Denosumab Compared to Zoledronic Acid in the Treatment of Bone Disease in Patients With Multiple Myeloma

November 4, 2022 updated by: Amgen

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

The purpose of this study is to determine if denosumab is non-inferior to zoledronic acid in the treatment of bone disease from multiple myeloma.

Study Overview

Study Type

Interventional

Enrollment (Actual)

1718

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • New South Wales
      • Liverpool, New South Wales, Australia, 2170
        • Research Site
      • Tweed Heads, New South Wales, Australia, 2485
        • Research Site
    • Queensland
      • Douglas, Queensland, Australia, 4814
        • Research Site
      • South Brisbane, Queensland, Australia, 4101
        • Research Site
    • Tasmania
      • Hobart, Tasmania, Australia, 7000
        • Research Site
    • Victoria
      • Clayton, Victoria, Australia, 3168
        • Research Site
      • Epping, Victoria, Australia, 3076
        • Research Site
      • Malvern, Victoria, Australia, 3144
        • Research Site
      • Parkville, Victoria, Australia, 3050
        • Research Site
      • Prahran, Victoria, Australia, 3181
        • Research Site
      • Graz, Austria, 8036
        • Research Site
      • Innsbruck, Austria, 6020
        • Research Site
      • Krems an der Donau, Austria, 3500
        • Research Site
      • Salzburg, Austria, 5020
        • Research Site
      • Wels, Austria, 4600
        • Research Site
      • Wien, Austria, 1090
        • Research Site
      • Wien, Austria, 1140
        • Research Site
      • Pleven, Bulgaria, 5800
        • Research Site
      • Plovdiv, Bulgaria, 4002
        • Research Site
      • Sofia, Bulgaria, 1431
        • Research Site
      • Sofia, Bulgaria, 1407
        • Research Site
      • Sofia, Bulgaria, 1756
        • Research Site
      • Sofia, Bulgaria, 1606
        • Research Site
      • Varna, Bulgaria, 9010
        • Research Site
      • Quebec, Canada, G1R 2J6
        • Research Site
    • British Columbia
      • Burnaby, British Columbia, Canada, V5G 2X6
        • Research Site
    • Manitoba
      • Winnipeg, Manitoba, Canada, R3E 0V9
        • Research Site
    • New Brunswick
      • Moncton, New Brunswick, Canada, E1C 6Z8
        • Research Site
    • Newfoundland and Labrador
      • St. Johns, Newfoundland and Labrador, Canada, A1B 3V6
        • Research Site
    • Ontario
      • Barrie, Ontario, Canada, L4M 6M2
        • Research Site
      • Newmarket, Ontario, Canada, L3Y 2P9
        • Research Site
      • Sault Ste. Marie, Ontario, Canada, P6B 0A8
        • Research Site
      • Toronto, Ontario, Canada, M5B 1W8
        • Research Site
      • Toronto, Ontario, Canada, M2K 1E1
        • Research Site
      • Toronto, Ontario, Canada, M3M 0B2
        • Research Site
      • Toronto, Ontario, Canada, M6R 1B5
        • Research Site
      • Windsor, Ontario, Canada, N8W 2X3
        • Research Site
    • Quebec
      • Laval, Quebec, Canada, H7M 3L9
        • Research Site
      • Montreal, Quebec, Canada, H4J 1C5
        • Research Site
      • Montréal, Quebec, Canada, H1T 2M4
        • Research Site
      • Trois-Rivières, Quebec, Canada, G8Z 3R9
        • Research Site
      • Brno, Czechia, 625 00
        • Research Site
      • Ostrava-Poruba, Czechia, 708 52
        • Research Site
      • Plzen, Czechia, 304 60
        • Research Site
      • Praha 10, Czechia, 100 34
        • Research Site
      • Praha 2, Czechia, 128 08
        • Research Site
      • Amiens Cedex 1, France, 80054
        • Research Site
      • Avignon Cedex 9, France, 84902
        • Research Site
      • Creteil, France, 94010
        • Research Site
      • Le Kremlin Bicetre, France, 94270
        • Research Site
      • Le Mans, France, 72000
        • Research Site
      • Le Mans Cedex 9, France, 72037
        • Research Site
      • Lille, France, 59037
        • Research Site
      • Lyon Cédex 3, France, 69437
        • Research Site
      • Marseille Cedex 9, France, 13273
        • Research Site
      • Marseille cedex 5, France, 13385
        • Research Site
      • Nantes Cedex 1, France, 44035
        • Research Site
      • Nice Cedex 3, France, 06202
        • Research Site
      • Paris, France, 75010
        • Research Site
      • Paris, France, 75015
        • Research Site
      • Paris, France, 75013
        • Research Site
      • Paris Cedex 12, France, 75571
        • Research Site
      • Paris Cedex 14, France, 75679
        • Research Site
      • Pessac Cedex, France, 33604
        • Research Site
      • Pierre-Benite cedex, France, 69495
        • Research Site
      • Pontoise Cedex, France, 95301
        • Research Site
      • Reims Cedex, France, 51056
        • Research Site
      • Rouen cedex, France, 76038
        • Research Site
      • Saint Quentin, France, 02321
        • Research Site
      • Strasbourg, France, 67000
        • Research Site
      • Villefranche Sur Saone Cedex, France, 69400
        • Research Site
      • Bonn, Germany, 53127
        • Research Site
      • Chemnitz, Germany, 09113
        • Research Site
      • Essen, Germany, 45239
        • Research Site
      • Hamburg, Germany, 20246
        • Research Site
      • Kassel, Germany, 34125
        • Research Site
      • Köln, Germany, 50924
        • Research Site
      • Leipzig, Germany, 04103
        • Research Site
      • Münster, Germany, 48149
        • Research Site
      • Regensburg, Germany, 93049
        • Research Site
      • Athens, Greece, 11527
        • Research Site
      • Athens, Greece, 11528
        • Research Site
      • Athens, Greece, 11525
        • Research Site
      • Heraklion, Greece, 71110
        • Research Site
      • Patra, Greece, 26500
        • Research Site
      • Piraeus, Greece, 18537
        • Research Site
      • Thessaloniki, Greece, 57010
        • Research Site
      • Hong Kong, Hong Kong
        • Research Site
      • New Territories, Hong Kong
        • Research Site
      • Budapest, Hungary, 1083
        • Research Site
      • Budapest, Hungary, 1097
        • Research Site
      • Debrecen, Hungary, 4032
        • Research Site
      • Gyor, Hungary, 9024
        • Research Site
      • Gyula, Hungary, 5700
        • Research Site
      • Kaposvar, Hungary, 7400
        • Research Site
      • Szeged, Hungary, 6725
        • Research Site
      • Dublin, Ireland, 8
        • Research Site
      • Dublin, Ireland, 24
        • Research Site
      • Dublin, Ireland, 7
        • Research Site
      • Limerick, Ireland
        • Research Site
      • Tullamore, Ireland
        • Research Site
      • Ancona, Italy, 60126
        • Research Site
      • Bari, Italy, 70124
        • Research Site
      • Brescia, Italy, 25125
        • Research Site
      • Busto Arsizio, Italy, 21052
        • Research Site
      • Catania, Italy, 95124
        • Research Site
      • Firenze, Italy, 50134
        • Research Site
      • Genova, Italy, 16132
        • Research Site
      • Messina, Italy, 98125
        • Research Site
      • Milano, Italy, 20153
        • Research Site
      • Napoli, Italy, 80131
        • Research Site
      • Napoli, Italy, 80136
        • Research Site
      • Novara, Italy, 28100
        • Research Site
      • Palermo, Italy, 90146
        • Research Site
      • Pescara, Italy, 65124
        • Research Site
      • Pisa, Italy, 56127
        • Research Site
      • Roma, Italy, 00144
        • Research Site
      • Roma, Italy, 00161
        • Research Site
      • Rozzano MI, Italy, 20089
        • Research Site
      • Torino, Italy, 10126
        • Research Site
      • Udine, Italy, 33100
        • Research Site
      • Vimercate MB, Italy, 20871
        • Research Site
    • Aichi
      • Nagoya-shi, Aichi, Japan, 457-8510
        • Research Site
    • Akita
      • Akita-shi, Akita, Japan, 010-8543
        • Research Site
    • Chiba
      • Kamogawa-shi, Chiba, Japan, 296-8602
        • Research Site
    • Fukuoka
      • Fukuoka-shi, Fukuoka, Japan, 814-0180
        • Research Site
    • Gifu
      • Gifu-shi, Gifu, Japan, 501-1194
        • Research Site
      • Ogaki-shi, Gifu, Japan, 503-8502
        • Research Site
    • Gunma
      • Maebashi-shi, Gunma, Japan, 371-8511
        • Research Site
      • Shibukawa-shi, Gunma, Japan, 377-8511
        • Research Site
    • Hiroshima
      • Fukuyama-shi, Hiroshima, Japan, 720-0001
        • Research Site
    • Hyogo
      • Kobe-shi, Hyogo, Japan, 650-0047
        • Research Site
    • Kumamoto
      • Kumamoto-shi, Kumamoto, Japan, 860-0008
        • Research Site
    • Kyoto
      • Kyoto-shi, Kyoto, Japan, 603-8151
        • Research Site
    • Okayama
      • Okayama-shi, Okayama, Japan, 701-1192
        • Research Site
    • Saitama
      • Kawagoe-shi, Saitama, Japan, 350-8550
        • Research Site
    • Tokushima
      • Tokushima-shi, Tokushima, Japan, 770-8503
        • Research Site
    • Tokyo
      • Shibuya-ku, Tokyo, Japan, 150-8935
        • Research Site
      • Shinjuku-ku, Tokyo, Japan, 162-8655
        • Research Site
    • Toyama
      • Toyama-shi, Toyama, Japan, 930-8550
        • Research Site
      • Anyang, Korea, Republic of, 431-070
        • Research Site
      • Busan, Korea, Republic of, 602-739
        • Research Site
      • Daegu, Korea, Republic of, 700-721
        • Research Site
      • Daejeon, Korea, Republic of, 301-721
        • Research Site
      • Gwangju, Korea, Republic of, 519-763
        • Research Site
      • Incheon, Korea, Republic of, 405-760
        • Research Site
      • Seoul, Korea, Republic of, 135-710
        • Research Site
      • Seoul, Korea, Republic of, 158-710
        • Research Site
      • Seoul, Korea, Republic of, 120-752
        • Research Site
      • Seoul, Korea, Republic of, 137-701
        • Research Site
      • Seoul, Korea, Republic of, 110-744
        • Research Site
      • Kaunas, Lithuania, 50009
        • Research Site
      • Vilnius, Lithuania, LT-08661
        • Research Site
      • Ampang, Malaysia, 68000
        • Research Site
    • Perak
      • Ipoh, Perak, Malaysia, 30990
        • Research Site
    • Pinang
      • Georgetown, Pinang, Malaysia, 10990
        • Research Site
    • Sarawak
      • Kuching, Sarawak, Malaysia, 93586
        • Research Site
      • Christchurch, New Zealand, 8011
        • Research Site
      • Grafton, Auckland, New Zealand, 1023
        • Research Site
      • Legnica, Poland, 59-220
        • Research Site
      • Lublin, Poland, 20-081
        • Research Site
      • Slupsk, Poland, 76-200
        • Research Site
      • Torun, Poland, 87-100
        • Research Site
      • Warszawa, Poland, 02-097
        • Research Site
      • Warszawa, Poland, 02-776
        • Research Site
      • Wroclaw, Poland, 53-439
        • Research Site
      • Braga, Portugal, 4710-243
        • Research Site
      • Coimbra, Portugal, 3000-075
        • Research Site
      • Lisboa, Portugal, 1169-050
        • Research Site
      • Matosinhos, Portugal, 4464-513
        • Research Site
      • Porto, Portugal, 4200-072
        • Research Site
      • Dzerzhinsk, Russian Federation, 606019
        • Research Site
      • Ekaterinburg, Russian Federation, 620102
        • Research Site
      • Moscow, Russian Federation, 115478
        • Research Site
      • Nizhny Novgorod, Russian Federation, 603126
        • Research Site
      • Novosibirsk, Russian Federation, 630051
        • Research Site
      • Penza, Russian Federation, 440071
        • Research Site
      • Petrozavodsk, Russian Federation, 185019
        • Research Site
      • Saint Petersburg, Russian Federation, 198205
        • Research Site
      • Saint-Petersburg, Russian Federation, 197110
        • Research Site
      • Saint-Petersburg, Russian Federation, 193312
        • Research Site
      • Samara, Russian Federation, 443099
        • Research Site
      • Saratov, Russian Federation, 410012
        • Research Site
      • St. Petersburg, Russian Federation, 197022
        • Research Site
      • Volgograd, Russian Federation, 400138
        • Research Site
      • Singapore, Singapore, 119228
        • Research Site
      • Singapore, Singapore, 308433
        • Research Site
      • Singapore, Singapore, 169856
        • Research Site
      • Bratislava, Slovakia, 851 07
        • Research Site
      • Nitra, Slovakia, 950 01
        • Research Site
      • Nove Zamky, Slovakia, 940 34
        • Research Site
      • Madrid, Spain, 28034
        • Research Site
      • Madrid, Spain, 28006
        • Research Site
    • Andalucía
      • Sevilla, Andalucía, Spain, 41013
        • Research Site
    • Baleares
      • Palma de Mallorca, Baleares, Spain, 07198
        • Research Site
    • Castilla León
      • Salamanca, Castilla León, Spain, 37007
        • Research Site
    • Cataluña
      • Badalona, Cataluña, Spain, 08916
        • Research Site
      • Barcelona, Cataluña, Spain, 08036
        • Research Site
    • Comunidad Valenciana
      • Valencia, Comunidad Valenciana, Spain, 46017
        • Research Site
      • Valencia, Comunidad Valenciana, Spain, 46026
        • Research Site
    • Galicia
      • Ourense, Galicia, Spain, 32005
        • Research Site
    • País Vasco
      • San Sebastian, País Vasco, Spain, 20014
        • Research Site
      • Chur, Switzerland, 7000
        • Research Site
      • Zurich, Switzerland, 8032
        • Research Site
      • Zurich, Switzerland, 8038
        • Research Site
      • Changhua, Taiwan, 50006
        • Research Site
      • Kaohsiung, Taiwan, 83301
        • Research Site
      • Taichung, Taiwan, 40447
        • Research Site
      • Taichung, Taiwan, 407
        • Research Site
      • Tainan, Taiwan, 70403
        • Research Site
      • Taipei, Taiwan, 10002
        • Research Site
      • Taoyuan, Taiwan, 33305
        • Research Site
      • Adana, Turkey, 01330
        • Research Site
      • Ankara, Turkey, 06100
        • Research Site
      • Ankara, Turkey, 06500
        • Research Site
      • Istanbul, Turkey, 34452
        • Research Site
      • Izmir, Turkey, 35340
        • Research Site
      • Cherkasy, Ukraine, 18009
        • Research Site
      • Dnipropetrovsk, Ukraine, 49102
        • Research Site
      • Ivano-Frankivsk, Ukraine, 76008
        • Research Site
      • Khmelnitskiy, Ukraine, 29000
        • Research Site
      • Kyiv, Ukraine, 04107
        • Research Site
      • Lviv, Ukraine, 79031
        • Research Site
      • Poltava, Ukraine, 36024
        • Research Site
      • Harrow, United Kingdom, HA1 3UJ
        • Research Site
      • Inverness, United Kingdom, IV2 3UJ
        • Research Site
      • Leeds, United Kingdom, LS9 7TF
        • Research Site
      • London, United Kingdom, NW3 2QG
        • Research Site
      • London, United Kingdom, SW17 0RE
        • Research Site
      • Oxford, United Kingdom, OX3 7LJ
        • Research Site
    • Arizona
      • Tucson, Arizona, United States, 85704
        • Research Site
    • Arkansas
      • Fayetteville, Arkansas, United States, 72703
        • Research Site
    • California
      • Anaheim, California, United States, 92801
        • Research Site
      • Campbell, California, United States, 95008
        • Research Site
      • Encinitas, California, United States, 92024
        • Research Site
      • Fresno, California, United States, 93720
        • Research Site
      • Pleasant Hill, California, United States, 94523
        • Research Site
      • Santa Barbara, California, United States, 93105
        • Research Site
      • Santa Maria, California, United States, 93454
        • Research Site
    • Connecticut
      • Stamford, Connecticut, United States, 06902
        • Research Site
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Research Site
      • Washington, District of Columbia, United States, 20010
        • Research Site
    • Florida
      • Boynton Beach, Florida, United States, 33426
        • Research Site
      • Boynton Beach, Florida, United States, 33435
        • Research Site
      • Jacksonville, Florida, United States, 32256
        • Research Site
    • Georgia
      • Columbus, Georgia, United States, 31904
        • Research Site
      • Savannah, Georgia, United States, 31405
        • Research Site
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Research Site
      • Joliet, Illinois, United States, 60435
        • Research Site
      • Maywood, Illinois, United States, 60153
        • Research Site
      • Niles, Illinois, United States, 60714
        • Research Site
      • Skokie, Illinois, United States, 60076
        • Research Site
      • Skokie, Illinois, United States, 60077
        • Research Site
    • Indiana
      • Anderson, Indiana, United States, 46016
        • Research Site
      • Fort Wayne, Indiana, United States, 46845
        • Research Site
      • Indianapolis, Indiana, United States, 46202
        • Research Site
    • Iowa
      • Ames, Iowa, United States, 50010
        • Research Site
      • Iowa City, Iowa, United States, 52242
        • Research Site
    • Kentucky
      • Paducah, Kentucky, United States, 42003
        • Research Site
    • Louisiana
      • New Orleans, Louisiana, United States, 70121
        • Research Site
    • Maine
      • Scarborough, Maine, United States, 04074
        • Research Site
    • Maryland
      • Baltimore, Maryland, United States, 21204
        • Research Site
      • Baltimore, Maryland, United States, 21237
        • Research Site
      • Baltimore, Maryland, United States, 21229
        • Research Site
      • Bethesda, Maryland, United States, 20817
        • Research Site
      • Westminster, Maryland, United States, 21157
        • Research Site
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Research Site
      • Boston, Massachusetts, United States, 02215
        • Research Site
      • Danvers, Massachusetts, United States, 01923
        • Research Site
      • Fairhaven, Massachusetts, United States, 02719
        • Research Site
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Research Site
      • Lansing, Michigan, United States, 48910
        • Research Site
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • Research Site
    • Missouri
      • Springfield, Missouri, United States, 65806
        • Research Site
    • Montana
      • Billings, Montana, United States, 59101
        • Research Site
    • Nebraska
      • Lincoln, Nebraska, United States, 68506
        • Research Site
      • Omaha, Nebraska, United States, 68198
        • Research Site
    • Nevada
      • North Las Vegas, Nevada, United States, 89086
        • Research Site
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Research Site
    • New York
      • Lake Success, New York, United States, 11042
        • Research Site
      • New York, New York, United States, 10021
        • Research Site
      • Rochester, New York, United States, 14621
        • Research Site
    • North Carolina
      • Fayetteville, North Carolina, United States, 28304
        • Research Site
      • Goldsboro, North Carolina, United States, 27534
        • Research Site
      • High Point, North Carolina, United States, 27262
        • Research Site
    • North Dakota
      • Bismarck, North Dakota, United States, 58501
        • Research Site
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73120-8345
        • Research Site
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
        • Research Site
      • Philadelphia, Pennsylvania, United States, 19106
        • Research Site
      • Philadelphia, Pennsylvania, United States, 19140
        • Research Site
      • Philadelphia, Pennsylvania, United States, 19141
        • Research Site
      • West Reading, Pennsylvania, United States, 19611
        • Research Site
    • South Carolina
      • Charleston, South Carolina, United States, 29406
        • Research Site
      • Charleston, South Carolina, United States, 29414
        • Research Site
      • Greenville, South Carolina, United States, 29615
        • Research Site
    • South Dakota
      • Aberdeen, South Dakota, United States, 57401
        • Research Site
      • Rapid City, South Dakota, United States, 57701
        • Research Site
      • Sioux Falls, South Dakota, United States, 57105
        • Research Site
      • Watertown, South Dakota, United States, 57201
        • Research Site
    • Tennessee
      • Memphis, Tennessee, United States, 38120
        • Research Site
    • Texas
      • Houston, Texas, United States, 77030
        • Research Site
      • Lubbock, Texas, United States, 79415
        • Research Site
    • Utah
      • Salt Lake City, Utah, United States, 84106
        • Research Site
    • Virginia
      • Christiansburg, Virginia, United States, 24073
        • Research Site
    • Washington
      • Spokane, Washington, United States, 99208
        • Research Site
      • Tacoma, Washington, United States, 98405
        • Research Site
    • West Virginia
      • Morgantown, West Virginia, United States, 26506
        • Research Site
    • Wisconsin
      • Minocqua, Wisconsin, United States, 54548
        • Research Site
      • Wauwatosa, Wisconsin, United States, 53226
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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:
  • Zometa®
Administered by subcutaneous injection once every 4 weeks.
Administered by subcutaneous injection once every 4 weeks.
Other Names:
  • AMG 162
  • XGEVA®
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:
  • AMG 162
  • XGEVA®
Administered by subcutaneous injection once every 4 weeks.
Other Names:
  • AMG 162
  • XGEVA®
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

This is where you will find people and organizations involved with this study.

Sponsor

Collaborators

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

May 17, 2012

Primary Completion (ACTUAL)

July 19, 2016

Study Completion (ACTUAL)

March 29, 2019

Study Registration Dates

First Submitted

April 28, 2011

First Submitted That Met QC Criteria

April 28, 2011

First Posted (ESTIMATE)

April 29, 2011

Study Record Updates

Last Update Posted (ACTUAL)

November 8, 2022

Last Update Submitted That Met QC Criteria

November 4, 2022

Last Verified

November 1, 2022

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

IPD Sharing Time Frame

Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.

IPD Sharing Access Criteria

Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.

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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