Know Cancer

forgot password

A Randomized Double-Blind, Placebo-Controlled Phase III Study of Early Versus Standard Zoledronic Acid to Prevent Skeletal Related Events in Men With Prostate Cancer Metastatic to Bone

Phase 3
18 Years
Open (Enrolling)
Metastatic Cancer, Prostate Cancer

Thank you

Trial Information

A Randomized Double-Blind, Placebo-Controlled Phase III Study of Early Versus Standard Zoledronic Acid to Prevent Skeletal Related Events in Men With Prostate Cancer Metastatic to Bone



- Compare the time to first skeletal-related events in patients with prostate cancer and
bone metastases undergoing androgen deprivation therapy when treated with zoledronate
vs placebo.


- Compare the overall and progression-free survival of patients treated with these

- Compare the toxic effects in patients treated with these regimens.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study followed
by an open-label study. Patients are stratified according to ECOG performance status (0-1 vs
2), prior skeletal-related event (no vs yes), and serum alkaline phosphatase (< upper limit
of normal [ULN] vs ≥ ULN). Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive zoledronate IV over 15 minutes on day 1.

- Arm II: Patients receive placebo IV over 15 minutes on day 1. In both arms, courses
repeat every 4 weeks in the absence of disease progression or a skeletal-related event.
All patients receive concurrent androgen deprivation therapy. Patients also receive
oral calcium and cholecalciferol (vitamin D) supplements daily.

Patients progressing to androgen-independent prostate cancer proceed to open-label therapy
comprising zoledronate IV over 15 minutes on day 1. Courses repeat every 3 weeks in the
absence of disease progression or a skeletal-related event.

Patients are followed periodically for approximately 10 years after randomization.

PROJECTED ACCRUAL: A total of 680 patients (340 per treatment arm) will be accrued for this
study within 4 years.

Inclusion Criteria


- Histologically confirmed adenocarcinoma of the prostate

- No small cell, neuroendocrine, or transitional cell carcinomas

- At least 1 bone metastasis by bone scan, MRI, CT scan, or plain radiographs

- Indeterminate lesions should be confirmed by a second imaging method

- At least 1 bone metastasis with no prior irradiation

- Concurrent androgen deprivation therapy required, defined as any of the following:

- Bilateral orchiectomy

- Gonadotropin-releasing hormone (GnRH) agonist with or without an antiandrogen



- 18 and over

Performance status

- ECOG 0-2

Life expectancy

- Not specified


- Not specified


- Not specified


- Creatinine clearance ≥ 30 mL/min

- Corrected calcium ≥ 8.0 mg/dL and < 11.6 mg/dL


- Fertile patients must use effective contraception


Biologic therapy

- Concurrent standard biologic response modifiers allowed during open-label therapy


- Concurrent standard cytotoxic chemotherapy allowed during open-label therapy only

Endocrine therapy

- See Disease Characteristics

- Prior neoadjuvant and/or adjuvant hormonal therapy allowed provided duration of
therapy was no more than 6 months AND therapy was discontinued more than 6 months
before study entry

- No more than 6 months since initiation of any of the following hormonal therapies:

- Orchiectomy

- GnRH agonist (e.g., leuprolide, goserelin, or triptorelin)

- Estrogen therapy

- Antiandrogens (e.g., bicalutamide, flutamide, or nilutamide)

- Any other therapy known to lower testosterone levels or inhibit testosterone

- No intermittent androgen deprivation therapy except for patients concurrently
enrolled on SWOG-9346

- Concurrent palliative corticosteroids allowed during open-label therapy only

- Concurrent standard hormonal agents allowed during open-label therapy only


- See Disease Characteristics

- No prior radiopharmaceuticals

- At least 4 weeks since prior radiotherapy

- Concurrent standard radiotherapy to extraskeletal tumor sites allowed during
open-label therapy only


- See Disease Characteristics


- No prior bisphosphonates

- No prior denosumab

- No other concurrent agents expected to alter osteoclast activity (e.g., denosumab,
calcitonin, mithramycin, gallium nitrate, or any other bisphosphonate)

- Concurrent daily supplemental elemental calcium (500 mg) and a multivitamin
containing cholecalciferol (Vitamin D) (400 IU) OR a combination tablet containing
both recommended

- Concurrent standard marketed antineoplastic therapies allowed during open-label
therapy only

Type of Study:


Study Design:

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Time to first skeletal related event

Safety Issue:


Principal Investigator

Matthew R. Smith, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Massachusetts General Hospital


United States: Food and Drug Administration

Study ID:




Start Date:

January 2004

Completion Date:

Related Keywords:

  • Metastatic Cancer
  • Prostate Cancer
  • adenocarcinoma of the prostate
  • recurrent prostate cancer
  • stage IV prostate cancer
  • bone metastases
  • Neoplasm Metastasis
  • Neoplasms
  • Neoplasms, Second Primary
  • Prostatic Neoplasms



Roswell Park Cancer InstituteBuffalo, New York  14263
Cardinal Bernardin Cancer Center at Loyola University Medical CenterMaywood, Illinois  60153-5500
University of Chicago Cancer Research CenterChicago, Illinois  60637
CCOP - Missouri Valley Cancer ConsortiumOmaha, Nebraska  68131
CCOP - Carle Cancer CenterUrbana, Illinois  61801
CCOP - Metro-MinnesotaSaint Louis Park, Minnesota  55416
Veterans Affairs Medical Center - East OrangeEast Orange, New Jersey  07018-1095
Rush-Copley Cancer Care CenterAurora, Illinois  60507
Carle Cancer Center at Carle Foundation HospitalUrbana, Illinois  61801
Saint Anthony Memorial Health CentersMichigan City, Indiana  46360
Bronson Methodist HospitalKalamazoo, Michigan  49007
West Michigan Cancer CenterKalamazoo, Michigan  49007-3731
Borgess Medical CenterKalamazooaa, Michigan  49001
Fairview Ridges HospitalBurnsville, Minnesota  55337
Mercy and Unity Cancer Center at Mercy HospitalCoon Rapids, Minnesota  55433
Duluth Clinic Cancer Center - DuluthDuluth, Minnesota  55805-1983
CCOP - DuluthDuluth, Minnesota  55805
Miller - Dwan Medical CenterDuluth, Minnesota  55805
Fairview Southdale HospitalEdina, Minnesota  55435
Mercy and Unity Cancer Center at Unity HospitalFridley, Minnesota  55432
Hutchinson Area Health CareHutchinson, Minnesota  55350
Minnesota Oncology Hematology, PA - MaplewoodMaplewood, Minnesota  55109
HealthEast Cancer Care at St. John's HospitalMaplewood, Minnesota  55109
Hennepin County Medical Center - MinneapolisMinneapolis, Minnesota  55415
Virginia Piper Cancer Institute at Abbott - Northwestern HospitalMinneapolis, Minnesota  55407
Park Nicollet Cancer CenterSt. Louis Park, Minnesota  55416
Regions Hospital Cancer Care CenterSt. Paul, Minnesota  55101
United HospitalSt. Paul, Minnesota  55102
Ridgeview Medical CenterWaconia, Minnesota  55387
Minnesota Oncology Hematology, PA - WoodburyWoodbury, Minnesota  55125
MetroHealth Cancer Care Center at MetroHealth Medical CenterCleveland, Ohio  44109
St. Rita's Medical CenterLima, Ohio  45801
Memorial Hospital of South BendSouth Bend, Indiana  46601
CCOP - Montana Cancer ConsortiumBillings, Montana  59101
Mercy Hospital Cancer Center - ScrantonScranton, Pennsylvania  18501
CCOP - GreenvilleGreenville, South Carolina  29615
LDS HospitalSalt Lake City, Utah  84143
CCOP - Northern Indiana CR ConsortiumSouth Bend, Indiana  46601
Saint Joseph Regional Medical CenterSouth Bend, Indiana  46617
Holden Comprehensive Cancer Center at University of IowaIowa City, Iowa  52242-1002
Cancer Research Center of HawaiiHonolulu, Hawaii  96813
MBCCOP - LSU Health Sciences CenterNew Orleans, Louisiana  70112
Veterans Affairs Medical Center - HoustonHouston, Texas  77030
Utah Valley Regional Medical Center - ProvoProvo, Utah  84604
Veterans Affairs Medical Center - BuffaloBuffalo, New York  14215
Veterans Affairs Medical Center - SyracuseSyracuse, New York  13210
Louis A. Weiss Memorial HospitalChicago, Illinois  60640
Veterans Affairs Medical Center - BaltimoreBaltimore, Maryland  21201
Fletcher Allen Health Care - University Health Center CampusBurlington, Vermont  05401
St. Vincent Mercy Medical CenterToledo, Ohio  43608
Arkansas Cancer Research Center at University of Arkansas for Medical SciencesLittle Rock, Arkansas  72205
Josephine Ford Cancer Center at Henry Ford HospitalDetroit, Michigan  48202
Swedish Cancer Institute at Swedish Medical Center - First Hill CampusSeattle, Washington  98104
SUNY Downstate Medical CenterBrooklyn, New York  11203
CCOP - Toledo Community HospitalToledo, Ohio  43623-3456
Yale Cancer CenterNew Haven, Connecticut  06520-8028
SUNY Upstate Medical University HospitalSyracuse, New York  13210
Medical University of Ohio Cancer CenterToledo, Ohio  43614
Toledo HospitalToledo, Ohio  43606
Baylor University Medical Center - HoustonHouston, Texas  77030-2399
St. Vincent Hospital Regional Cancer CenterGreen Bay, Wisconsin  54307-3508
Green Bay Oncology, Limited - EscanabaEscanaba, Michigan  49431
Dickinson County Healthcare SystemIron Mountain, Michigan  49801
CCOP - Hematology-Oncology Associates of Central New YorkEast Syracuse, New York  13057
St. Mary's Hospital Medical Center - Green BayGreen Bay, Wisconsin  54303
Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer CenterGreen Bay, Wisconsin  54301-3526
Green Bay Oncology, Limited at St. Mary's HospitalGreen Bay, Wisconsin  54303
Bay Area Cancer Care Center at Bay Area Medical CenterMarinette, Wisconsin  54143
Green Bay Oncology, Limited - Oconto FallsOconto Falls, Wisconsin  54154
Green Bay Oncology, Limited - Sturgeon BaySturgeon Bay, Wisconsin  54235
Hematology-Oncology Centers of the Northern Rockies - BillingsBillings, Montana  59101
Big Sky OncologyGreat Falls, Montana  59405
St. Peter's HospitalHelena, Montana  59601
Kalispell Regional Medical CenterKalispell, Montana  59901
Glacier Oncology, PLLCKalispell, Montana  59901
Montana Cancer Center at St. Patrick Hospital and Health Sciences CenterMissoula, Montana  59802
Montana Cancer Specialists at Montana Cancer CenterMissoula, Montana  59802
American Fork HospitalAmerican Fork, Utah  84003
Logan Regional HospitalLogan, Utah  84321
Utah Cancer Specialists at UCS Cancer CenterSalt Lake City, Utah  84106
Olympic Hematology and OncologyBremerton, Washington  98310
Skagit Valley Hospital Cancer Care CenterMt. Vernon, Washington  98273
University Cancer Center at University of Washington Medical CenterSeattle, Washington  98195
Group Health Central HospitalSeattle, Washington  98104
North Puget Oncology at United General HospitalSedro-Wooley, Washington  98284
Cancer Care Northwest - Spokane SouthSpokane, Washington  99202
Veterans Affairs Medical Center - Loma Linda (Pettis)Loma Linda, California  92357
Veterans Affairs Medical Center - HinesHines, Illinois  60141
Greenebaum Cancer Center at University of Maryland Medical CenterBaltimore, Maryland  21201
UNMC Eppley Cancer Center at the University of Nebraska Medical CenterOmaha, Nebraska  68198-7680
New York Weill Cornell Cancer Center at Cornell UniversityNew York, New York  10021
UCSF Helen Diller Family Comprehensive Cancer CenterSan Francisco, California  94115
Lombardi Comprehensive Cancer Center at Georgetown University Medical CenterWashington, District of Columbia  20007
University of Illinois Cancer CenterChicago, Illinois  60612-7243
Indiana University Melvin and Bren Simon Cancer CenterIndianapolis, Indiana  46202-5289
Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer InstituteBoston, Massachusetts  02115
Siteman Cancer Center at Barnes-Jewish Hospital - Saint LouisSt. Louis, Missouri  63110
CCOP - Nevada Cancer Research FoundationLas Vegas, Nevada  89109-2306
University of New Mexico Cancer CenterAlbuquerque, New Mexico  87131-5636
Oklahoma University Cancer InstituteOklahoma City, Oklahoma  73104
Methodist Estabrook Cancer CenterOmaha, Nebraska  68114-4199
Huntsman Cancer Institute at University of UtahSalt Lake City, Utah  84112
Elkhart General HospitalElkhart, Indiana  46515
Howard Community HospitalKokomo, Indiana  46904
Lakeland Regional Cancer Care Center - St. JosephSt. Joseph, Michigan  49085
Veterans Affairs Medical Center - Chicago Westside HospitalChicago, Illinois  60612
University Medical Center of Southern NevadaLas Vegas, Nevada  89102
Salinas Valley Memorial HospitalSalinas, California  93901
Center for Cancer Therapy at LaPorte Hospital and Health ServicesLa Porte, Indiana  46350
Mary Bird Perkins Cancer Center - Baton RougeBaton Rouge, Louisiana  70809
Louisiana State University Health Sciences Center - MonroeMonroe, Louisiana  71210
Medical Center of Louisiana - New OrleansNew Orleans, Louisiana  70112
Feist-Weiller Cancer Center at Louisiana State University Health SciencesShreveport, Louisiana  71130-3932
Hickman Cancer Center at Bixby Medical CenterAdrian, Michigan  49221
Community Cancer Center of MonroeMonroe, Michigan  48162
Saint Francis Cancer Treatment Center at Saint Francis Memorial Health CenterGrand Island, Nebraska  68803
Immanuel Medical CenterOmaha, Nebraska  68122
Creighton University Medical CenterOmaha, Nebraska  68131-2197
Wood County Oncology CenterBowling Green, Ohio  43402
Lima Memorial HospitalLima, Ohio  45804
Northwest Ohio Oncology CenterMaumee, Ohio  43537
Toledo Clinic - OregonOregon, Ohio  43616
St. Charles Mercy HospitalOregon, Ohio  43616
North Coast Cancer Care, IncorporatedSandusky, Ohio  44870
Mercy Hospital of TiffinTiffin, Ohio  44883
Toledo Clinic, Incorporated - Main ClinicToledo, Ohio  43623
Fulton County Health CenterWauseon, Ohio  43567
Kaiser Permanente Health Care - PortlandPortland, Oregon  97232
Dixie Regional Medical Center - East CampusSaint George, Utah  84770
Mountainview MedicalBerlin, Vermont  05602
Minor and James Medical, PLLCSeattle, Washington  98104
Holy Family Memorial Medical Center Cancer Care CenterManitowoc, Wisconsin  54221-1450
Welch Cancer Center at Sheridan Memorial HospitalSheridan, Wyoming  82801
Massachusetts General HospitalBoston, Massachusetts  02114-2617
Hembree Mercy Cancer Center at St. Edward Mercy Medical CenterFt. Smith, Arkansas  72903
Cancer Resource Center - LincolnLincoln, Nebraska  68510
Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/CandlerSavannah, Georgia  31405
Michiana Hematology-Oncology, PC - ElkhartElkhart, Indiana  46514
Elkhart Clinic, LLCElkhart, Indiana  46514-2098
William N. Wishard Memorial HospitalIndianapolis, Indiana  46202
Michiana Hematology Oncology PC - La PorteLa Porte, Indiana  46350
Michiana Hematology-Oncology, PC - South BendMishawaka, Indiana  46545-1470
Michiana Hematology Oncology PC - PlymouthPlymouth, Indiana  46563
Covenant Cancer Treatment CenterWaterloo, Iowa  50702
Cotton-O'Neil Cancer CenterTopeka, Kansas  66606
Mercy Memorial Hospital - MonroeMonroe, Michigan  48162
Michiana Hematology Oncology PC - NilesNiles, Michigan  49120
Lakeside Cancer Specialists, PLLCSaint Joseph, Michigan  49085
Willmar Cancer Center at Rice Memorial HospitalWillmar, Minnesota  56201
Billings Clinic - DowntownBillings, Montana  59107-7000
Bozeman Deaconess Cancer CenterBozeman, Montana  59715
St. James Healthcare Cancer CareButte, Montana  59701
Great Falls Clinic - Main FacilityGreat Falls, Montana  59405
Sletten Cancer Institute at Benefis HealthcareGreat Falls, Montana  59405
Kalispell Medical Oncology at KRMCKalispell, Montana  59901
Alegant Health Cancer Center at Bergan Mercy Medical CenterOmaha, Nebraska  68124
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer CenterColumbus, Ohio  43210-1240
Fisher-Titus Medical CenterNorwalk, Ohio  44857
Flower Hospital Cancer CenterSylvania, Ohio  43560
St. Anne Mercy HospitalToledo, Ohio  43623
Susquehanna Cancer Center at Divine Providence HospitalWilliamsport, Pennsylvania  17701
Sandra L. Maxwell Cancer CenterCedar City, Utah  84720
Jon and Karen Huntsman Cancer Center at Intermountain Medical CenterMurray, Utah  84157
Val and Ann Browning Cancer Center at McKay-Dee Hospital CenterOgden, Utah  84403
Fredericksburg Oncology, IncorporatedFredericksburg, Virginia  22401
St. Joseph Cancer CenterBellingham, Washington  98225
Columbia Basin HematologyKennewick, Washington  99336
Evergreen Hematology and Oncology, PSSpokane, Washington  99218
Wenatchee Valley Medical CenterWenatchee, Washington  98801-2028
Ben Taub General HospitalHouston, Texas  77030
Robert and Beverly Lewis Family Cancer Care Center at Pomona Valley Hospital Medical CenterPomona, California  91767
Ruby L. Golleher Cancer Program at Presbyterian Intercommunity HospitalWhittier, California  90602
Queen's Cancer Institute at Queen's Medical CenterHonolulu, Hawaii  96813
Lowell General HospitalLowell, Massachusetts  01854
Good Samaritan Cancer Center at Good Samaritan HospitalKearney, Nebraska  68848-1990
Elliot Regional Cancer Center at Elliot HospitalManchester, New Hampshire  03103
Dana-Farber/Brigham and Women's Cancer CenterBoston, Massachusetts  02115
Duke Cancer InstituteDurham, North Carolina  27710
Kinston Medical SpecialistsKinston, North Carolina  28501
Greenville Hospital Cancer CenterGreenville, South Carolina  29605
MBCCOP - Meharry Medical College - NashvilleNashville, Tennessee  37208-3599
La Grange Memorial HospitalLa Grange, Illinois  60525
Rockwood Clinic Cancer Treatment CenterSpokane, Washington  99204-2967
University of Wisconcin Cancer Center at Aspirus Wausau HospitalWausau, Wisconsin  54401
Veterans Affairs Medical Center - Iowa CityIowa City, Iowa  52246-2208
Franklin & Edith Scarpa Regional Cancer Center at South Jersey HealthcareVineland, New Jersey  08360
St. Vincent Healthcare Cancer Care ServicesBillings, Montana  59101
Union Memorial HospitalBaltimore, Maryland  21218
Good Samaritan Hospital of MarylandBaltimore, Maryland  21239
Lynchburg Hematology-Oncology ClinicLynchburg, Virginia  24501
Providence Cancer Center at Providence HospitalMobile, Alabama  36608
Kapiolani Medical Center at Pali MomiAiea, Hawaii  96701
Kapiolani Medical Center for Women and ChildrenHonolulu, Hawaii  96826
Straub Clinic and Hospital, IncorporatedHonolulu, Hawaii  96813
Hawaii Medical Center - EastHonolulu, Hawaii  96817
OnCare Hawaii, Incorporated - KuakiniHonolulu, Hawaii  96817
OnCare Hawaii, Incorporated - LusitanaHonolulu, Hawaii  96813
Pacific Cancer Institute - MauiWailuku, Hawaii  96793
Elmhurst Memorial HospitalElmhurst, Illinois  60126
New Hampshire Oncology - Hematology, PA at Payson Center for Cancer CareConcord, New Hampshire  03301
Center for Cancer Care at Exeter HospitalExeter, New Hampshire  03833
New Hampshire Oncology - Hematology, PA - HooksettHooksett, New Hampshire  03106
Bay Area HospitalCoos Bay, Oregon  97420
Fountain Valley, California  92708
Veterans Affairs Medical Center - West HavenWest Haven, Connecticut  06516
Lovelace Medical Center - DowntownAlbuquerque, New Mexico  87102
Callahan Cancer Center at Great Plains Regional Medical CenterNorth Platte, Nebraska  69103
Provena St. Mary's Regional Cancer Center - KankakeeKankakee, Illinois  60901
Heartland Oncology and HematologyCouncil Bluffs, Iowa  51503
Dana-Farber Cancer Institute at LondonderryLondonderry, New Hampshire  03053
Southeastern Regional Medical CenterLumberton, North Carolina  28359
Granville Medical CenterOxford, North Carolina  27565
Duke Health Raleigh HospitalRaleigh, North Carolina  27609
Person Memorial HospitalRoxboro, North Carolina  27573
St. Luke's Texas Cancer Institute at St. Luke's Episcopal HospitalHouston, Texas  77030
Self Regional Cancer Center at Self Regional Medical CenterGreenwood, South Carolina  29646
Shore Regional Cancer Center at Memorial Hospital - EastonEaston, Maryland  21601
Humphrey Cancer Center at North Memorial Outpatient CenterRobbinsdale, Minnesota  55422-2900
Lakeview HospitalStillwater, Minnesota  55082
Kings County Hospital CenterBrooklyn, New York  11203
Kaiser Permanente Capital Area Medical Group - Shady Grove FacilityRockville, Maryland  20850
Nevada Cancer InstituteLas Vegas, Nevada  89135
Kaiser Permanente Mid-Atlantic Medical Group-Largo Medical FacilityLargo, Maryland  20774
Kaiser Permanente Medical Center - Fair OaksFairfax, Virginia  22033
Langlade Memorial HospitalAntigo, Wisconsin  54409
Lakeside HospitalOmaha, Nebraska  68130
Island Hospital Cancer Care Center at Island HospitalAnacortes, Washington  98221
Highline Medical Center Cancer CenterBurien, Washington  98166
Riverview UW Cancer Center at Riverview HospitalWisconsin Rapids, Wisconsin  54494
St. Nicholas HospitalSheboygan, Wisconsin  53081
Saint Helena HospitalSaint Helena, California  94574
Leesburg Regional Medical CenterLeesburg, Florida  34748
John R. Marsh Cancer Center at Washington County HospitalHagerstown, Maryland  21740
Wheaton Franciscan Cancer Care - St. JosephMilwaukee, Wisconsin  53210
Highland ClinicShreveport, Louisiana  71105
Kaiser Permanente at Capitol Hill Medical CenterWashington, District of Columbia  20002
Kaiser Permanente at Woodlawn Medical CenterBaltimore, Maryland  21244
Dana-Farber/Brigham and Women's Cancer Center at Milford Regional Medical CenterMilford, Massachusetts  01757