Study to Assess the Safety and Efficacy of Ribociclib (LEE011) in Combination With Letrozole for the Treatment of Men and Pre/Postmenopausal Women With HR+ HER2- aBC (COMPLEEMENT-1)

COMPLEEMENT-1: An Open-label, Multicenter, Phase IIIb Study to Assess the Safety and Efficacy of Ribociclib (LEE011) in Combination With Letrozole for the Treatment of Men and Pre/Postmenopausal Women With Hormone Receptor-positive (HR+) HER2-negative (HER2-) Advanced Breast Cancer (aBC) With no Prior Hormonal Therapy for Advanced Disease

The purpose of this study is to collect additional safety and efficacy data for the combination of ribociclib + letrozole in men and pre/postmenopausal women with HR+HER2- advanced breast cancer and no prior hormonal treatment for advanced disease..

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Ribociclib; Drug: Letrozole; Drug: Goserelin; Drug: Leuprolide

Detailed Description

This was an open-label, single arm, multi-center Phase IIIb study. The study was composed of 2 phases: Core Phase and Extension Phase. In the Core Phase, safety and efficacy data was collected. The study treatment during the Core Phase was provided until disease progression, death, unacceptable toxicities, physician's decision, subject/guardian's decision, protocol deviation, study termination by sponsor, lost to follow-up, technical problems or up to 18 months after LPFV.

In the event that patients were still deriving benefit at the end of the Core phase and ribociclib was not approved or available and reimbursed, patients were transitioned to the Extension Phase and continued to receive study treatment until progression, intolerance, death or physician/patient decision. Only safety and clinical benefit (as assessed by investigator) data was collected in the Extension Phase. During the Extension Phase, if ribociclib became locally approved and reimbursed, patients were to be transitioned to prescription. Patients who completed the Extension Phase and continued to derive clinical benefit from the treatment based on the investigator's evaluation received ribociclib from prescription (if approved and reimbursed), another post-trial access program, or other drug access/support program(s).

Canadian sub-study: this sub-study was a multicenter Canadian exploratory correlative sample collection sub-study that aimed to better understand mechanisms of response and resistance to ribociclib in combination with letrozole therapy. This sub-study was available for all Canadian subjects enrolled on the main study and did not alter the planned treatment.

• Study Type: Interventional
• Enrollment (Actual): 3246
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • La Rioja, Argentina, 5300
    • Novartis Investigative Site
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1426ANZ
      • Novartis Investigative Site
    • Caba, Buenos Aires, Argentina, C1125ABD
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  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2000KZE
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  • Tucuman
    • San Miguel De Tucuman, Tucuman, Argentina, T4000IAK
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• Austria
  • Graz, Austria, 8036
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  • Leoben, Austria, A 8700
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  • Rankweil, Austria, A-6830
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  • Salzburg, Austria, 5020
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  • Vienna, Austria, 1090
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  • Vienna, Austria, A 1090
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  • Wien, Austria, A-1130
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  • Tyrol
    • Innsbruck, Tyrol, Austria, 6020
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• Belgium
  • Antwerp, Belgium, 2020
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  • Bonheiden, Belgium, 2820
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  • Brugge, Belgium, 8000
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  • Brussel, Belgium, 1090
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  • Brussels, Belgium, BE-B-1200
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  • Bruxelles, Belgium, 1000
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  • Charleroi, Belgium, 6000
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  • Genk, Belgium, 3600
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  • Gent, Belgium, 9000
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  • Hasselt, Belgium, 3500
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  • Kortrijk, Belgium, 8500
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  • Leuven, Belgium, 3000
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  • Liege, Belgium, 4000
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  • Luxembourg, Belgium, 1210
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  • Mons, Belgium, 7000
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  • Namur, Belgium, 5000
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  • Roeselare, Belgium, 8800
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  • Verviers, Belgium, 4800
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  • Wilrijk, Belgium, 2610
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  • Oost Vlaanderen
    • Sint Niklaas, Oost Vlaanderen, Belgium, 9100
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• Bulgaria
  • Gabrovo, Bulgaria, 5300
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  • Plovdiv, Bulgaria, 4004
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  • Sofia, Bulgaria, 1527
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  • Sofia, Bulgaria, 1756
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  • Sofia, Bulgaria, 1606
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  • Sofia, Bulgaria, 1303
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• Canada
  • Quebec, Canada, G1S 4L8
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  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
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    • Edmonton, Alberta, Canada, T6G 1Z2
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  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 5L3
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    • Surrey, British Columbia, Canada, V3V 1Z2
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    • Vancouver, British Columbia, Canada, V5Z 4E6
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  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
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  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 6Z8
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  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
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  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
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    • Cambridge, Ontario, Canada, N1R 3G2
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    • Hamilton, Ontario, Canada, L8V 5C2
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    • Kingston, Ontario, Canada, K7L 5P9
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    • Kitchener, Ontario, Canada, N2G 1G3
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    • London, Ontario, Canada, N6A 4G4
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    • Oshawa, Ontario, Canada, L1G 2B9
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    • Ottawa, Ontario, Canada, KIH 7W9
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    • Sault Ste Marie, Ontario, Canada, P6B 0A8
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  • Saskatchewan
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• Chile
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• Czechia
  • Brno, Czechia, 625 00
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  • Ceske Budejovice, Czechia, 370 87
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  • Praha, Czechia, 12808
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    • Olomouc, CZE, Czechia, 779 00
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  • Czech Republic
    • Brno, Czech Republic, Czechia, 656 53
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    • Liberec, Czech Republic, Czechia, 46063
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    • Prague 8, Czech Republic, Czechia, 180 00
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    • Zlin, Czech Republic, Czechia, 762 75
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• Denmark
  • Copenhagen, Denmark, DK-2100
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  • Vejle, Denmark, 7100
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• Finland
  • Helsinki, Finland, 00029
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  • Oulu, Finland, FIN-90220
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  • Tampere, Finland, FIN-33521
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• France
  • Albi, France, 81000
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  • Angers Cedex 02, France, 49055
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  • Bordeaux, France, 33076
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  • Bordeaux Cedex, France, 33000
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  • Caen, France, 14021
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  • Clermont-Ferrand, France, 63011
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  • Colmar Cedex, France, 68024
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  • Corbeil Essonnes, France, 91100
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  • Creteil, France, 94010
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  • Le Mans Cedex, France, 72015
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  • Lille Cedex, France, 59020
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  • Limoges, France, 87000
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  • Lyon, France, 69373
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  • Lyon Cedex 08, France, 69373
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  • Marseille, France, 13273
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  • Mont de Marsan cedex, France, 40024
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  • Montpellier, France, 34070
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  • Montpellier, France, 34298
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  • Nancy, France, 54000
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  • Nantes Cedex, France, 44277
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  • Paris, France, 75231
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  • Paris, France, 75970
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  • Paris, France, 75012
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  • Paris 10, France, 75475
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  • Paris 13, France, 75651
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  • Perigueux Cedex, France, 24004
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  • Pierre Benite, France, 69495
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  • Plerin Sur Mer, France, 22190
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  • Reims, France, 51100
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  • Rouen, France, 76038
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  • Saint Herblain, France, 44805
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  • Strasbourg, France, 67010
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  • Strasbourg Cedex, France, 67091
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  • Troyes, France, 10003
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  • Vandoeuvre-les-Nancy, France, 54519
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  • Alpes Maritimes
    • Nice Cedex 2, Alpes Maritimes, France, 06189
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  • Cote D Or
    • Dijon, Cote D Or, France, 21034
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  • Haute Vienne
    • Limoges, Haute Vienne, France, 87000
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  • Hauts De Seine
    • Saint-Cloud, Hauts De Seine, France, 92210
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  • Indre Et Loire
    • Tours 9, Indre Et Loire, France, 37044
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  • Marne
    • Reims, Marne, France, 51056
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• Greece
  • Athens, Greece, 115 28
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  • Athens, Greece, GR 115 22
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  • Athens, Greece, GR14564
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  • Patras, Greece, 265 00
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  • Thessaloniki, Greece, 540 07
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  • GR
    • Ioannina, GR, Greece, 455 00
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    • Thessaloniki, GR, Greece, 54645
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• Hong Kong
  • Hong Kong, Hong Kong
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  • Pokfulam, Hong Kong
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• Hungary
  • Budapest, Hungary, H 1122
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  • Budapest, Hungary, 1134
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  • Budapest, Hungary, H-1032
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  • Debrecen, Hungary, 4032
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  • Szeged, Hungary, 6725
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• India
  • Delhi, India, 110 085
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  • Andhra Pradesh
    • Hyderabad, Andhra Pradesh, India, 500 034
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  • Chennai
    • Tamil Nadu, Chennai, India, 600035
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  • Delhi
    • New Delhi, Delhi, India, 110092
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  • Gujarat
    • Admedabad, Gujarat, India, 380060
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  • Karnataka
    • Bangalore, Karnataka, India, 560027
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  • Maharashtra
    • Nashik, Maharashtra, India, 422 004
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    • Pune, Maharashtra, India, 411013
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  • Rajasthan
    • Jaipur, Rajasthan, India, 302017
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  • Tamil Nadu
    • Vellore, Tamil Nadu, India, 632 004
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  • West Bengal
    • Kolkata, West Bengal, India, 700160
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• Israel
  • Beer-Sheva, Israel, 8457108
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  • Haifa, Israel, 3109601
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  • Petach Tikva, Israel, 4941492
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  • Ramat Gan, Israel, 52621
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  • Tel Aviv, Israel, 6423906
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• Italy
  • Napoli, Italy, 80131
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  • Napoli, Italy, 80138
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  • Novara, Italy, 28100
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  • AL
    • Alessandria, AL, Italy, 15100
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  • AN
    • Ancona, AN, Italy, 60126
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  • AQ
    • L'Aquila, AQ, Italy, 67100
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  • AR
    • Arezzo, AR, Italy, 52100
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  • AT
    • Asti, AT, Italy, 14100
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  • AV
    • Avellino, AV, Italy, 83100
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  • BA
    • Bari, BA, Italy, 70124
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  • BG
    • Bergamo, BG, Italy, 24127
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    • Treviglio, BG, Italy, 24047
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  • BN
    • Benevento, BN, Italy, 82100
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  • BO
    • Bologna, BO, Italy, 40138
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    • Bologna, BO, Italy, 40139
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  • BR
    • Brindisi, BR, Italy, 72100
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  • BS
    • Brescia, BS, Italy, 25123
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    • Brescia, BS, Italy, 25124
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  • CA
    • Monserrato, CA, Italy, 09042
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    • Cuneo, CN, Italy, 12100
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  • CR
    • Cremona, CR, Italy, 26100
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  • CT
    • Catania, CT, Italy, 95124
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  • FE
    • Cona, FE, Italy, 44100
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    • San Giovanni Rotondo, FG, Italy, 71013
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    • Firenze, FI, Italy, 50134
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    • Genova, GE, Italy, 16132
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    • Grosseto, GR, Italy, 58100
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    • Livorno, LI, Italy, 57124
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    • Lucca, LU, Italy, 55100
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    • Monza, MB, Italy, 20900
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    • Macerata, MC, Italy, 62100
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    • Messina, ME, Italy, 98158
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    • Taormina, ME, Italy, 98039
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    • Milano, MI, Italy, 20162
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    • Modena, MO, Italy, 41124
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    • Nuoro, NU, Italy, 08100
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    • Palermo, PA, Italy, 90127
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    • Fano, PU, Italy, 61032
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    • Reggio Calabria, RC, Italy, 89124
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    • Reggio Emilia, RE, Italy, 42123
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    • Roma, RM, Italy, 00168
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    • Salerno, SA, Italy, 84131
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    • Sassari, SS, Italy, 07100
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    • Savona, SV, Italy, 17100
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    • Trento, TN, Italy, 38100
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    • Candiolo, TO, Italy, 10060
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• Jordan
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• Lebanon
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• Malaysia
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• Mexico
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• Netherlands
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• Norway
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• Oman
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• Panama
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• Philippines
  • Las Pinas, Philippines, 1740
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  • Metro Manila
    • Taguig City, Metro Manila, Philippines, 1634
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• Poland
  • Bydgoszcz, Poland, 85 796
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  • Bytom, Poland, 41-902
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  • Gdansk, Poland, 80 952
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  • Lublin, Poland, 20 090
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  • Opole, Poland, 45-061
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  • Rzeszow, Poland, 35-021
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  • Warszawa, Poland, 02 781
    • Novartis Investigative Site
  • Wroclaw, Poland, 53 413
    • Novartis Investigative Site
  • Slaskie
    • Zory, Slaskie, Poland, 44-240
      • Novartis Investigative Site
• Portugal
  • Braga, Portugal, 4710243
    • Novartis Investigative Site
  • Guimaraes, Portugal, 4835-044
    • Novartis Investigative Site
  • Lisboa, Portugal, 1649-035
    • Novartis Investigative Site
  • Lisboa, Portugal, 1500 650
    • Novartis Investigative Site
  • Lisboa, Portugal, 1400-038
    • Novartis Investigative Site
  • Lisboa, Portugal, 1998-018
    • Novartis Investigative Site
  • Porto, Portugal, 4099-001
    • Novartis Investigative Site
  • Porto, Portugal, 4200-319
    • Novartis Investigative Site
  • Porto, Portugal, 4200-072
    • Novartis Investigative Site
• Russian Federation
  • Chelyabinsk, Russian Federation, 454087
    • Novartis Investigative Site
  • Irkutsk, Russian Federation, 664035
    • Novartis Investigative Site
  • Kaluga, Russian Federation, 248007
    • Novartis Investigative Site
  • Krasnoyarsk, Russian Federation, 660022
    • Novartis Investigative Site
  • Moscow, Russian Federation, 115478
    • Novartis Investigative Site
  • Moscow, Russian Federation, 125284
    • Novartis Investigative Site
  • Moscow Region Istra Village, Russian Federation, 143423
    • Novartis Investigative Site
  • Moscow Rerion Balashiha, Russian Federation, 143900
    • Novartis Investigative Site
  • Rostov-na-Donu, Russian Federation, 344037
    • Novartis Investigative Site
  • Samara, Russian Federation, 443031
    • Novartis Investigative Site
  • St Petersburg, Russian Federation, 197758
    • Novartis Investigative Site
  • St Petersburg, Russian Federation, 197022
    • Novartis Investigative Site
  • Ufa, Russian Federation, 450054
    • Novartis Investigative Site
  • Yaroslavl, Russian Federation, 150054
    • Novartis Investigative Site
  • Russia
    • Leningrad Region, Russia, Russian Federation, 188663
      • Novartis Investigative Site
  • Tatarstan Republic
    • Kazan, Tatarstan Republic, Russian Federation, 420029
      • Novartis Investigative Site
• Saudi Arabia
  • Dammam, Saudi Arabia, 15215
    • Novartis Investigative Site
  • Makkah, Saudi Arabia, 57657
    • Novartis Investigative Site
  • Riyadh, Saudi Arabia, 11211
    • Novartis Investigative Site
  • Riyadh, Saudi Arabia, 11426
    • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 308433
    • Novartis Investigative Site
  • Singapore, Singapore, 217562
    • Novartis Investigative Site
  • Singapore, Singapore, 258500
    • Novartis Investigative Site
• Slovakia
  • Kosice, Slovakia, 04191
    • Novartis Investigative Site
  • Poprad, Slovakia, 058 01
    • Novartis Investigative Site
  • Slovak Republic
    • Banska Bystrica, Slovak Republic, Slovakia, 97401
      • Novartis Investigative Site
• Slovenia
  • Ljubljana, Slovenia, 1000
    • Novartis Investigative Site
  • Maribor, Slovenia, 2000
    • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08041
    • Novartis Investigative Site
  • Burgos, Spain, 09006
    • Novartis Investigative Site
  • Granollers, Spain, 08402
    • Novartis Investigative Site
  • Madrid, Spain, 28041
    • Novartis Investigative Site
  • Madrid, Spain, 28034
    • Novartis Investigative Site
  • Madrid, Spain, 28046
    • Novartis Investigative Site
  • Madrid, Spain, 28006
    • Novartis Investigative Site
  • Madrid, Spain, 28040
    • Novartis Investigative Site
  • Madrid, Spain, 28009
    • Novartis Investigative Site
  • Madrid, Spain, 28222
    • Novartis Investigative Site
  • Murcia, Spain, 30008
    • Novartis Investigative Site
  • Valencia, Spain, 46026
    • Novartis Investigative Site
  • Zaragoza, Spain, 50009
    • Novartis Investigative Site
  • Alicante
    • Elche, Alicante, Spain, 03203
      • Novartis Investigative Site
  • Andalucia
    • Almeria, Andalucia, Spain, 04009
      • Novartis Investigative Site
    • Cordoba, Andalucia, Spain, 14004
      • Novartis Investigative Site
    • Granada, Andalucia, Spain, 18014
      • Novartis Investigative Site
    • Huelva, Andalucia, Spain, 21005
      • Novartis Investigative Site
    • Jaen, Andalucia, Spain, 23007
      • Novartis Investigative Site
    • Malaga, Andalucia, Spain, 29010
      • Novartis Investigative Site
    • Sevilla, Andalucia, Spain, 41013
      • Novartis Investigative Site
    • Sevilla, Andalucia, Spain, 41009
      • Novartis Investigative Site
    • Sevilla, Andalucia, Spain, 41014
      • Novartis Investigative Site
  • Barcelona
    • Sabadell, Barcelona, Spain, 08208
      • Novartis Investigative Site
  • Cadiz
    • Jerez, Cadiz, Spain, 11407
      • Novartis Investigative Site
  • Castilla La Mancha
    • Toledo, Castilla La Mancha, Spain, 45071
      • Novartis Investigative Site
  • Castilla Y Leon
    • Salamanca, Castilla Y Leon, Spain, 37007
      • Novartis Investigative Site
  • Cataluna
    • Barcelona, Cataluna, Spain, 08024
      • Novartis Investigative Site
    • Lerida, Cataluna, Spain, 25198
      • Novartis Investigative Site
  • Catalunya
    • Badalona, Catalunya, Spain, 08916
      • Novartis Investigative Site
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
    • Barcelona, Catalunya, Spain, 08036
      • Novartis Investigative Site
    • Girona, Catalunya, Spain, 17007
      • Novartis Investigative Site
    • Hospitalet de LLobregat, Catalunya, Spain, 08907
      • Novartis Investigative Site
  • Comunidad Valenciana
    • Alicante, Comunidad Valenciana, Spain, 03010
      • Novartis Investigative Site
    • Alicante, Comunidad Valenciana, Spain, 03550
      • Novartis Investigative Site
    • Castellon, Comunidad Valenciana, Spain, 12002
      • Novartis Investigative Site
    • Valencia, Comunidad Valenciana, Spain, 46014
      • Novartis Investigative Site
    • Valencia, Comunidad Valenciana, Spain, 46010
      • Novartis Investigative Site
    • Valencia, Comunidad Valenciana, Spain, 46009
      • Novartis Investigative Site
    • Valencia, Comunidad Valenciana, Spain, 46015
      • Novartis Investigative Site
  • Extremadura
    • Badajoz, Extremadura, Spain, 06080
      • Novartis Investigative Site
    • Caceres, Extremadura, Spain, 10003
      • Novartis Investigative Site
  • Galicia
    • La Coruna, Galicia, Spain, 15006
      • Novartis Investigative Site
    • Santiago de Compostela, Galicia, Spain, 15706
      • Novartis Investigative Site
  • Islas Baleares
    • Palma De Mallorca, Islas Baleares, Spain, 07120
      • Novartis Investigative Site
  • Las Palmas De Gran Canaria
    • Las Palmas De Gran Canarias, Las Palmas De Gran Canaria, Spain, 35016
      • Novartis Investigative Site
  • Murcia
    • El Palmar, Murcia, Spain, 30120
      • Novartis Investigative Site
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Novartis Investigative Site
  • Pais Vasco
    • Bilbao, Pais Vasco, Spain, 48013
      • Novartis Investigative Site
    • San Sebastian, Pais Vasco, Spain, 20080
      • Novartis Investigative Site
  • Pontevedra
    • Vigo, Pontevedra, Spain, 36212
      • Novartis Investigative Site
  • Santa Cruz De Tenerife
    • La Laguna, Santa Cruz De Tenerife, Spain, 38320
      • Novartis Investigative Site
  • Tarragona
    • Reus, Tarragona, Spain, 43201
      • Novartis Investigative Site
• Sweden
  • Gothenburg, Sweden, SE-431 45
    • Novartis Investigative Site
  • Orebro, Sweden, 701 85
    • Novartis Investigative Site
  • Stockholm, Sweden, SE-118 83
    • Novartis Investigative Site
  • Uppsala, Sweden, 751 85
    • Novartis Investigative Site
  • Vaxjo, Sweden, SE-351 85
    • Novartis Investigative Site
• Taiwan
  • Taichung, Taiwan, 40447
    • Novartis Investigative Site
  • Tainan, Taiwan, 70403
    • Novartis Investigative Site
  • Taipei, Taiwan, 114
    • Novartis Investigative Site
• Thailand
  • Bangkok, Thailand, 10400
    • Novartis Investigative Site
  • Chiang Mai, Thailand, 50200
    • Novartis Investigative Site
  • Hat Yai
    • Songkhla, Hat Yai, Thailand, 90110
      • Novartis Investigative Site
  • THA
    • Khon Kaen, THA, Thailand, 40002
      • Novartis Investigative Site
• United Kingdom
  • Bristol, United Kingdom, BS2 8ED
    • Novartis Investigative Site
  • Cardiff, United Kingdom, CF14 2TL
    • Novartis Investigative Site
  • East Sussex, United Kingdom, BN2 5BE
    • Novartis Investigative Site
  • Edinburgh, United Kingdom, EH4 2XU
    • Novartis Investigative Site
  • Exeter, United Kingdom, EX2 5DW
    • Novartis Investigative Site
  • Glasgow, United Kingdom, G12 0YN
    • Novartis Investigative Site
  • Leeds, United Kingdom, LS9 7TF
    • Novartis Investigative Site
  • Leicester, United Kingdom, LE1 5WW
    • Novartis Investigative Site
  • London, United Kingdom, SW3 6JJ
    • Novartis Investigative Site
  • London, United Kingdom, NW1 2PJ
    • Novartis Investigative Site
  • London, United Kingdom, W8 6RF
    • Novartis Investigative Site
  • Manchester, United Kingdom, M20 4BX
    • Novartis Investigative Site
  • Newcastle upon Tyne, United Kingdom, NE7 7DN
    • Novartis Investigative Site
  • Nottingham, United Kingdom, NG5 1PB
    • Novartis Investigative Site
  • Oxford, United Kingdom, OX3 7LJ
    • Novartis Investigative Site
  • Plymouth, United Kingdom, PL6 8DH
    • Novartis Investigative Site
  • Preston, United Kingdom, PR2 9HT
    • Novartis Investigative Site
  • Sheffield, United Kingdom, S10 2SJ
    • Novartis Investigative Site
  • Stoke-on-Trent, United Kingdom, ST4 6QG
    • Novartis Investigative Site
  • Cambridgeshire
    • Peterborough, Cambridgeshire, United Kingdom, PE3 9GZ
      • Novartis Investigative Site
  • Cornwall
    • Truro, Cornwall, United Kingdom, TR1 3LJ
      • Novartis Investigative Site
  • Hants
    • Portsmouth, Hants, United Kingdom, PO6 3LY
      • Novartis Investigative Site
  • Kent
    • Maidstone, Kent, United Kingdom, ME16 9QQ
      • Novartis Investigative Site
  • North Yorkshire
    • York, North Yorkshire, United Kingdom, YO31 8HE
      • Novartis Investigative Site
  • Scotland
    • Aberdeen, Scotland, United Kingdom, AB25 2ZN
      • Novartis Investigative Site
  • Suffolk
    • Ipswich, Suffolk, United Kingdom, IP4 5PD
      • Novartis Investigative Site
  • Surrey
    • Guildford, Surrey, United Kingdom, GU2 7XX
      • Novartis Investigative Site
    • Sutton, Surrey, United Kingdom, SM2 5PT
      • Novartis Investigative Site
• United States
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Alaska Cancer Research and Education Center
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Ironwood Cancer and Research Centers
    • Phoenix, Arizona, United States, 85016
      • Arizona Oncology Associates
    • Tucson, Arizona, United States, 85745
      • Arizona Oncology Associates Arizona Oncology Assoc. (2)
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Highlands Oncology Group
  • California
    • Beverly Hills, California, United States, 90211
      • Beverly Hills Cancer Center
    • Long Beach, California, United States, 90813
      • Pacific Shores Medical Group SC
    • Los Angeles, California, United States, 90033
      • USC Norris Cancer Center
    • Orange, California, United States, 92868
      • University of California Irvine UC Irvine (11)
    • Oxnard, California, United States, 93030
      • Ventura County Hematology and Oncology
    • Pismo Beach, California, United States, 93449
      • PCR Oncology
    • San Francisco, California, United States, 94120-7999
      • California Pacific Medical Center Onc Dept
  • Colorado
    • Denver, Colorado, United States, 80210
      • Centura Health Research Center Centura Health Research Center
    • Fort Collins, Colorado, United States, 80528
      • Poudre Valley Hospital Poudre Valley Health System
    • Glenwood Springs, Colorado, United States, 81601
      • Valley View Hospital Cancer Center
  • Florida
    • Davie, Florida, United States, 33328
      • Florida Cancer Research Institute Dept of Oncology
    • Hollywood, Florida, United States, 33021
      • Foundation for Sickle Cell Disease Research
    • Lakeland, Florida, United States, 33805
      • Watson Clinic Center for Research 1730 Location
    • Orange, Florida, United States, 32763
      • Mid Florida Hematology And Onc Ctr
  • Georgia
    • Savannah, Georgia, United States, 31405
      • Summit Cancer Care Summit Cancer Care (SC)
    • Thomasville, Georgia, United States, 31792
      • John D Archbold Memorial Hospital John D. Archbold Mem Hosp (4)
  • Idaho
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Regional Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Stroger Cook County Hospital Division of Hematology & Onc
    • Joliet, Illinois, United States, 60435
      • Joliet Oncology-Hematology Associates Presence Cancer Center
    • Normal, Illinois, United States, 61761
      • Mid Illinois Hematology Oncology Mid Illinois Hema/Onc (3)
    • Tinley Park, Illinois, United States, 60487
      • Alpha Med Physician Group, LLC
  • Indiana
    • Goshen, Indiana, United States, 46526
      • Indian Univ Health Goshen Center forCancer SC
    • Munster, Indiana, United States, 46321
      • Northwest Oncology
  • Iowa
    • Sioux City, Iowa, United States, 51101
      • June E. Nylan Cancer Center
  • Kansas
    • Kansas City, Kansas, United States, 66160-7330
      • University of Kansas Medical Center University of Kansas Med Ctr 9
    • Overland Park, Kansas, United States, 66209
      • Sarah Cannon at Overland Park Regional Medical Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • John Ochsner Heart and Vascular Institute Clinical Trials
  • Maine
    • Portland, Maine, United States, 04102
      • Northern Light Mercy Hospital SC
  • Maryland
    • Baltimore, Maryland, United States, 21204-6831
      • Greater Baltimore Medical Center Cancer Center Greater Baltimore Medical Ctr
    • Rockville, Maryland, United States, 20879
      • Kaiser Permanente
    • Rockville, Maryland, United States, 20850
      • Maryland Oncology Hematology P A Columbia
    • Washington DC, Maryland, United States, 20037
      • Medical Faculty Assc Inc Medical Faculty Assc., Inc. (2
  • Mississippi
    • Jackson, Mississippi, United States, 39202
      • Jackson Oncology Associates
  • Nebraska
    • Lincoln, Nebraska, United States, 68506
      • Nebraska Hematology-Oncology, P.C.
    • Omaha, Nebraska, United States, 68154
      • Nebraska Cancer Specialists Oncology Hematology West
  • Nevada
    • Henderson, Nevada, United States, 89052
      • Comprehensive Cancer Centers of Nevada CCC of Nevada Henderson (4)
  • New Jersey
    • Elizabeth, New Jersey, United States, 07207
      • Trinitas Comprehensive Cancer Center
    • Englewood, New Jersey, United States, 07631
      • Englewood Health
    • Paramus, New Jersey, United States, 07652
      • The Valley Hospital / Luckow Pavillion
    • Somerset, New Jersey, United States, 08873
      • Somerset Hematology Oncology Associates Somerset Hematolgy Onc -MI
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • New Mexico Cancer Care Alliance .
    • Farmington, New Mexico, United States, 87401
      • San Juan Oncology Associates
  • New York
    • Bronx, New York, United States, 10469
      • Eastchester Center for Cancer Care
    • Lake Success, New York, United States, 11042
      • Clinical Research Alliance
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Oncology Speciialists of Charlotte
  • Ohio
    • Canton, Ohio, United States, 44710
      • Aultman Cancer Center Main Centre
    • Cincinnati, Ohio, United States, 45219
      • The Christ Hospital Cancer Center Research Program Linder Research Center
    • Cleveland, Ohio, United States, 44106
      • University Hospitals of Cleveland Seidman Cancer Center Cleveland Medical Center
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation Cleveland Clinic (5)
    • Kettering, Ohio, United States, 45409
      • Dayton Physicians
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Oklahoma Cancer Specialists and Research Institute SC-2
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health Sciences University SC-5
  • South Carolina
    • Florence, South Carolina, United States, 29506
      • McLeod Center for Cancer Treatment and Research
    • Rock Hill, South Carolina, United States, 29732
      • Carolina Blood and Cancer Care of South Carolina
  • Texas
    • Houston, Texas, United States, 77090
      • Millennium Research Clin Develop Millennium Oncology - FL
    • San Antonio, Texas, United States, 78229
      • Mays Cancer Ctr Uthsa Mdacc
    • Tyler, Texas, United States, 75701
      • HOPE Cancer Center of East Texas
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Virginia Oncology Associates
  • Washington
    • Bellingham, Washington, United States, 98225
      • PeaceHealth St Joseph Medical Center
    • Everett, Washington, United States, 98201
      • Providence Regional Medical Centre of Everett
    • Kennewick, Washington, United States, 99336
      • Kadlec Clinic Hematology and Onco
    • Renton, Washington, United States, 98055
      • Valley Medical Center Research Valley Medical Center
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center-Oncology SC
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties Dept.ofNW Med. Specialties
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53211
      • Columbia St Mary s Hospital of Milwaukee St. Mary's Hospital Ozaukee
  • Wyoming
    • Cheyenne, Wyoming, United States, 82001
      • Cheyenne Regional Medical Center Cheyenne Regional Med Ctr (3)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Male or female advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative therapy.

• In the case of women, both pre/perimenopausal and postmenopausal patients were allowed to be included in this study; menopausal status was relevant for the requirement of goserelin to be used concomitantly with ribociclib and letrozole.

  1. Postmenopausal status was defined either by: I).Prior bilateral oophorectomy OR ii). Age ≥ 60 OR iii). Age < 60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifen, or ovarian suppression) and FSH and estradiol in the postmenopausal range per local normal range. If patient was taking tamoxifen or toremifene and age < 60, then FSH and plasma estradiol levels would be in post-menopausal range per local normal range (NCCN Guidelines version 2.2017).

     Note: For women with therapy-induced amenorrhea, serial measurements of FSH and/or estradiol were needed to ensure menopausal status.

  2. Premenopausal status was defined as either: I).Patient had last menstrual period within the last 12 months OR ii). If on tamoxifen or toremifene within the past 14 days, plasma estradiol and FSH must be in the premenopausal range per local normal range OR iii). In case of therapy induced amenorrhea, plasma estradiol and/or FSH must be in the premenopausal range per local normal range.
  3. Perimenopausal status was define as neither premenopausal nor postmenopausal
• Patient had a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer by local laboratory.
• Patient had HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test was required by local laboratory testing.
• Patient had an Eastern Cooperative Oncology Group (ECOG) performance status ≤2

• Patient had adequate bone marrow and organ function as defined by ALL of the following laboratory values (as assessed by local laboratory):

  • Absolute neutrophil count ≥ 1.5 × 10^9/L
  • Platelets ≥ 100 × 10^9/L
  • Hemoglobin ≥ 9.0 g/dL
  • Potassium, sodium, calcium corrected for serum albumin and magnesium within normal limits or corrected to within normal limits with supplements before first dose of the study medication
  • INR ≤1.5
  • Serum creatinine <1.5 mg/dl or creatinine clearance≥50 mL/min
  • In absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) should be below 2.5 × ULN. If the patient had liver metastases, ALT and AST should be < 5 × ULN.
  • Total serum bilirubin < ULN; or total bilirubin ≤ 3.0 × ULN with direct bilirubin within normal range in patients with well-documented Gilbert's Syndrome

• Patient must have had a 12-lead ECG with ALL of the following parameters at screening:

  • QTcF interval at screening <450 msec (using Fridericia's correction)
  • Resting heart rate ≥ 50 bpm

Key Exclusion Criteria:

• Patient who received any CDK4/6 inhibitor

• Patient who received any prior systemic hormonal therapy for advanced breast cancer; no more than one prior regimen of chemotherapy for the treatment of metastatic disease was permitted. Note:

  • Patients who received (neo) adjuvant therapy for breast cancer were eligible. If the prior neo (adjuvant) therapy included letrozole or anastrozole the disease free interval had to be greater than 12 months from the completion of treatment until study entry.
  • Patients who received ≤ 28 days of letrozole or anastrozole for advanced disease prior to inclusion in this trial were eligible.
  • Any prior (neo) adjuvant anti-cancer therapy or prior chemotherapy for metastatic disease had to be stopped at least 5 half-lives or 7 days, whichever was longer, before study inclusion.
• Patient was concurrently using other anti-cancer therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Ribociclib + letrozole+goserelin/leuprolide; Participants received ribociclib (orally taken, 3 weeks on/1 week off) in combination with letrozole (orally taken once daily). For men and premenopausal women, either goserelin was given as an injectable subcutaneous implant or leuprolide was given as an intramuscular injection.

Drug: Ribociclib; Ribociclib was centrally supplied to the investigators and administered orally once a day on days 1-21 of each 28 day cycle at a starting dose of 600 mg daily; Other Names: LEE011; Drug: Letrozole; Letrozole was procured locally and administered orally once a day on a continuous daily schedule at a dose of 2.5 mg; Drug: Goserelin; Goserelin was procured locally and administered in men and premenopausal women as an injectable subcutaneous implant administered on day 1 starting at Cycle 1 and then every 28 days at a dose of 3.6 mg (cycle = 28 days); Drug: Leuprolide; Leuprolide was procured locally and administered in men and premenopausal women as an injectable intramuscular depot administered on day 1 starting at Cycle 1 and then every 28 days at a dose of 7.5 mg (cycle= 28 days)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) During Treatment With Ribociclib + Letrozole in the Core Phase	AEs were defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s). SAEs were defined as meeting at least 1 of the following criteria: is fatal or life-threatening, Results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, is medically significant, requires inpatient hospitalization or prolongation of existing hospitalization. A SAE which caused death of the participant was considered as fatal SAE. AEs were assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Grade 1 to 5 were used to characterize the severity of the Adverse Event. Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening and Grade 5: death related to AE. A participant with multiple severity grades for an AE is only counted under the maximum grade.	From start of treatment up to 30 days after last treatment (for participants who did not enter to the Extension phase) or up to last treatment in the Core phase (for participants who entered the Extension phase), assessed up to approximately 33 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-to-Progression (TTP) Based on Investigator's Assessment (Core Phase)	Time to progression (TTP) is defined as time from date of start of treatment to the date of first documented progression or death due to underlying cancer. Participants with symptoms of rapidly progressing disease without radiologic evidence were classified as progression only when clear evidence of clinical deterioration was documented and/or patient discontinued due to 'Disease progression' or death due to study indication. When there was no documentation of radiologic evidence of progression, and the patient discontinued for 'Disease progression' due to documented clinical deterioration of disease, the date of discontinuation was used as date of progression. TTP was estimated using the Kaplan-Meier method. 95% CI of median was calculated according to Brookmeyer and Crowley method.	Up to approximately 33 months
Overall Response Rate (ORR) Based on Investigator's Assessment (Core Phase)	Overall response rate (ORR) is defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR) according to RECIST 1.1 based on investigator's assessment. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. 95% CI was calculated using the exact binomial method.	Up to approximately 33 months
Clinical Benefit Rate (CBR) Based on Investigator's Assessment (Core Phase)	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 an overall lesion response of stable disease (SD), lasting as per local review, for a duration of at least 24 weeks. CR, PR and SD are defined according to RECIST 1.1 based on investigator's assessment. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease. 95% CI was calculated using the exact binomial method.	Up to approximately 33 months
Change From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Score (Core Phase)	Change from baseline in FACT-B scores was assessed. FACT-B is a self-report instrument that measures multidimensional quality of life (QOL) in patients with breast cancer. The FACT-B consists of 37 questions that address physical, social, emotional, and functional well-being, with specific questions relevant to women with breast cancer. Each item has a score range of 0 (Not at all) to 4 (Very much), with a total score ranging from 0-148. The higher the score, the better the QOL reported by the participant. A positive change from baseline indicates improvement in QoL. Due to the nature of the questionnaire, only females were asked to complete this questionnaire.	On Day 1 of Cycle 1, 2, 3, 4 ,5, 6, 8, 10, 12 and after that every 3 cycles, and End of treatment, assessed up to 33 months. Cycle=28 days
Number of Participants With AEs and SAEs in the Extension Phase	AEs were defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s). SAEs were defined as meeting at least 1 of the following criteria: is fatal or life-threatening, Results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, is medically significant, requires inpatient hospitalization or prolongation of existing hospitalization. AEs were assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Grade 1 to 5 were used to characterize the severity of the Adverse Event. Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening and Grade 5: death related to AE. A participant with multiple severity grades for an AE is only counted under the maximum grade.	From first dose of treatment in the Extension phase up to 30 days after last dose of treatment, assessed up approximately 37.6 months
Number of Participants With Clinical Benefit (Extension Phase)	Clinical benefit as assessed by the Investigator during Extension phase	On Day 1 of every 3 cycles, starting from Cycle 1 of the Extension phase until end of treatment, assessed up to 37.4 months. Cycle= 28 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Canadian Sub-study: Proteomic Analysis of Ribociclib and Letrozole Cohort Not Achieving Clinical Benefit Compared to a Cohort Sensitive to Treatment With Ribociclib and Letrozole	Exploratory analysis performed in archival tumor samples collected during screening in the main study. Protein expression levels of the ribociclib plus letrozole cohort that did not achieve clinical benefit (progression within 3 months of treatment) and the cohort sensitive to ribociclib and letrozole (cohort with a time to progression of 22 months or more) were determined using using Single-Pot, Solid-Phase-enhanced, Sample Preparation-Clinical Tissue Proteomics (SP3-CTP). For normalization purposes a pooled internal standard sample, comprised of aliquots of every sample included in the study, was included in each experimental batch. Protein abundances were calculated as the log2 transformed abundances relative to the pooled internal standard. Positive values represent higher protein expression levels compared to the pooled internal standard. Expression levels of proteins that showed association to predicting response to study treatment are presented.	Screening (up to 28 days before first dose of study treatment)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Caputo R, Fabi A, Romagnoli E, Baldini E, Grasso D, Fenderico N, Michelotti A. Ribociclib Plus Letrozole in Italian Male Patients with Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Case Studies of Phase 3b CompLEEment-1 Trial. Breast Cancer (Dove Med Press). 2022 Oct 18;14:351-362. doi: 10.2147/BCTT.S376902. eCollection 2022.
• Campone M, De Laurentiis M, Zamagni C, Kudryavcev I, Agterof M, Brown-Glaberman U, Palacova M, Chatterjee S, Menon-Singh L, Wu J, Martin M. Ribociclib plus letrozole in male patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: subgroup analysis of the phase IIIb CompLEEment-1 trial. Breast Cancer Res Treat. 2022 May;193(1):95-103. doi: 10.1007/s10549-022-06543-1. Epub 2022 Feb 25.
• Salvador Bofill J, Moreno Anton F, Rodriguez Sanchez CA, Galve Calvo E, Hernando Melia C, Ciruelos Gil EM, Vidal M, Jimenez-Rodriguez B, De la Cruz Merino L, Martinez Janez N, Villanueva Vazquez R, de Toro Salas R, Anton Torres A, Alvarez Lopez IM, Gavila Gregori J, Quiroga Garcia V, Vicente Rubio E, De la Haba-Rodriguez J, Gonzalez-Santiago S, Diaz Fernandez N, Barnadas Molins A, Cantos Sanchez de Ibarguen B, Delgado Mingorance JI, Bellet Ezquerra M, de Casa S, Gimeno A, Martin M. Safety and efficacy of ribociclib plus letrozole in patients with HR+, HER2- advanced breast cancer: Results from the Spanish sub-population of the phase 3b CompLEEment-1 trial. Breast. 2022 Dec;66:77-84. doi: 10.1016/j.breast.2022.09.006. Epub 2022 Sep 28.
• De Laurentiis M, Caputo R, Mazza M, Mansutti M, Masetti R, Ballatore Z, Torrisi R, Michelotti A, Zambelli A, Ferro A, Generali D, Vici P, Coltelli L, Fabi A, Marchetti P, Ballestrero A, Spazzapan S, Frassoldati A, Sarobba MG, Grasso D, Zamagni C. Safety and Efficacy of Ribociclib in Combination with Letrozole in Patients with HR+, HER2- Advanced Breast Cancer: Results from the Italian Subpopulation of Phase 3b CompLEEment-1 Study. Target Oncol. 2022 Nov;17(6):615-625. doi: 10.1007/s11523-022-00913-x. Epub 2022 Sep 24.
• De Laurentiis M, Borstnar S, Campone M, Warner E, Bofill JS, Jacot W, Dent S, Martin M, Ring A, Cottu P, Lu J, Ciruelos E, Azim HA, Chatterjee S, Zhou K, Wu J, Menon-Singh L, Zamagni C. Full population results from the core phase of CompLEEment-1, a phase 3b study of ribociclib plus letrozole as first-line therapy for advanced breast cancer in an expanded population. Breast Cancer Res Treat. 2021 Oct;189(3):689-699. doi: 10.1007/s10549-021-06334-0. Epub 2021 Aug 19. Erratum In: Breast Cancer Res Treat. 2021 Oct 8;:

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2016
• Primary Completion (Actual): November 8, 2019
• Study Completion (Actual): November 9, 2022

Study Registration Dates

• First Submitted: October 20, 2016
• First Submitted That Met QC Criteria: October 20, 2016
• First Posted (Estimated): October 21, 2016

Study Record Updates

• Last Update Posted (Actual): October 24, 2023
• Last Update Submitted That Met QC Criteria: October 23, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: LEE011; ribociclib; postmenopausal; premenopausal; advanced breast cancer; letrozole; CDK4/6; CDK4; CDK6; CDK; goserelin; HR-positive HER2-negative; Phase IIIb; ER-positive; PR-positive; men with advanced breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Letrozole; Leuprolide; Goserelin
• Other Study ID Numbers: CLEE011A2404; 2016-003467-19 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

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 https://www.clinicalstudydatarequest.com/.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes