Evaluation of New or Worsening Lens Opacifications in Men With Non-metastatic Prostate Cancer Receiving Denosumab for Bone Loss

A Double-blind, Placebo-controlled Study to Evaluate New or Worsening Lens Opacifications in Subjects With Non-metastatic Prostate Cancer Receiving Denosumab for Bone Loss Due to Androgen-Deprivation Therapy

This is a phase 3, randomized, double-blind, placebo-controlled study to evaluate new or worsening lens opacifications in men with non-metastatic prostate cancer receiving denosumab for bone loss due to androgen deprivation therapy.

Study Overview

• Status: Completed
• Conditions: Cancer; Cataract; Prostate Cancer; Osteoporosis; Osteopenia; Low Bone Mineral Density
• Intervention / Treatment: Biological: Placebo; Biological: Denosumab

• Study Type: Interventional
• Enrollment (Actual): 769
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Wahroonga, New South Wales, Australia, 2076
      • Research Site
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Research Site
  • Victoria
    • Bentleigh East, Victoria, Australia, 3165
      • Research Site
    • Ringwood East, Victoria, Australia, 3135
      • Research Site
• Bulgaria
  • Pleven, Bulgaria, 5800
    • Research Site
  • Plovdiv, Bulgaria, 4004
    • Research Site
  • Sofia, Bulgaria, 1784
    • Research Site
• Canada
  • British Columbia
    • Kelowna, British Columbia, Canada, V1W 4V5
      • Research Site
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Research Site
    • Victoria, British Columbia, Canada, V8T 5G1
      • Research Site
    • Victoria, British Columbia, Canada, V8V 3N1
      • Research Site
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Research Site
  • Ontario
    • Barrie, Ontario, Canada, L4M 7G1
      • Research Site
    • Brampton, Ontario, Canada, L6T 4S5
      • Research Site
    • Brantford, Ontario, Canada, N3S 6T6
      • Research Site
    • Burlington, Ontario, Canada, L7N 3V2
      • Research Site
    • Guelph, Ontario, Canada, N1H 5J1
      • Research Site
    • Kitchener, Ontario, Canada, N2N 2B9
      • Research Site
    • London, Ontario, Canada, N6A 4G5
      • Research Site
    • Newmarket, Ontario, Canada, L3X 1W1
      • Research Site
    • North Bay, Ontario, Canada, P1B 7K8
      • Research Site
    • North York, Ontario, Canada, M3B 3S6
      • Research Site
    • Oakville, Ontario, Canada, L6H 3P1
      • Research Site
    • Scarborough, Ontario, Canada, M1P 2T7
      • Research Site
    • Toronto, Ontario, Canada, M5G 2M9
      • Research Site
    • Toronto, Ontario, Canada, M4N 3M5
      • Research Site
    • Toronto, Ontario, Canada, M6A 3B5
      • Research Site
  • Quebec
    • Laval, Quebec, Canada, H7G 2E6
      • Research Site
    • Montreal, Quebec, Canada, H2L 4M1
      • Research Site
• Czechia
  • Benesov, Czechia, 256 01
    • Research Site
  • Brno, Czechia, 612 00
    • Research Site
  • Hradec Kralove, Czechia, 500 05
    • Research Site
  • Jindrichuv Hradec, Czechia, 377 01
    • Research Site
  • Kromeriz, Czechia, 767 55
    • Research Site
  • Novy Jicin, Czechia, 741 01
    • Research Site
  • Olomouc, Czechia, 775 20
    • Research Site
  • Plzen, Czechia, 305 99
    • Research Site
  • Praha 2, Czechia, 120 00
    • Research Site
  • Praha 4, Czechia, 140 00
    • Research Site
  • Praha 6, Czechia, 160 00
    • Research Site
  • Usti nad Labem, Czechia, 401 13
    • Research Site
  • Zlin, Czechia, 760 01
    • Research Site
• France
  • Lyon Cédex 3, France, 69437
    • Research Site
  • Paris Cedex 5, France, 75248
    • Research Site
• Greece
  • Alexandroupoli, Greece, 68100
    • Research Site
  • Athens, Greece, 11527
    • Research Site
  • Athens, Greece, 11522
    • Research Site
  • Athens, Greece, 11526
    • Research Site
  • Heraklion, Greece, 71110
    • Research Site
  • Larissa, Greece, 41110
    • Research Site
  • Patra, Greece, 26504
    • Research Site
  • Thessaloniki, Greece, 54622
    • Research Site
  • Thessaloniki, Greece, 56429
    • Research Site
• Hungary
  • Baja, Hungary, 6500
    • Research Site
  • Budapest, Hungary, 1204
    • Research Site
  • Budapest, Hungary, 1036
    • Research Site
  • Budapest, Hungary, 1082
    • Research Site
  • Gyor, Hungary, 9023
    • Research Site
  • Miskolc, Hungary, 3526
    • Research Site
  • Nyiregyhaza, Hungary, 4400
    • Research Site
  • Szeged, Hungary, 6722
    • Research Site
• India
  • Gujarat
    • Ahmedabad, Gujarat, India, 380 009
      • Research Site
  • Karnataka
    • Bangalore, Karnataka, India, 560 027
      • Research Site
  • Maharashtra
    • Aurangabad, Maharashtra, India, 431 005
      • Research Site
    • Nashik, Maharashtra, India, 422 004
      • Research Site
  • Punjab
    • Ludhiana, Punjab, India, 141 008
      • Research Site
  • Tamil Nadu
    • Madurai, Tamil Nadu, India, 625 107
      • Research Site
  • West Bengal
    • Kolkata, West Bengal, India, 700 027
      • Research Site
• Latvia
  • Jelgava, Latvia, 3001
    • Research Site
  • Riga, Latvia, 1079
    • Research Site
  • Riga, Latvia, 1002
    • Research Site
• Mexico
  • Distrito Federal, Mexico, 01120
    • Research Site
  • Distrito Federal, Mexico, 11950
    • Research Site
• New Zealand
  • Christchurch, New Zealand, 8013
    • Research Site
  • Takapuna, North Shore City, New Zealand, 0622
    • Research Site
  • Tauranga, New Zealand, 3112
    • Research Site
  • Whangarei, New Zealand, 0112
    • Research Site
• Poland
  • Gdansk, Poland, 80-952
    • Research Site
  • Gdansk, Poland, 80-180
    • Research Site
  • Gdynia, Poland, 81-423
    • Research Site
  • Gdynia, Poland, 81-366
    • Research Site
  • Katowice, Poland, 40-857
    • Research Site
  • Myslowice, Poland, 41-400
    • Research Site
  • Opole, Poland, 45-086
    • Research Site
  • Poznan, Poland, 61-866
    • Research Site
  • Rzeszow, Poland, 35-021
    • Research Site
  • Siedlce, Poland, 08-110
    • Research Site
  • Slupsk, Poland, 76-200
    • Research Site
  • Szczecin, Poland, 70-111
    • Research Site
  • Warszawa, Poland, 02-781
    • Research Site
  • Warszawa, Poland, 00-631
    • Research Site
  • Warszawa, Poland, 02-005
    • Research Site
  • Wroclaw, Poland, 50-044
    • Research Site
• Russian Federation
  • Ivanovo, Russian Federation, 153013
    • Research Site
  • Moscow, Russian Federation, 115478
    • Research Site
  • Moscow, Russian Federation, 125284
    • Research Site
  • Moscow, Russian Federation, 105425
    • Research Site
  • Nizhny Novgorod, Russian Federation, 603126
    • Research Site
  • Rostov-na-Donu, Russian Federation, 344022
    • Research Site
• Slovakia
  • Bratislava, Slovakia, 851 05
    • Research Site
  • Kosice, Slovakia, 040 01
    • Research Site
  • Kosice, Slovakia, 040 11
    • Research Site
  • Kosice, Slovakia, 040 23
    • Research Site
  • Martin, Slovakia, 036 59
    • Research Site
  • Nitra, Slovakia, 949 01
    • Research Site
  • Trencin, Slovakia, 911 01
    • Research Site
• Slovenia
  • Celje, Slovenia, 3000
    • Research Site
  • Ljubljana, Slovenia, 1525
    • Research Site
  • Slovenj Gradec, Slovenia, 2380
    • Research Site
• South Africa
  • George, South Africa, 6530
    • Research Site
  • Kempton Park, South Africa, 1619
    • Research Site
  • Port Elizabeth, South Africa, 6001
    • Research Site
  • Tygerberg, South Africa, 7505
    • Research Site
  • Western Cape
    • Paarl, Western Cape, South Africa, 7646
      • Research Site
• Ukraine
  • Chernivtsi, Ukraine, 58002
    • Research Site
  • Dnipropetrovsk, Ukraine, 49005
    • Research Site
  • Kharkiv, Ukraine, 61037
    • Research Site
  • Kyiv, Ukraine, 02125
    • Research Site
  • Uzhgorod, Ukraine, 88000
    • Research Site
  • Zaporizhzhya, Ukraine, 69600
    • Research Site
• United States
  • California
    • Anaheim, California, United States, 92801
      • Research Site
    • Laguna Hills, California, United States, 92653
      • Research Site
    • Murrieta, California, United States, 92562
      • Research Site
    • San Diego, California, United States, 92120
      • Research Site
    • San Diego, California, United States, 92123
      • Research Site
    • San Diego, California, United States, 92103
      • Research Site
    • San Luis Obispo, California, United States, 93405
      • Research Site
  • Colorado
    • Denver, Colorado, United States, 80211
      • Research Site
    • Denver, Colorado, United States, 80204
      • Research Site
    • Englewood, Colorado, United States, 80113
      • Research Site
  • Connecticut
    • Middlebury, Connecticut, United States, 06762
      • Research Site
    • New Britain, Connecticut, United States, 06052
      • Research Site
  • Florida
    • Trinity, Florida, United States, 34655
      • Research Site
  • Idaho
    • Coeur d'Alene, Idaho, United States, 83814
      • Research Site
  • Indiana
    • Greenwood, Indiana, United States, 46143
      • Research Site
  • Iowa
    • West Des Moines, Iowa, United States, 50266
      • Research Site
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Research Site
  • Louisiana
    • Shreveport, Louisiana, United States, 71106
      • Research Site
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Research Site
    • Baltimore, Maryland, United States, 21201
      • Research Site
    • Greenbelt, Maryland, United States, 20770
      • Research Site
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Research Site
  • Minnesota
    • Sartell, Minnesota, United States, 56377
      • Research Site
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Research Site
  • Montana
    • Missoula, Montana, United States, 59808
      • Research Site
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Research Site
    • Omaha, Nebraska, United States, 68105-1850
      • Research Site
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Research Site
    • Bricktown, New Jersey, United States, 08724
      • Research Site
    • Englewood, New Jersey, United States, 07631
      • Research Site
    • Lawrenceville, New Jersey, United States, 08648
      • Research Site
    • Mount Laurel, New Jersey, United States, 08054
      • Research Site
  • New York
    • Albany, New York, United States, 12208
      • Research Site
    • Garden City, New York, United States, 11530
      • Research Site
    • Kingston, New York, United States, 12401
      • Research Site
    • New York, New York, United States, 10021
      • Research Site
    • Poughkeepsie, New York, United States, 12601
      • Research Site
    • Syracuse, New York, United States, 13210
      • Research Site
  • North Carolina
    • Gastonia, North Carolina, United States, 28054
      • Research Site
    • Greenville, North Carolina, United States, 27834
      • Research Site
  • Ohio
    • Cincinnati, Ohio, United States, 45212
      • Research Site
  • Pennsylvania
    • Bala-Cynwyd, Pennsylvania, United States, 19004
      • Research Site
    • Lancaster, Pennsylvania, United States, 17604
      • Research Site
    • Philadelphia, Pennsylvania, United States, 19107
      • Research Site
  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29572
      • Research Site
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Research Site
  • Texas
    • Austin, Texas, United States, 78759
      • Research Site
    • Dallas, Texas, United States, 75231
      • Research Site
    • San Antonio, Texas, United States, 78229
      • Research Site
    • Temple, Texas, United States, 76508
      • Research Site
  • Virginia
    • Richmond, Virginia, United States, 23235
      • Research Site
    • Salem, Virginia, United States, 24153
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Men ≥ 30 years of age with non-metastatic prostate cancer, having undergone bilateral orchiectomy or initiated androgen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) agonists and is expected to continue on ADT for at least 12 months
• Adequate visual accuracy allowing eye testing
• Bone Mineral Density (BMD) requirements: Osteopenia if under 70 years of age; Osteopenia or normal BMD if over 70 years of age
• Signed informed consent

Exclusion Criteria:

• Previous surgery for cataracts in both eyes, current diagnosis of cataracts, cataracts surgery foreseen in the near future, or ocular disease leading to visual loss
• Diagnosis of osteoporosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants received placebo administered by subcutaneous injection on Day 1 and at Month 6.	Biological: Placebo; Prefilled syringe for subcutaneous (SC) injection
Experimental: Denosumab; Participants received denosumab 60 mg administered by subcutaneous injection on Day 1 and at Month 6.	Biological: Denosumab; Prefilled syringe for subcutaneous (SC) injection administered at a dose of 60 mg; Other Names: Prolia®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Lens Opacification Event Development or Progression by Month 12	The Lens Opacities Classification System III (LOCS III) is a slit lamp based opacification grading method. Photographs of slit lamp cross-sections of the lens are used as references for grading nuclear opalescence (NO) and nuclear color (NC), and photographs of the lens seen by retroillumination are used as references for grading cortical (C) and posterior subcapsular (P) cataract. Opacification severity is graded on a decimal scale, scores can range from 0.1 to 6.9 for NO and NC and from 0.1 to 5.9 for C and P. For each opacification type the higher grading scores indicate greater severity. Lens opacification event development or progression by month 12 was based on a change of ≥ 1.0 in P, ≥ 1.0 in C, or ≥ 0.7 in NO in the LOCS III score from baseline.	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participant With Lens Opacification Event Development or Progression by Month 12 Based on a Change of ≥ 1.5 in P, ≥ 1.5 in C, or ≥ 1.5 in NO in the LOCS III Score	The Lens Opacities Classification System III (LOCS III) is a slit lamp based opacification grading method. Photographs of slit lamp cross-sections of the lens are used as references for grading nuclear opalescence (NO) and nuclear color (NC), and photographs of the lens seen by retroillumination are used as references for grading cortical (C) and posterior subcapsular (P) cataract. Opacification severity is graded on a decimal scale, scores can range from 0.1 to 6.9 for NO and NC and from 0.1 to 5.9 for C and P. For each opacification type the higher grading scores indicate greater severity. Lens opacification event development or progression by month 12 was based on a change ≥ 1.5 in P, ≥ 1.5 in C, or ≥ 1.5 in NO in the LOCS III score from baseline.	12 months
Percentage of Participants With Lens Opacification Event Development or Progression by Month 6	The Lens Opacities Classification System III (LOCS III) is a slit lamp based opacification grading method. Photographs of slit lamp cross-sections of the lens are used as references for grading nuclear opalescence (NO) and nuclear color (NC), and photographs of the lens seen by retroillumination are used as references for grading cortical (C) and posterior subcapsular (P) cataract. Opacification severity is graded on a decimal scale, scores can range from 0.1 to 6.9 for NO and NC and from 0.1 to 5.9 for C and P. For each opacification type the higher grading scores indicate greater severity. Lens opacification event development or progression by month 6 was based on a change of ≥ 1.0 in P, ≥ 1.0 in C, or ≥ 0.7 in NO in the LOCS III score from baseline.	6 months
Percentage of Participants With Confirmed Lens Opacification Event Development or Progression by Month 12	The Lens Opacities Classification System III (LOCS III) is a slit lamp based opacification grading method. Photographs of slit lamp cross-sections of the lens are used as references for grading nuclear opalescence (NO) and nuclear color (NC), and photographs of the lens seen by retroillumination are used as references for grading cortical (C) and posterior subcapsular (P) cataract. Opacification severity is graded on a decimal scale, scores can range from 0.1 to 6.9 for NO and NC and from 0.1 to 5.9 for C and P. For each opacification type the higher grading scores indicate greater severity. Lens opacification event development or progression by month 12 was based on a change of ≥ 1.0 in P, ≥ 1.0 in C, or ≥ 0.7 in NO in the LOCS III score from baseline. A confirmed lens opacification event development or progression was defined as 2 directly subsequent events per protocol assessments at the same location (P, C, NO) using LOCS III as above.	12 months
Percentage of Participants With a Decrease From Baseline in Best Corrected Visual Acuity (BCVA) of ≥ 10 Letters	The best corrected visual acuity (BCVA) is the best vision one can achieve with correction (such as eye glasses) as measured on an eye chart. BCVA was assessed by a trained ophthalmologist using the Early Treatment Diabetic Retinopathy Study (ETDRS) eye chart at 4 meters. The modified University of Crete ETDRS chart was used in Ukraine, Greece, Russia and Bulgaria, which do not use the Roman alphabet. The 2000 series revised ETDRS chart was used to assess the change in all other countries. The letter score was calculated based on the number of letters that were correctly identified; higher letter scores correspond to better visual acuity.	Baseline and Months 3, 6, 9 and 12
Change From Baseline in Refraction Needed to Achieve BCVA	Refraction error was measured using a phoropter. The change from baseline in spherical refraction error needed to achieve BCVA is reported.	Baseline and months 3, 6, 9, and 12
Number of Participants With Adverse Events	Adverse events (AEs) were assessed for severity by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) severity grading scale, version 3.0, where Grade 1 = Mild AE, Grade 2 = Moderate AE, Grade 3 = Severe AE, Grade 4 =Life-threatening AE and Grade 5 = Death due to AE. Treatment-related AEs (TRAEs) include only events for which the investigator indicated there was a reasonable possibility they may have been caused by the study drug.	12 months

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2009
• Primary Completion (Actual): May 12, 2016
• Study Completion (Actual): May 12, 2016

Study Registration Dates

• First Submitted: June 18, 2009
• First Submitted That Met QC Criteria: June 18, 2009
• First Posted (Estimate): June 22, 2009

Study Record Updates

• Last Update Posted (Actual): May 30, 2017
• Last Update Submitted That Met QC Criteria: April 19, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: Androgen Deprivation Therapy; Bone Loss; Lens Opacification; Non-metastatic prostate cancer
• Additional Relevant MeSH Terms: Metabolic Diseases; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Eye Diseases; Genital Neoplasms, Male; Prostatic Diseases; Musculoskeletal Diseases; Bone Diseases; Lens Diseases; Prostatic Neoplasms; Cataract; Osteoporosis; Bone Diseases, Metabolic; Physiological Effects of Drugs; Bone Density Conservation Agents; Denosumab
• Other Study ID Numbers: 20080560; 2009-012076-26 (EudraCT Number)