and PI3K Unknown Cohort
Overall Survival (OS) is 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 known date patient alive. Patients were followed up for the duration of the study and for an expected average of every 3 months after end of treatment.
Measured: Every 3 months following end of treatment visit, assessed for approximately 5 years
Overall Response Rate (ORR) - Full Analysis Set (FAS) in Full Population, Main Study Cohort and PI3K Unknown Cohort
Overall Response Rate (ORR) is defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR) based on local investigator's assessment according to RECIST 1.1. ORR was analyzed in the full population. Response Evaluation Criteria in Solid Tumors (RECIST v1.1) for target/non target lesions: Complete Response (CR), disappearance of all target/non target lesions (all lymph nodes assigned as non-target lesions must be non-pathological in size (< 10 mm short axis)); Partial response (PR), >=30% decrease in the sum of the longest diameter of target lesions ; Overall Response (OR)= CR+PR. Only descriptive analysis performed.
Measured: From the date of randomization until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately 5 years
Clinical Benefit Rate (CBR) - Full Analysis Set (FAS) in Full Population, Main Study Cohort and PI3K Unknown Cohort
Clinical Benefit Rate (CBR) is defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) or stable disease (SD) or Non-CR/non-PD lasting more than 24 weeks based on local investigator's assessment according to RECIST 1.1. CBR was analyzed in the full population. Only descriptive analysis performed.
Measured: From the date of randomization until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately 5 years
Number of Participants With On-Treatments Adverse Events, Serious Adverse Events and Deaths
Analysis of frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths. Only descriptive analysis performed.
Measured: From first dose of study treatment to 30 days after last dose of study treatment, assessed for approximately 5 years
Plasma Concentration-time Profiles of BKM120 in Combination With Fulvestrant at Cycle 2 Day 1
Plasma samples were collected from the first 200 BKM120-treated patients on Cycle 2 Day 1 (at pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h and 24h [before Cycle 2 Day 2 dose] post-dose). Each cycle is 28 days. Only descriptive analysis performed.
Measured: Cycle2 Day1 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours post-dose). Each cycle is 28 days.
Predose Trough Concentration-time Profile of BKM120 in Combination With Fulvestrant Over Time - Pharmacokinetic Analysis Set (PAS)
Pre-dose samples were collected for trough concentrations at Cycle 2 Day 1, Cycle 2 Day 15 and Cycle 3 Day 1. Each cycle is 28 days. Only descriptive analysis performed.
Measured: Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1. Each cycle is 28 days.
Median Time to Definitive Deterioration of the ECOG Performance Status - Full Analysis Set (FAS)
Time to definitive deterioration of the ECOG PS was defined as the time between the date of randomization and the date of the assessment at which definitive deterioration was seen. Only descriptive analysis performed.
Measured: Up to approx 27 months
Health-related Quality of Life (HRQoL):Time to 10% Definitive Deterioration in the Global Health Status/Quality of Life Per EORTC-QLQ-C30
The global health status/QoL scale score of the QLQ-C30 is identified as the primary PRO variable of interest. Physical Functioning (PF), Emotional Functioning (EF) and Social Functioning (SF) scale scores of the QLQ-C30. The time to definitive 10% deterioration is defined as the time from the randomization date to the date of an event, which is defined as a worsening (decrease) in score by at least 10% compared to baseline, with no later increase above this threshold observed during the course of the study or death due to any cause. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. A high score for a functional scale represents a high /healthy level of functioning, a high score for the global health status / QoL represents a high QoL. Patients were assessed up to approx. 8.3 months. Only descriptive analysis performed.
Measured: Cycle 1 day 1, cycle 1 day 15, 6 weeks after randomisation and then every 8 weeks until end of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2012 (estimated)
- Study start7 Aug 2012
- Primary completion29 Apr 2015
- Study completion19 Apr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,147 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01610284
- Sponsor's protocol ID
- CBKM120F2302
- Other IDs
- 2011-005524-17
- Acronym
- BELLE-2
- Status last verified
- Aug 2020
- First submitted
- 11 May 2012
- Last updated
- 25 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Publications
Campone M, Im SA, Iwata H, Clemons M, Ito Y, Awada A, Chia S, Jagiello-Gruszfeld A, Pistilli B, Tseng LM, Hurvitz S, Masuda N, Cortes J, De Laurentiis M, Arteaga CL, Jiang Z, Jonat W, Le Mouhaer S, Sankaran B, Bourdeau L, El-Hashimy M, Sellami D, Baselga J. Buparlisib plus fulvestrant versus placebo plus fulvestrant for postmenopausal, hormone receptor-positive, human epidermal growth factor receptor 2-negative, advanced breast cancer: Overall survival results from BELLE-2. Eur J Cancer. 2018 Nov;103:147-154. doi: 10.1016/j.ejca.2018.08.002. Epub 2018 Sep 18.
PubMed 30241001Baselga J, Im SA, Iwata H, Cortes J, De Laurentiis M, Jiang Z, Arteaga CL, Jonat W, Clemons M, Ito Y, Awada A, Chia S, Jagiello-Gruszfeld A, Pistilli B, Tseng LM, Hurvitz S, Masuda N, Takahashi M, Vuylsteke P, Hachemi S, Dharan B, Di Tomaso E, Urban P, Massacesi C, Campone M. Buparlisib plus fulvestrant versus placebo plus fulvestrant in postmenopausal, hormone receptor-positive, HER2-negative, advanced breast cancer (BELLE-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Jul;18(7):904-916. doi: 10.1016/S1470-2045(17)30376-5. Epub 2017 May 30.
PubMed 28576675
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Randomized, Double Blind Placebo Controlled Study of BKM120 With Fulvestrant, in Postmenopausal Women With Hormone Receptor-positive HER2-negative Locally Advanced or Metastatic Breast Cancer Which Progressed on or After Aromatase Inhibitor Treatment
- ClinicalTrials.gov ID
- NCT01610284
- Acronym / sponsor ID
- BELLE-2 / CBKM120F2302
- Conditions
- Breast Cancer
- Keywords
- Breast cancer, Hormone receptor positive, HER2-negative, Metastatic, Locally advanced, PI3K, Fulvestrant, Refractory
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,147 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 7 Aug 2012 (actual)
- Primary completion
- 29 Apr 2015 (actual)
- Study completion
- 19 Apr 2019 (actual)
- First posted
- 4 Jun 2012 (estimated)
- Results
- Posted 18 Jun 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study was a multi-center, randomized, double-blind, placebo controlled Phase III study to determine the efficacy and safety of treatment with buparlisib plus fulvestrant versus fulvestrant plus placebo in postmenopausal women with hormone Receptor-positive (HR-positive), human epidermal growth factor receptor 2-negative (HER2-negative), locally advanced or metastatic breast cancer (MBC) whose disease has progressed on or after aromatase inhibitor (AI) treatment.
Detailed description
Patients were randomized (1:1) to receive buparlisib (100 mg/day) or placebo with fulvestrant (500 mg); randomization was stratified by PI3K pathway activation status (activated, non-activated, unknown determined in archival tumor tissue) and visceral disease status (present or absent). Tumor evaluation was performed 6 weeks after the randomization date and then every 8 weeks until radiological progression (based on Response Evaluation Criteria In Solid Tumors [RECIST] version 1.1).
Novartis made the decision not to pursue further development of buparlisib and to terminate the ongoing studies in the program. Accordingly, on 19-Dec-2016, Novartis notified all the Investigators about the decision not to pursue further development of buparlisib in Breast Cancer. As a result, the CBKM120F2302 study was terminated on 19-Apr-2019 (last subject last visit).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| BKM120 100mg + Fulvestrant | Experimental | Drug: Fulvestrant, Drug: BKM120BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol. |
| Placebo + Fulvestrant | Placebo comparator | Drug: Fulvestrant, Drug: BKM120 matching placeboBKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Locally advanced or metastatic breast cancer
- HER2-negative and hormone receptor-positive status (common breast cancer classification tests)
- Postmenopausal woman
- A tumor sample must be shipped to a Novartis designated laboratory for identification of biomarkers (PI3K activation status)
- Progression or recurrence of breast cancer while on or after aromatase inhibitor treatment
Key exclusion criteria (6 listed)
- Previous treatment with PI3K inhibitors, AKT inhibitors, mTOR inhibitor or fulvestrant
- More than one prior chemotherapy line for metastatic disease
- Symptomatic brain metastases
- Increasing or chronic treatment (> 5 days) with corticosteroids or another immunosuppressive agent
- Active heart (cardiac) disease as defined in the protocol
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FulvestrantIntramuscular fulvestrant 500 mg (Day 1 and Day 15 of Cycle 1 and Day 1 of every cycle thereafter) | Drug | BKM120 100mg + Fulvestrant, Placebo + Fulvestrant |
| BKM120BKM120 100 mg once daily | Drug | BKM120 100mg + Fulvestrant |
| BKM120 matching placeboBKM120 matching placebo, once daily | Drug | Placebo + Fulvestrant |
Primary outcome
Progression Free Survival (PFS) Based on Local Investigator Assessment - Full Analysis Set (FAS) in Full Population, Main Study Cohort and PI3K Unknown Cohort
Time frame: 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 approximately 4 years
Progression Free Survival (PFS) is defined as the time from date of randomization to the date of first radiologically documented progression or death due to any cause. If a patient did not progress or die at the time of the analysis data cut-off or start of new antineoplastic therapy, PFS was censored at the date of the last adequate tumor assessment before the earliest of the cut-off date or the start date of additional anti-neoplastic therapy. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria RECIST v1.1, as 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline and/or unequivocal progression of the non-target lesions and/or appearance of a new lesion. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm.
8 secondary outcomes
Overall Survival (OS) - Full Analysis Set (FAS) in Full Population, Main Study Cohort and PI3K Unknown Cohort
Time frame: Every 3 months following end of treatment visit, assessed for approximately 5 years
Overall Response Rate (ORR) - Full Analysis Set (FAS) in Full Population, Main Study Cohort and PI3K Unknown Cohort
Time frame: From the date of randomization until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately 5 years
Clinical Benefit Rate (CBR) - Full Analysis Set (FAS) in Full Population, Main Study Cohort and PI3K Unknown Cohort
Time frame: From the date of randomization until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately 5 years
Number of Participants With On-Treatments Adverse Events, Serious Adverse Events and Deaths
Time frame: From first dose of study treatment to 30 days after last dose of study treatment, assessed for approximately 5 years
Plasma Concentration-time Profiles of BKM120 in Combination With Fulvestrant at Cycle 2 Day 1
Time frame: Cycle2 Day1 (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 24 hours post-dose). Each cycle is 28 days.
Predose Trough Concentration-time Profile of BKM120 in Combination With Fulvestrant Over Time - Pharmacokinetic Analysis Set (PAS)
Time frame: Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1. Each cycle is 28 days.
Median Time to Definitive Deterioration of the ECOG Performance Status - Full Analysis Set (FAS)
Time frame: Up to approx 27 months
Health-related Quality of Life (HRQoL):Time to 10% Definitive Deterioration in the Global Health Status/Quality of Life Per EORTC-QLQ-C30
Time frame: Cycle 1 day 1, cycle 1 day 15, 6 weeks after randomisation and then every 8 weeks until end of treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30241001Campone M, Im SA, Iwata H, Clemons M, Ito Y, Awada A, Chia S, Jagiello-Gruszfeld A, Pistilli B, Tseng LM, Hurvitz S, Masuda N, Cortes J, De Laurentiis M, Arteaga CL, Jiang Z, Jonat W, Le Mouhaer S, Sankaran B, Bourdeau L, El-Hashimy M, Sellami D, Baselga J. Buparlisib plus fulvestrant versus placebo plus fulvestrant for postmenopausal, hormone receptor-positive, human epidermal growth factor receptor 2-negative, advanced breast cancer: Overall survival results from BELLE-2. Eur J Cancer. 2018 Nov;103:147-154. doi: 10.1016/j.ejca.2018.08.002. Epub 2018 Sep 18.
- Derived from this study: PubMed 28576675Baselga J, Im SA, Iwata H, Cortes J, De Laurentiis M, Jiang Z, Arteaga CL, Jonat W, Clemons M, Ito Y, Awada A, Chia S, Jagiello-Gruszfeld A, Pistilli B, Tseng LM, Hurvitz S, Masuda N, Takahashi M, Vuylsteke P, Hachemi S, Dharan B, Di Tomaso E, Urban P, Massacesi C, Campone M. Buparlisib plus fulvestrant versus placebo plus fulvestrant in postmenopausal, hormone receptor-positive, HER2-negative, advanced breast cancer (BELLE-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Jul;18(7):904-916. doi: 10.1016/S1470-2045(17)30376-5. Epub 2017 May 30.
- Individual participant dataSharing planned: Yes. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
268 sites in 29 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Fulvestrant and BKM120 in people with Breast Cancer, run by Novartis Pharmaceuticals at 268 sites in 29 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 268 sites in United States, Spain, Italy, France, Germany and 24 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival (PFS) Based on Local Investigator Assessment - Full Analysis Set (FAS) in Full Population, Main Study Cohort and PI3K Unknown Cohort (time frame: 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 approximately 4 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01610284, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2020.