- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01345019
Denosumab Compared to Zoledronic Acid in the Treatment of Bone Disease in Patients With Multiple Myeloma
A Randomized, Double-Blind, Multicenter Study of Denosumab Compared With Zoledronic Acid in the Treatment of Bone Disease in Subjects With Newly Diagnosed Multiple Myeloma
Study Overview
Status
Conditions
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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New South Wales
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Liverpool, New South Wales, Australia, 2170
- Research Site
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Tweed Heads, New South Wales, Australia, 2485
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Queensland
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Douglas, Queensland, Australia, 4814
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South Brisbane, Queensland, Australia, 4101
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Tasmania
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Hobart, Tasmania, Australia, 7000
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Victoria
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Clayton, Victoria, Australia, 3168
- Research Site
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Epping, Victoria, Australia, 3076
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Malvern, Victoria, Australia, 3144
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Parkville, Victoria, Australia, 3050
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Prahran, Victoria, Australia, 3181
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Graz, Austria, 8036
- Research Site
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Innsbruck, Austria, 6020
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Krems an der Donau, Austria, 3500
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Salzburg, Austria, 5020
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Wels, Austria, 4600
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Wien, Austria, 1090
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Wien, Austria, 1140
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Pleven, Bulgaria, 5800
- Research Site
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Plovdiv, Bulgaria, 4002
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Sofia, Bulgaria, 1431
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Sofia, Bulgaria, 1407
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Sofia, Bulgaria, 1756
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Sofia, Bulgaria, 1606
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Varna, Bulgaria, 9010
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Quebec, Canada, G1R 2J6
- Research Site
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British Columbia
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Burnaby, British Columbia, Canada, V5G 2X6
- Research Site
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Manitoba
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Winnipeg, Manitoba, Canada, R3E 0V9
- Research Site
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New Brunswick
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Moncton, New Brunswick, Canada, E1C 6Z8
- Research Site
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Newfoundland and Labrador
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St. Johns, Newfoundland and Labrador, Canada, A1B 3V6
- Research Site
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Ontario
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Barrie, Ontario, Canada, L4M 6M2
- Research Site
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Newmarket, Ontario, Canada, L3Y 2P9
- Research Site
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Sault Ste. Marie, Ontario, Canada, P6B 0A8
- Research Site
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Toronto, Ontario, Canada, M5B 1W8
- Research Site
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Toronto, Ontario, Canada, M2K 1E1
- Research Site
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Toronto, Ontario, Canada, M3M 0B2
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Toronto, Ontario, Canada, M6R 1B5
- Research Site
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Windsor, Ontario, Canada, N8W 2X3
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Quebec
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Laval, Quebec, Canada, H7M 3L9
- Research Site
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Montreal, Quebec, Canada, H4J 1C5
- Research Site
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Montréal, Quebec, Canada, H1T 2M4
- Research Site
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Trois-Rivières, Quebec, Canada, G8Z 3R9
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Brno, Czechia, 625 00
- Research Site
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Ostrava-Poruba, Czechia, 708 52
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Plzen, Czechia, 304 60
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Praha 10, Czechia, 100 34
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Praha 2, Czechia, 128 08
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Amiens Cedex 1, France, 80054
- Research Site
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Avignon Cedex 9, France, 84902
- Research Site
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Creteil, France, 94010
- Research Site
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Le Kremlin Bicetre, France, 94270
- Research Site
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Le Mans, France, 72000
- Research Site
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Le Mans Cedex 9, France, 72037
- Research Site
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Lille, France, 59037
- Research Site
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Lyon Cédex 3, France, 69437
- Research Site
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Marseille Cedex 9, France, 13273
- Research Site
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Marseille cedex 5, France, 13385
- Research Site
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Nantes Cedex 1, France, 44035
- Research Site
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Nice Cedex 3, France, 06202
- Research Site
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Paris, France, 75010
- Research Site
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Paris, France, 75015
- Research Site
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Paris, France, 75013
- Research Site
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Paris Cedex 12, France, 75571
- Research Site
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Paris Cedex 14, France, 75679
- Research Site
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Pessac Cedex, France, 33604
- Research Site
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Pierre-Benite cedex, France, 69495
- Research Site
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Pontoise Cedex, France, 95301
- Research Site
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Reims Cedex, France, 51056
- Research Site
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Rouen cedex, France, 76038
- Research Site
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Saint Quentin, France, 02321
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Strasbourg, France, 67000
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Villefranche Sur Saone Cedex, France, 69400
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Bonn, Germany, 53127
- Research Site
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Chemnitz, Germany, 09113
- Research Site
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Essen, Germany, 45239
- Research Site
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Hamburg, Germany, 20246
- Research Site
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Kassel, Germany, 34125
- Research Site
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Köln, Germany, 50924
- Research Site
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Leipzig, Germany, 04103
- Research Site
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Münster, Germany, 48149
- Research Site
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Regensburg, Germany, 93049
- Research Site
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Athens, Greece, 11527
- Research Site
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Athens, Greece, 11528
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Athens, Greece, 11525
- Research Site
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Heraklion, Greece, 71110
- Research Site
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Patra, Greece, 26500
- Research Site
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Piraeus, Greece, 18537
- Research Site
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Thessaloniki, Greece, 57010
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Hong Kong, Hong Kong
- Research Site
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New Territories, Hong Kong
- Research Site
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Budapest, Hungary, 1083
- Research Site
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Budapest, Hungary, 1097
- Research Site
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Debrecen, Hungary, 4032
- Research Site
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Gyor, Hungary, 9024
- Research Site
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Gyula, Hungary, 5700
- Research Site
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Kaposvar, Hungary, 7400
- Research Site
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Szeged, Hungary, 6725
- Research Site
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Dublin, Ireland, 8
- Research Site
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Dublin, Ireland, 24
- Research Site
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Dublin, Ireland, 7
- Research Site
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Limerick, Ireland
- Research Site
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Tullamore, Ireland
- Research Site
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Ancona, Italy, 60126
- Research Site
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Bari, Italy, 70124
- Research Site
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Brescia, Italy, 25125
- Research Site
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Busto Arsizio, Italy, 21052
- Research Site
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Catania, Italy, 95124
- Research Site
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Firenze, Italy, 50134
- Research Site
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Genova, Italy, 16132
- Research Site
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Messina, Italy, 98125
- Research Site
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Milano, Italy, 20153
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Napoli, Italy, 80131
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Napoli, Italy, 80136
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Novara, Italy, 28100
- Research Site
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Palermo, Italy, 90146
- Research Site
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Pescara, Italy, 65124
- Research Site
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Pisa, Italy, 56127
- Research Site
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Roma, Italy, 00144
- Research Site
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Roma, Italy, 00161
- Research Site
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Rozzano MI, Italy, 20089
- Research Site
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Torino, Italy, 10126
- Research Site
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Udine, Italy, 33100
- Research Site
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Vimercate MB, Italy, 20871
- Research Site
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Aichi
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Nagoya-shi, Aichi, Japan, 457-8510
- Research Site
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Akita
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Akita-shi, Akita, Japan, 010-8543
- Research Site
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Chiba
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Kamogawa-shi, Chiba, Japan, 296-8602
- Research Site
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Fukuoka
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Fukuoka-shi, Fukuoka, Japan, 814-0180
- Research Site
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Gifu
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Gifu-shi, Gifu, Japan, 501-1194
- Research Site
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Ogaki-shi, Gifu, Japan, 503-8502
- Research Site
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Gunma
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Maebashi-shi, Gunma, Japan, 371-8511
- Research Site
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Shibukawa-shi, Gunma, Japan, 377-8511
- Research Site
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Hiroshima
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Fukuyama-shi, Hiroshima, Japan, 720-0001
- Research Site
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Hyogo
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Kobe-shi, Hyogo, Japan, 650-0047
- Research Site
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Kumamoto
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Kumamoto-shi, Kumamoto, Japan, 860-0008
- Research Site
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Kyoto
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Kyoto-shi, Kyoto, Japan, 603-8151
- Research Site
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Okayama
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Okayama-shi, Okayama, Japan, 701-1192
- Research Site
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Saitama
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Kawagoe-shi, Saitama, Japan, 350-8550
- Research Site
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Tokushima
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Tokushima-shi, Tokushima, Japan, 770-8503
- Research Site
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Tokyo
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Shibuya-ku, Tokyo, Japan, 150-8935
- Research Site
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Shinjuku-ku, Tokyo, Japan, 162-8655
- Research Site
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Toyama
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Toyama-shi, Toyama, Japan, 930-8550
- Research Site
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Anyang, Korea, Republic of, 431-070
- Research Site
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Busan, Korea, Republic of, 602-739
- Research Site
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Daegu, Korea, Republic of, 700-721
- Research Site
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Daejeon, Korea, Republic of, 301-721
- Research Site
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Gwangju, Korea, Republic of, 519-763
- Research Site
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Incheon, Korea, Republic of, 405-760
- Research Site
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Seoul, Korea, Republic of, 135-710
- Research Site
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Seoul, Korea, Republic of, 158-710
- Research Site
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Seoul, Korea, Republic of, 120-752
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Seoul, Korea, Republic of, 137-701
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Seoul, Korea, Republic of, 110-744
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Kaunas, Lithuania, 50009
- Research Site
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Vilnius, Lithuania, LT-08661
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Ampang, Malaysia, 68000
- Research Site
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Perak
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Ipoh, Perak, Malaysia, 30990
- Research Site
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Pinang
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Georgetown, Pinang, Malaysia, 10990
- Research Site
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Sarawak
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Kuching, Sarawak, Malaysia, 93586
- Research Site
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Christchurch, New Zealand, 8011
- Research Site
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Grafton, Auckland, New Zealand, 1023
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Legnica, Poland, 59-220
- Research Site
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Lublin, Poland, 20-081
- Research Site
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Slupsk, Poland, 76-200
- Research Site
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Torun, Poland, 87-100
- Research Site
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Warszawa, Poland, 02-097
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Warszawa, Poland, 02-776
- Research Site
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Wroclaw, Poland, 53-439
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Braga, Portugal, 4710-243
- Research Site
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Coimbra, Portugal, 3000-075
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Lisboa, Portugal, 1169-050
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Matosinhos, Portugal, 4464-513
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Porto, Portugal, 4200-072
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Dzerzhinsk, Russian Federation, 606019
- Research Site
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Ekaterinburg, Russian Federation, 620102
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Moscow, Russian Federation, 115478
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Nizhny Novgorod, Russian Federation, 603126
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Novosibirsk, Russian Federation, 630051
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Penza, Russian Federation, 440071
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Petrozavodsk, Russian Federation, 185019
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Saint Petersburg, Russian Federation, 198205
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Saint-Petersburg, Russian Federation, 197110
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Saint-Petersburg, Russian Federation, 193312
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Samara, Russian Federation, 443099
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Saratov, Russian Federation, 410012
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St. Petersburg, Russian Federation, 197022
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Volgograd, Russian Federation, 400138
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Singapore, Singapore, 119228
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Singapore, Singapore, 308433
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Singapore, Singapore, 169856
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Bratislava, Slovakia, 851 07
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Nitra, Slovakia, 950 01
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Nove Zamky, Slovakia, 940 34
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Madrid, Spain, 28034
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Madrid, Spain, 28006
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Andalucía
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Sevilla, Andalucía, Spain, 41013
- Research Site
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Baleares
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Palma de Mallorca, Baleares, Spain, 07198
- Research Site
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Castilla León
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Salamanca, Castilla León, Spain, 37007
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Cataluña
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Badalona, Cataluña, Spain, 08916
- Research Site
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Barcelona, Cataluña, Spain, 08036
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Comunidad Valenciana
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Valencia, Comunidad Valenciana, Spain, 46017
- Research Site
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Valencia, Comunidad Valenciana, Spain, 46026
- Research Site
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Galicia
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Ourense, Galicia, Spain, 32005
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País Vasco
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San Sebastian, País Vasco, Spain, 20014
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Chur, Switzerland, 7000
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Zurich, Switzerland, 8032
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Zurich, Switzerland, 8038
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Changhua, Taiwan, 50006
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Kaohsiung, Taiwan, 83301
- Research Site
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Taichung, Taiwan, 40447
- Research Site
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Taichung, Taiwan, 407
- Research Site
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Tainan, Taiwan, 70403
- Research Site
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Taipei, Taiwan, 10002
- Research Site
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Taoyuan, Taiwan, 33305
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Adana, Turkey, 01330
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Ankara, Turkey, 06100
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Ankara, Turkey, 06500
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Istanbul, Turkey, 34452
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Izmir, Turkey, 35340
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Cherkasy, Ukraine, 18009
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Dnipropetrovsk, Ukraine, 49102
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Ivano-Frankivsk, Ukraine, 76008
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Khmelnitskiy, Ukraine, 29000
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Kyiv, Ukraine, 04107
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Lviv, Ukraine, 79031
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Poltava, Ukraine, 36024
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Harrow, United Kingdom, HA1 3UJ
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Inverness, United Kingdom, IV2 3UJ
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Leeds, United Kingdom, LS9 7TF
- Research Site
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London, United Kingdom, NW3 2QG
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London, United Kingdom, SW17 0RE
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Oxford, United Kingdom, OX3 7LJ
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Arizona
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Tucson, Arizona, United States, 85704
- Research Site
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Arkansas
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Fayetteville, Arkansas, United States, 72703
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California
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Anaheim, California, United States, 92801
- Research Site
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Campbell, California, United States, 95008
- Research Site
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Encinitas, California, United States, 92024
- Research Site
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Fresno, California, United States, 93720
- Research Site
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Pleasant Hill, California, United States, 94523
- Research Site
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Santa Barbara, California, United States, 93105
- Research Site
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Santa Maria, California, United States, 93454
- Research Site
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Connecticut
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Stamford, Connecticut, United States, 06902
- Research Site
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District of Columbia
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Washington, District of Columbia, United States, 20007
- Research Site
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Washington, District of Columbia, United States, 20010
- Research Site
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Florida
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Boynton Beach, Florida, United States, 33426
- Research Site
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Boynton Beach, Florida, United States, 33435
- Research Site
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Jacksonville, Florida, United States, 32256
- Research Site
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Georgia
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Columbus, Georgia, United States, 31904
- Research Site
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Savannah, Georgia, United States, 31405
- Research Site
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Illinois
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Chicago, Illinois, United States, 60612
- Research Site
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Joliet, Illinois, United States, 60435
- Research Site
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Maywood, Illinois, United States, 60153
- Research Site
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Niles, Illinois, United States, 60714
- Research Site
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Skokie, Illinois, United States, 60076
- Research Site
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Skokie, Illinois, United States, 60077
- Research Site
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Indiana
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Anderson, Indiana, United States, 46016
- Research Site
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Fort Wayne, Indiana, United States, 46845
- Research Site
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Indianapolis, Indiana, United States, 46202
- Research Site
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Iowa
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Ames, Iowa, United States, 50010
- Research Site
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Iowa City, Iowa, United States, 52242
- Research Site
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Kentucky
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Paducah, Kentucky, United States, 42003
- Research Site
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Louisiana
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New Orleans, Louisiana, United States, 70121
- Research Site
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Maine
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Scarborough, Maine, United States, 04074
- Research Site
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Maryland
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Baltimore, Maryland, United States, 21204
- Research Site
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Baltimore, Maryland, United States, 21237
- Research Site
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Baltimore, Maryland, United States, 21229
- Research Site
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Bethesda, Maryland, United States, 20817
- Research Site
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Westminster, Maryland, United States, 21157
- Research Site
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Massachusetts
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Boston, Massachusetts, United States, 02114
- Research Site
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Boston, Massachusetts, United States, 02215
- Research Site
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Danvers, Massachusetts, United States, 01923
- Research Site
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Fairhaven, Massachusetts, United States, 02719
- Research Site
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Michigan
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Detroit, Michigan, United States, 48201
- Research Site
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Lansing, Michigan, United States, 48910
- Research Site
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Mississippi
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Jackson, Mississippi, United States, 39216
- Research Site
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Missouri
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Springfield, Missouri, United States, 65806
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Montana
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Billings, Montana, United States, 59101
- Research Site
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Nebraska
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Lincoln, Nebraska, United States, 68506
- Research Site
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Omaha, Nebraska, United States, 68198
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Nevada
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North Las Vegas, Nevada, United States, 89086
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New Jersey
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Hackensack, New Jersey, United States, 07601
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New York
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Lake Success, New York, United States, 11042
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New York, New York, United States, 10021
- Research Site
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Rochester, New York, United States, 14621
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North Carolina
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Fayetteville, North Carolina, United States, 28304
- Research Site
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Goldsboro, North Carolina, United States, 27534
- Research Site
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High Point, North Carolina, United States, 27262
- Research Site
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North Dakota
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Bismarck, North Dakota, United States, 58501
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Oklahoma
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Oklahoma City, Oklahoma, United States, 73120-8345
- Research Site
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Pennsylvania
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Hershey, Pennsylvania, United States, 17033
- Research Site
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Philadelphia, Pennsylvania, United States, 19106
- Research Site
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Philadelphia, Pennsylvania, United States, 19140
- Research Site
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Philadelphia, Pennsylvania, United States, 19141
- Research Site
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West Reading, Pennsylvania, United States, 19611
- Research Site
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South Carolina
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Charleston, South Carolina, United States, 29406
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Charleston, South Carolina, United States, 29414
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Greenville, South Carolina, United States, 29615
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South Dakota
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Aberdeen, South Dakota, United States, 57401
- Research Site
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Rapid City, South Dakota, United States, 57701
- Research Site
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Sioux Falls, South Dakota, United States, 57105
- Research Site
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Watertown, South Dakota, United States, 57201
- Research Site
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Tennessee
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Memphis, Tennessee, United States, 38120
- Research Site
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Texas
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Houston, Texas, United States, 77030
- Research Site
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Lubbock, Texas, United States, 79415
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Utah
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Salt Lake City, Utah, United States, 84106
- Research Site
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Virginia
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Christiansburg, Virginia, United States, 24073
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Washington
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Spokane, Washington, United States, 99208
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Tacoma, Washington, United States, 98405
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West Virginia
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Morgantown, West Virginia, United States, 26506
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Wisconsin
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Minocqua, Wisconsin, United States, 54548
- Research Site
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Wauwatosa, Wisconsin, United States, 53226
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Documented evidence of multiple myeloma (per local assessment):
- Monoclonal plasma cells in the bone marrow greater than or equal to 10% and/or presence of a biopsy-proven plasmacytoma, and
- Monoclonal protein present in the serum and/or urine
- Radiographic (X-ray, or computer tomography [CT]) evidence of at least 1 lytic bone lesion (or at least 1 focal lesion per magnetic resonance imaging [MRI])
- Plan to receive or is receiving primary frontline anti-myeloma therapies
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- Age ≥ 18 years
Adequate organ function, as defined by the following criteria (per central or local laboratory values):
- Serum aspartate aminotransferase (AST) ≤ 2.0 x upper limit of normal (ULN)
- Serum alanine aminotransferase ≤ (ALT) 2.0 x ULN
- Serum total bilirubin ≤ 2.0 x ULN
- Creatinine clearance ≥ 30 mL/min
- Serum calcium or albumin-adjusted serum calcium 2.0 mmol/L (8.0 mg/dL) and 2.9 mmol/L (11.5 mg/dL)
- Written informed consent before any study-specific procedure is performed
Exclusion Criteria:
- Nonsecretory multiple myeloma based upon standard M-component criteria (ie, measurable serum/urine M-component) unless the baseline serum free light chain level is elevated
- POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- Plasma cell leukemia
- More than 30 days of previous treatment (before screening) with anti-myeloma therapy (does not include radiotherapy or a single short course of steroid [ie, less than or equal to the equivalent of dexamethasone 60 mg/day for 4 days]).
- Planned radiation therapy or surgery to the bone (does not include procedures performed before randomization)
- Prior administration of denosumab
- Use of oral bisphosphonates with a cumulative exposure of more than 1 year
- More than 1 previous dose of IV bisphosphonate administration
- Prior history or current evidence of osteonecrosis/osteomyelitis of the jaw
- Active dental or jaw condition which requires oral surgery, including tooth extraction
- Non-healed dental/oral surgery, including tooth extraction
- Planned invasive dental procedures
Evidence of any of the following conditions per subject self-report or medical chart review:
- Any prior invasive malignancy within 5 years before randomization
- Any non-invasive malignancy not treated with curative intent or with knownactive disease within 5 years before randomization
- Major surgery or significant traumatic injury occurring within 4 weeks before randomization
- Active infection with Hepatitis B virus or Hepatitis C virus
- Known infection with human immunodeficiency virus (HIV)
- Active infection requiring IV anti-infective therapy
- Subject is pregnant or breast feeding, or planning to become pregnant within 5 months after end of treatment
- Female subject of child bearing potential is not willing to use highly effective contraception during treatment and for 5 months after the end of treatment (see section 6.3)
- Known sensitivity to any of the products to be administered during the study (eg, mammalian derived products, calcium or vitamin D)
- Subject is receiving or is less than 30 days since ending other experimental device or drug (no marketing authorization for any indication)
- Subject will not be available for follow-up assessment
- Any major medical or psychiatric disorder that in the opinion of the investigator, might prevent the subject from completing the study or interfere with the interpretation of the study results
Study Plan
How is the study designed?
Design Details
- Primary Purpose: SUPPORTIVE_CARE
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
ACTIVE_COMPARATOR: Zoledronic acid
Zoledronic acid 4 mg intravenously plus placebo to denosumab subcutaniously (SC) once every 4 weeks (Q4W) in the double-blind treatment period (Since denosumab was determined to have a positive benefit:risk profile in the primary analysis of the study, per protocol, participants who were still undergoing Q4W scheduled assessments were offered open-label denosumab 120 mg SC Q4W for up to 2 years)
|
Administered by intravenous infusion over 15 minutes once every 4 weeks
Other Names:
Administered by subcutaneous injection once every 4 weeks.
Administered by subcutaneous injection once every 4 weeks.
Other Names:
|
EXPERIMENTAL: Denosumab
Denosumab 120 mg subcutaniously (SC) plus placebo to zoledronic acid intravenously once every 4 weeks (Q4W) in the double-blind treatment period (Since denosumab was determined to have a positive benefit:risk profile in the primary analysis of the study, per protocol, participants who were still undergoing Q4W scheduled assessments were offered open-label denosumab 120 mg SC Q4W for up to 2 years)
|
Administered by subcutaneous injection once every 4 weeks.
Other Names:
Administered by subcutaneous injection once every 4 weeks.
Other Names:
Administered by intravenous infusion over 15 minutes once every 4 weeks
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to First On-study Skeletal Related Event
Time Frame: From randomization until the primary analysis data cut-off date of 19 July 2016 (per protocol); median time on study was 17.6 and 17.3 months in each treatment group respectively.
|
A skeletal-related event (SRE) is defined as one of the following: pathologic fracture (vertebral or non-vertebral), radiation therapy to bone (including the use of radioisotopes), surgery to bone, or spinal cord compression.
Time to first on-study SRE is defined as the time interval (in days) from the randomization date to the date of first occurrence of on-study SRE.
If there was no known event, and the participant was monitored for any one of the four SRE components, time to first on-study SRE was censored at the end of the treatment phase date or the primary analysis data cut-off date, whichever came first.
|
From randomization until the primary analysis data cut-off date of 19 July 2016 (per protocol); median time on study was 17.6 and 17.3 months in each treatment group respectively.
|
Percentage of Participants With an On-study Skeletal Related Event
Time Frame: From randomization until the primary analysis data cut-off date of 19 July 2016 (per protocol); median time on study was 17.6 and 17.3 months in each treatment group respectively.
|
A skeletal-related event (SRE) is defined as one of the following: pathologic fracture (vertebral or non-vertebral), radiation therapy to bone (including the use of radioisotopes), surgery to bone, or spinal cord compression.
|
From randomization until the primary analysis data cut-off date of 19 July 2016 (per protocol); median time on study was 17.6 and 17.3 months in each treatment group respectively.
|
Kaplan-Meier Estimate of Percentage of Participants With an On-study Skeletal Related Event
Time Frame: From randomization until the primary analysis data cut-off date of 19 July 2016 (per protocol); median time on study was 17.6 and 17.3 months in each treatment group respectively. The Kaplan-Meier estimate at weeks 25, 49 and 109 is reported.
|
A skeletal-related event (SRE) is defined as one of the following: pathologic fracture (vertebral or non-vertebral), radiation therapy to bone (including the use of radioisotopes), surgery to bone, or spinal cord compression.
|
From randomization until the primary analysis data cut-off date of 19 July 2016 (per protocol); median time on study was 17.6 and 17.3 months in each treatment group respectively. The Kaplan-Meier estimate at weeks 25, 49 and 109 is reported.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to First On-study Skeletal Related Event - Superiority Analysis
Time Frame: From randomization until the primary analysis data cut-off date of 19 July 2016 (per protocol); median time on study was 17.6 and 17.3 months in each treatment group respectively.
|
A skeletal-related event (SRE) is defined as one of the following: pathologic fracture (vertebral or non-vertebral), radiation therapy to bone (including the use of radioisotopes), surgery to bone, or spinal cord compression.
Time to first on-study SRE is defined as the time interval (in days) from the randomization date to the date of first occurrence of on-study SRE.
If there was no known event, and the participant was monitored for any one of the four SRE components, time to first on-study SRE was censored at the end of the treatment phase date or the primary analysis data cut-off date, whichever came first.
|
From randomization until the primary analysis data cut-off date of 19 July 2016 (per protocol); median time on study was 17.6 and 17.3 months in each treatment group respectively.
|
Time to First and Subsequent On-Study Skeletal Related Event - Number of Events Per Patient
Time Frame: From randomization until the primary analysis data cut-off date of 19 July 2016 (per protocol); median time on study was 17.6 and 17.3 months in each treatment group respectively.
|
A skeletal-related event (SRE) is defined as one of the following: pathologic fracture (vertebral or non-vertebral), radiation therapy to bone (including the use of radioisotopes), surgery to bone, or spinal cord compression. Time to first on-study SRE is defined as the time interval (in days) from the randomization date to the date of first occurrence of on-study SRE. Time to a subsequent SRE is defined, similarly to the time to first on-study SRE, as the time interval from the randomization date to the date of a subsequent occurrence of on-study SRE, which had to be at least 21 days after the previous SRE. A multiple event analysis was used, which accounts for both the absolute number of SREs and for the time between two consecutive events, and therefore, provides a more sensitive assessment of the risk of experiencing an SRE. The average number of events per patient is reported. |
From randomization until the primary analysis data cut-off date of 19 July 2016 (per protocol); median time on study was 17.6 and 17.3 months in each treatment group respectively.
|
Time to First and Subsequent On-Study Skeletal Related Event - Number of Events
Time Frame: From randomization until the primary analysis data cut-off date of 19 July 2016 (per protocol); median time on study was 17.6 and 17.3 months in each treatment group respectively.
|
A skeletal-related event (SRE) is defined as one of the following: pathologic fracture (vertebral or non-vertebral), radiation therapy to bone (including the use of radioisotopes), surgery to bone, or spinal cord compression. Time to first on-study SRE is defined as the time interval (in days) from the randomization date to the date of first occurrence of on-study SRE. Time to a subsequent SRE is defined, similarly to the time to first on-study SRE, as the time interval from the randomization date to the date of a subsequent occurrence of on-study SRE, which had to be at least 21 days after the previous SRE. A multiple event analysis was used, which accounts for both the absolute number of SREs and for the time between two consecutive events, and therefore, provides a more sensitive assessment of the risk of experiencing an SRE. The total number of events is reported. |
From randomization until the primary analysis data cut-off date of 19 July 2016 (per protocol); median time on study was 17.6 and 17.3 months in each treatment group respectively.
|
Overall Survival
Time Frame: From randomization until the primary analysis data cut-off date of 19 July 2016 (per protocol); median time on study was 17.6 and 17.3 months in each treatment group respectively.
|
Overall survival was defined as the time interval (in days) from the randomization date to the date of death.
If a participant was still alive at the primary analysis data cut-off date or was lost to follow-up by the primary analysis data cut-off date, survival time was censored at their last contact date or the primary analysis data cut-off date, whichever was first.
|
From randomization until the primary analysis data cut-off date of 19 July 2016 (per protocol); median time on study was 17.6 and 17.3 months in each treatment group respectively.
|
Percentage of Participants Who Died
Time Frame: From randomization until the primary analysis data cut-off date of 19 July 2016 (per protocol); median time on study was 17.6 and 17.3 months in each treatment group respectively.
|
From randomization until the primary analysis data cut-off date of 19 July 2016 (per protocol); median time on study was 17.6 and 17.3 months in each treatment group respectively.
|
Collaborators and Investigators
Sponsor
Collaborators
Publications and helpful links
General Publications
- Raje N, Roodman GD, Willenbacher W, Shimizu K, Garcia-Sanz R, Terpos E, Kennedy L, Sabatelli L, Intorcia M, Hechmati G. A cost-effectiveness analysis of denosumab for the prevention of skeletal-related events in patients with multiple myeloma in the United States of America. J Med Econ. 2018 May;21(5):525-536. doi: 10.1080/13696998.2018.1445634. Epub 2018 Mar 5.
- Raje N, Terpos E, Willenbacher W, Shimizu K, Garcia-Sanz R, Durie B, Legiec W, Krejci M, Laribi K, Zhu L, Cheng P, Warner D, Roodman GD. Denosumab versus zoledronic acid in bone disease treatment of newly diagnosed multiple myeloma: an international, double-blind, double-dummy, randomised, controlled, phase 3 study. Lancet Oncol. 2018 Mar;19(3):370-381. doi: 10.1016/S1470-2045(18)30072-X. Epub 2018 Feb 9.
- Huang SY, Yoon SS, Shimizu K, Chng WJ, Chang CS, Wong RS, Gao S, Wang Y, Gordon SW, Glennane A, Min CK. Denosumab Versus Zoledronic Acid in Bone Disease Treatment of Newly Diagnosed Multiple Myeloma: An International, Double-Blind, Randomized Controlled Phase 3 Study-Asian Subgroup Analysis. Adv Ther. 2020 Jul;37(7):3404-3416. doi: 10.1007/s12325-020-01395-x. Epub 2020 Jun 10.
- Terpos E, Raje N, Croucher P, Garcia-Sanz R, Leleu X, Pasteiner W, Wang Y, Glennane A, Canon J, Pawlyn C. Denosumab compared with zoledronic acid on PFS in multiple myeloma: exploratory results of an international phase 3 study. Blood Adv. 2021 Feb 9;5(3):725-736. doi: 10.1182/bloodadvances.2020002378.
Helpful Links
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
- Neoplasms
- bone metastases
- Hematologic Diseases
- fractures
- Bone Diseases
- Bone Marrow Diseases
- bisphosphonates
- hematologic malignancies
- multiple myeloma
- Bone Density Conservation Agents
- zoledronic acid
- Neoplasms, Plasma Cell
- Paraproteinemias
- Blood Protein Disorders
- blood cancer
- spinal cord compression
- myeloma
- Neoplasm Metastasis
- denosumab
- Neoplastic Processes
- lytic bone lesions
- Bone Neoplasms
- SRE
- skeletal-related event
- radiation to bone
- surgery to bone
- Diphosphonates
Additional Relevant MeSH Terms
- Pathologic Processes
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Neoplasms by Site
- Hematologic Diseases
- Hemorrhagic Disorders
- Musculoskeletal Diseases
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Neoplastic Processes
- Neoplasms
- Hematologic Neoplasms
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Neoplasm Metastasis
- Bone Diseases
- Physiological Effects of Drugs
- Bone Density Conservation Agents
- Zoledronic Acid
- Denosumab
Other Study ID Numbers
- 20090482
- 2010-020454-34 (EUDRACT_NUMBER)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
- CSR
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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