Zoledronate in Preventing Skeletal (Bone)-Related Events in Men Who Are Receiving Androgen Deprivation Therapy For Prostate Cancer and Bone Metastases

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

RATIONALE: Zoledronate may prevent or decrease skeletal (bone)-related events (such as pain or fractures) caused by bone metastases and androgen deprivation therapy. It is not yet known whether treatment with zoledronate is effective in preventing bone-related events in patients who have prostate cancer and bone metastases.

PURPOSE: This randomized phase III trial is studying how well zoledronate works in preventing bone-related events in patients who are receiving androgen deprivation therapy for prostate cancer and bone metastases.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer; Metastatic Cancer
• Intervention / Treatment: Drug: zoledronic acid; Other: placebo; Drug: androgen deprivation therapy; Drug: GnRH agonist; Dietary supplement: Calcium supplement; Dietary supplement: Vitamin D

Detailed Description

Zoledronic acid decreases the risk of skeletal related events in men with prostate cancer metastatic to bone and disease progression after primary hormonal therapy.

This study is designed to evaluate whether earlier treatment with zoledronic acid will further decrease the risk of skeletal related events. 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).

The primary objective of the study is to determine whether treatment with zoledronic acid at the time of initiation of androgen deprivation therapy for metastatic prostate cancer will delay the time to first skeletal related event. The secondary objective of the study is to compare the effect of treatment with zoledronic acid to placebo on overall survival (OS), progression-free survival (PFS) and toxicity in men receiving androgen deprivation therapy for metastatic prostate cancer.

Patients are randomized to 1 of 2 treatment arms. Treatment continues in the absence of disease progression or a skeletal-related event. All patients receive concurrent androgen deprivation therapy with a GnRH agonist. Patients also receive oral calcium and (vitamin D) supplements daily. Patients progressing to androgen-independent prostate cancer proceed to the open-label therapy with zoledronic acid IV. Treatment continues for 3 weeks in the absence of disease progression or the first skeletal-related event.

Patients are followed periodically for approximately 10 years after entry on the study.

• Study Type: Interventional
• Enrollment (Actual): 645
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute at University of Alberta
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 3P1
      • University of British Columbia
  • Ontario
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Program at London Health Sciences Centre
• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
      • Providence Cancer Center at Providence Hospital
  • Arkansas
    • Fort Smith, Arkansas, United States, 72903
      • Hembree Mercy Cancer Center at St. Edward Mercy Medical Center
    • Little Rock, Arkansas, United States, 72205
      • Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
  • California
    • Loma Linda, California, United States, 92357
      • Veterans Affairs Medical Center - Loma Linda (Pettis)
    • Pismo Beach, California, United States, 93449
    • Pomona, California, United States, 91767
      • Robert and Beverly Lewis Family Cancer Care Center at Pomona Valley Hospital Medical Center
    • Saint Helena, California, United States, 94574
      • Saint Helena Hospital
    • Salinas, California, United States, 93901
      • Salinas Valley Memorial Hospital
    • San Francisco, California, United States, 94115
      • UCSF Helen Diller Family Comprehensive Cancer Center
    • Whittier, California, United States, 90602
      • Ruby L. Golleher Cancer Program at Presbyterian Intercommunity Hospital
  • Connecticut
    • New Haven, Connecticut, United States, 06520-8028
      • Yale Cancer Center
    • West Haven, Connecticut, United States, 06516
      • Veterans Affairs Medical Center - West Haven
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
    • Washington, District of Columbia, United States, 20002
      • Kaiser Permanente at Capitol Hill Medical Center
  • Florida
    • Leesburg, Florida, United States, 34748
      • Leesburg Regional Medical Center
  • Georgia
    • Savannah, Georgia, United States, 31405
      • Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler
  • Hawaii
    • 'Aiea, Hawaii, United States, 96701
      • Kapiolani Medical Center at Pali Momi
    • Honolulu, Hawaii, United States, 96813
      • Cancer Research Center of Hawaii
    • Honolulu, Hawaii, United States, 96826
      • Kapiolani Medical Center for Women and Children
    • Honolulu, Hawaii, United States, 96813
      • OnCare Hawaii, Incorporated - Lusitana
    • Honolulu, Hawaii, United States, 96813
      • Queen's Cancer Institute at Queen's Medical Center
    • Honolulu, Hawaii, United States, 96813
      • Straub Clinic and Hospital, Incorporated
    • Honolulu, Hawaii, United States, 96817
      • Hawaii Medical Center - East
    • Honolulu, Hawaii, United States, 96817
      • OnCare Hawaii, Incorporated - Kuakini
    • Wailuku, Hawaii, United States, 96793
      • Pacific Cancer Institute - Maui
  • Illinois
    • Aurora, Illinois, United States, 60504
      • Rush-Copley Cancer Care Center
    • Chicago, Illinois, United States, 60637-1470
      • University of Chicago Cancer Research Center
    • Chicago, Illinois, United States, 60640
      • Louis A. Weiss Memorial Hospital
    • Chicago, Illinois, United States, 60612-7243
      • University of Illinois Cancer Center
    • Chicago, Illinois, United States, 60612
      • Veterans Affairs Medical Center - Chicago Westside Hospital
    • Elmhurst, Illinois, United States, 60126
      • Elmhurst Memorial Hospital
    • Hines, Illinois, United States, 60141
      • Veterans Affairs Medical Center - Hines
    • Kankakee, Illinois, United States, 60901
      • Provena St. Mary's Regional Cancer Center - Kankakee
    • La Grange, Illinois, United States, 60525
      • La Grange Memorial Hospital
    • Maywood, Illinois, United States, 60153
      • Cardinal Bernardin Cancer Center at Loyola University Medical Center
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center at Carle Foundation Hospital
    • Urbana, Illinois, United States, 61801
      • CCOP - Carle Cancer Center
  • Indiana
    • Elkhart, Indiana, United States, 46515
      • Elkhart General Hospital
    • Elkhart, Indiana, United States, 46514-2098
      • Elkhart Clinic, LLC
    • Elkhart, Indiana, United States, 46514
      • Michiana Hematology-Oncology, PC - Elkhart
    • Indianapolis, Indiana, United States, 46202-5289
      • Indiana University Melvin and Bren Simon Cancer Center
    • Indianapolis, Indiana, United States, 46202
      • William N. Wishard Memorial Hospital
    • Kokomo, Indiana, United States, 46904
      • Howard Community Hospital
    • La Porte, Indiana, United States, 46350
      • Center for Cancer Therapy at LaPorte Hospital and Health Services
    • Michigan City, Indiana, United States, 46360
      • Saint Anthony Memorial Health Centers
    • Mishawaka, Indiana, United States, 46545-1470
      • Michiana Hematology-Oncology, PC - South Bend
    • Mishawaka, Indiana, United States, 46545-1470
      • Saint Joseph Regional Medical Center
    • Plymouth, Indiana, United States, 46563
      • Michiana Hematology Oncology PC - Plymouth
    • South Bend, Indiana, United States, 46601
      • Memorial Hospital of South Bend
    • South Bend, Indiana, United States, 46601
      • CCOP - Northern Indiana CR Consortium
    • Westville, Indiana, United States, 46391
      • Michiana Hematology Oncology PC - La Porte
  • Iowa
    • Council Bluffs, Iowa, United States, 51503
      • Heartland Oncology and Hematology
    • Iowa City, Iowa, United States, 52242-1002
      • Holden Comprehensive Cancer Center at University of Iowa
    • Iowa City, Iowa, United States, 52246
      • Veterans Affairs Medical Center - Iowa City
    • Waterloo, Iowa, United States, 50702
      • Covenant Cancer Treatment Center
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Cotton-O'Neil Cancer Center
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Mary Bird Perkins Cancer Center - Baton Rouge
    • Monroe, Louisiana, United States, 71210
      • Louisiana State University Health Sciences Center - Monroe
    • New Orleans, Louisiana, United States, 70112
      • MBCCOP - LSU Health Sciences Center
    • New Orleans, Louisiana, United States, 70112
      • Medical Center of Louisiana - New Orleans
    • Shreveport, Louisiana, United States, 71105
      • Highland Clinic
    • Shreveport, Louisiana, United States, 71130-3932
      • Feist-Weiller Cancer Center at Louisiana State University Health Sciences
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Veterans Affairs Medical Center - Baltimore
    • Baltimore, Maryland, United States, 21218
      • Union Memorial Hospital
    • Baltimore, Maryland, United States, 21201
      • Greenebaum Cancer Center at University of Maryland Medical Center
    • Baltimore, Maryland, United States, 21239
      • Good Samaritan Hospital of Maryland
    • Baltimore, Maryland, United States, 21244
      • Kaiser Permanente at Woodlawn Medical Center
    • Easton, Maryland, United States, 21601
      • Shore Regional Cancer Center at Memorial Hospital - Easton
    • Hagerstown, Maryland, United States, 21740
      • John R. Marsh Cancer Center at Washington County Hospital
    • Largo, Maryland, United States, 20774
      • Kaiser Permanente Mid-Atlantic Medical Group-Largo Medical Facility
    • Rockville, Maryland, United States, 20850
      • Kaiser Permanente Capital Area Medical Group - Shady Grove Facility
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber/Brigham and Women's Cancer Center
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
    • Lowell, Massachusetts, United States, 01854
      • Lowell General Hospital
    • Milford, Massachusetts, United States, 01757
      • Dana-Farber/Brigham and Women's Cancer Center at Milford Regional Medical Center
  • Michigan
    • Adrian, Michigan, United States, 49221
      • Hickman Cancer Center at Bixby Medical Center
    • Detroit, Michigan, United States, 48202
      • Josephine Ford Cancer Center at Henry Ford Hospital
    • Escanaba, Michigan, United States, 49431
      • Green Bay Oncology, Limited - Escanaba
    • Iron Mountain, Michigan, United States, 49801
      • Dickinson County Healthcare System
    • Kalamazoo, Michigan, United States, 49007
      • Bronson Methodist Hospital
    • Kalamazoo, Michigan, United States, 49001
      • Borgess Medical Center
    • Kalamazoo, Michigan, United States, 49007-3731
      • West Michigan Cancer Center
    • Monroe, Michigan, United States, 48162
      • Community Cancer Center of Monroe
    • Monroe, Michigan, United States, 48162
      • Mercy Memorial Hospital - Monroe
    • Niles, Michigan, United States, 49120
      • Michiana Hematology Oncology PC - Niles
    • Saint Joseph, Michigan, United States, 49085
      • Lakeside Cancer Specialists, PLLC
    • Saint Joseph, Michigan, United States, 49085
      • Lakeland Regional Cancer Care Center - St. Joseph
  • Minnesota
    • Burnsville, Minnesota, United States, 55337
      • Fairview Ridges Hospital
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy and Unity Cancer Center at Mercy Hospital
    • Duluth, Minnesota, United States, 55805
      • CCOP - Duluth
    • Duluth, Minnesota, United States, 55805-1983
      • Duluth Clinic Cancer Center - Duluth
    • Duluth, Minnesota, United States, 55805
      • Miller - Dwan Medical Center
    • Edina, Minnesota, United States, 55435
      • Fairview Southdale Hospital
    • Fridley, Minnesota, United States, 55432
      • Mercy and Unity Cancer Center at Unity Hospital
    • Hutchinson, Minnesota, United States, 55350
      • Hutchinson Area Health Care
    • Maplewood, Minnesota, United States, 55109
      • Minnesota Oncology Hematology, PA - Maplewood
    • Maplewood, Minnesota, United States, 55109
      • HealthEast Cancer Care at St. John's Hospital
    • Minneapolis, Minnesota, United States, 55407
      • Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center - Minneapolis
    • Robbinsdale, Minnesota, United States, 55422-2900
      • Humphrey Cancer Center at North Memorial Outpatient Center
    • Saint Louis Park, Minnesota, United States, 55416
      • CCOP - Metro-Minnesota
    • Saint Louis Park, Minnesota, United States, 55416
      • Park Nicollet Cancer Center
    • Saint Paul, Minnesota, United States, 55102
      • United Hospital
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital Cancer Care Center
    • Stillwater, Minnesota, United States, 55082
      • Lakeview Hospital
    • Waconia, Minnesota, United States, 55387
      • Ridgeview Medical Center
    • Willmar, Minnesota, United States, 56201
      • Willmar Cancer Center at Rice Memorial Hospital
    • Woodbury, Minnesota, United States, 55125
      • Minnesota Oncology Hematology, PA - Woodbury
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
  • Montana
    • Billings, Montana, United States, 59101
      • CCOP - Montana Cancer Consortium
    • Billings, Montana, United States, 59101
      • St. Vincent Healthcare Cancer Care Services
    • Billings, Montana, United States, 59107-7000
      • Billings Clinic - Downtown
    • Billings, Montana, United States, 59102
      • Hematology-Oncology Centers of the Northern Rockies - Billings
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Cancer Center
    • Butte, Montana, United States, 59701
      • St. James Healthcare Cancer Care
    • Great Falls, Montana, United States, 59405
      • Great Falls Clinic - Main Facility
    • Great Falls, Montana, United States, 59405-5309
      • Big Sky Oncology
    • Great Falls, Montana, United States, 59405
      • Sletten Cancer Institute at Benefis Healthcare
    • Helena, Montana, United States, 59601
      • St. Peter's Hospital
    • Kalispell, Montana, United States, 59901
      • Kalispell Regional Medical Center
    • Kalispell, Montana, United States, 59901
      • Glacier Oncology, PLLC
    • Kalispell, Montana, United States, 59901
      • Kalispell Medical Oncology at KRMC
    • Missoula, Montana, United States, 59807-7877
      • Montana Cancer Specialists at Montana Cancer Center
    • Missoula, Montana, United States, 59807
      • Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
  • Nebraska
    • Grand Island, Nebraska, United States, 68803
      • Saint Francis Cancer Treatment Center at Saint Francis Memorial Health Center
    • Kearney, Nebraska, United States, 68848-1990
      • Good Samaritan Cancer Center at Good Samaritan Hospital
    • Lincoln, Nebraska, United States, 68510
      • Cancer Resource Center - Lincoln
    • North Platte, Nebraska, United States, 69103
      • Callahan Cancer Center at Great Plains Regional Medical Center
    • Omaha, Nebraska, United States, 68198-6805
      • UNMC Eppley Cancer Center at the University of Nebraska Medical Center
    • Omaha, Nebraska, United States, 68106
      • CCOP - Missouri Valley Cancer Consortium
    • Omaha, Nebraska, United States, 68122
      • Immanuel Medical Center
    • Omaha, Nebraska, United States, 68124
      • Alegant Health Cancer Center at Bergan Mercy Medical Center
    • Omaha, Nebraska, United States, 68131-2197
      • Creighton University Medical Center
    • Omaha, Nebraska, United States, 68114
      • Methodist Estabrook Cancer Center
    • Omaha, Nebraska, United States, 68130
      • Lakeside Hospital
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • University Medical Center of Southern Nevada
    • Las Vegas, Nevada, United States, 89135
      • Nevada Cancer Institute
    • Las Vegas, Nevada, United States, 89106
      • CCOP - Nevada Cancer Research Foundation
  • New Hampshire
    • Concord, New Hampshire, United States, 03301
      • New Hampshire Oncology - Hematology, PA at Payson Center for Cancer Care
    • Exeter, New Hampshire, United States, 03833
      • Center for Cancer Care at Exeter Hospital
    • Hooksett, New Hampshire, United States, 03106
      • New Hampshire Oncology - Hematology, PA - Hooksett
    • Londonderry, New Hampshire, United States, 03053
      • Dana-Farber Cancer Institute at Londonderry
    • Manchester, New Hampshire, United States, 03103
      • Elliot Regional Cancer Center at Elliot Hospital
  • New Jersey
    • East Orange, New Jersey, United States, 07018-1095
      • Veterans Affairs Medical Center - East Orange
    • Vineland, New Jersey, United States, 08360
      • Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131-5636
      • University of New Mexico Cancer Center
    • Albuquerque, New Mexico, United States, 87102
      • Lovelace Medical Center - Downtown
  • New York
    • Brooklyn, New York, United States, 11203
      • SUNY Downstate Medical Center
    • Brooklyn, New York, United States, 11203
      • Kings County Hospital Center
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute
    • Buffalo, New York, United States, 14215
      • Veterans Affairs Medical Center - Buffalo
    • East Syracuse, New York, United States, 13057
      • CCOP - Hematology-Oncology Associates of Central New York
    • New York, New York, United States, 10021
      • New York Weill Cornell Cancer Center at Cornell University
    • Syracuse, New York, United States, 13210
      • Veterans Affairs Medical Center - Syracuse
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Cancer Institute
    • Kinston, North Carolina, United States, 28501
      • Kinston Medical Specialists
    • Lumberton, North Carolina, United States, 28359
      • Southeastern Regional Medical Center
    • Oxford, North Carolina, United States, 27565
      • Granville Medical Center
    • Raleigh, North Carolina, United States, 27609
      • Duke Health Raleigh Hospital
    • Roxboro, North Carolina, United States, 27573
      • Person Memorial Hospital
  • Ohio
    • Bowling Green, Ohio, United States, 43402
      • Wood County Oncology Center
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Cancer Care Center at MetroHealth Medical Center
    • Columbus, Ohio, United States, 43210-1240
      • Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
    • Lima, Ohio, United States, 45804
      • Lima Memorial Hospital
    • Lima, Ohio, United States, 45801
      • St. Rita's Medical Center
    • Maumee, Ohio, United States, 43537-1839
      • Northwest Ohio Oncology Center
    • Norwalk, Ohio, United States, 44857
      • Fisher-Titus Medical Center
    • Oregon, Ohio, United States, 43616
      • St. Charles Mercy Hospital
    • Oregon, Ohio, United States, 43616
      • Toledo Clinic - Oregon
    • Sandusky, Ohio, United States, 44870
      • North Coast Cancer Care, Incorporated
    • Sylvania, Ohio, United States, 43560
      • Flower Hospital Cancer Center
    • Tiffin, Ohio, United States, 44883
      • Mercy Hospital of Tiffin
    • Toledo, Ohio, United States, 43608
      • St. Vincent Mercy Medical Center
    • Toledo, Ohio, United States, 43606
      • Toledo Hospital
    • Toledo, Ohio, United States, 43614
      • Medical University of Ohio Cancer Center
    • Toledo, Ohio, United States, 43617
      • CCOP - Toledo Community Hospital
    • Toledo, Ohio, United States, 43623
      • Toledo Clinic, Incorporated - Main Clinic
    • Toledo, Ohio, United States, 43623
      • St. Anne Mercy Hospital
    • Wauseon, Ohio, United States, 43567
      • Fulton County Health Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma University Cancer Institute
  • Oregon
    • Coos Bay, Oregon, United States, 97420
      • Bay Area Hospital
    • Portland, Oregon, United States, 97227
      • Kaiser Permanente Health Care - Portland
  • Pennsylvania
    • Scranton, Pennsylvania, United States, 18501
      • Mercy Hospital Cancer Center - Scranton
    • Williamsport, Pennsylvania, United States, 17701
      • Susquehanna Cancer Center at Divine Providence Hospital
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • CCOP - Greenville
    • Greenville, South Carolina, United States, 29605
      • Greenville Hospital Cancer Center
    • Greenwood, South Carolina, United States, 29646
      • Self Regional Cancer Center at Self Regional Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37208-3599
      • MBCCOP - Meharry Medical College - Nashville
  • Texas
    • Houston, Texas, United States, 77030
      • Ben Taub General Hospital
    • Houston, Texas, United States, 77030
      • Veterans Affairs Medical Center - Houston
    • Houston, Texas, United States, 77030
      • Baylor University Medical Center - Houston
    • Houston, Texas, United States, 77030
      • St. Luke's Texas Cancer Institute at St. Luke's Episcopal Hospital
  • Utah
    • American Fork, Utah, United States, 84003
      • American Fork Hospital
    • Cedar City, Utah, United States, 84720
      • Sandra L. Maxwell Cancer Center
    • Logan, Utah, United States, 84321
      • Logan Regional Hospital
    • Murray, Utah, United States, 84157
      • Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
    • Ogden, Utah, United States, 84403
      • Val and Ann Browning Cancer Center at McKay-Dee Hospital Center
    • Provo, Utah, United States, 84604
      • Utah Valley Regional Medical Center - Provo
    • Saint George, Utah, United States, 84770
      • Dixie Regional Medical Center - East Campus
    • Salt Lake City, Utah, United States, 84143
      • LDS Hospital
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute at University of Utah
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists at UCS Cancer Center
  • Vermont
    • Berlin, Vermont, United States, 05602
      • Mountainview Medical
    • Burlington, Vermont, United States, 05401
      • Fletcher Allen Health Care - University Health Center Campus
  • Virginia
    • Fairfax, Virginia, United States, 22033
      • Kaiser Permanente Medical Center - Fair Oaks
    • Fredericksburg, Virginia, United States, 22401
      • Fredericksburg Oncology, Incorporated
    • Lynchburg, Virginia, United States, 24501
      • Lynchburg Hematology-Oncology Clinic
  • Washington
    • Anacortes, Washington, United States, 98221
      • Island Hospital Cancer Care Center at Island Hospital
    • Bellingham, Washington, United States, 98225
      • St. Joseph Cancer Center
    • Bremerton, Washington, United States, 98310
      • Olympic Hematology and Oncology
    • Burien, Washington, United States, 98166
      • Highline Medical Center Cancer Center
    • Kennewick, Washington, United States, 99336
      • Columbia Basin Hematology
    • Mount Vernon, Washington, United States, 98274
      • Skagit Valley Hospital Cancer Care Center
    • Seattle, Washington, United States, 98104
      • Minor and James Medical, PLLC
    • Seattle, Washington, United States, 98112
      • Group Health Central Hospital
    • Seattle, Washington, United States, 98122-4307
      • Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
    • Seattle, Washington, United States, 98195
      • University Cancer Center at University of Washington Medical Center
    • Sedro-Woolley, Washington, United States, 98284
      • North Puget Oncology at United General Hospital
    • Spokane, Washington, United States, 99202
      • Cancer Care Northwest - Spokane South
    • Spokane, Washington, United States, 99218
      • Evergreen Hematology and Oncology, PS
    • Spokane, Washington, United States, 99204-2967
      • Rockwood Clinic Cancer Treatment Center
    • Wenatchee, Washington, United States, 98801-2028
      • Wenatchee Valley Medical Center
  • Wisconsin
    • Antigo, Wisconsin, United States, 54409
      • Langlade Memorial Hospital
    • Green Bay, Wisconsin, United States, 54307-3508
      • St. Vincent Hospital Regional Cancer Center
    • Green Bay, Wisconsin, United States, 54301-3526
      • Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center
    • Green Bay, Wisconsin, United States, 54303
      • Green Bay Oncology, Limited at St. Mary's Hospital
    • Green Bay, Wisconsin, United States, 54303
      • St. Mary's Hospital Medical Center - Green Bay
    • Manitowoc, Wisconsin, United States, 54221-1450
      • Holy Family Memorial Medical Center Cancer Care Center
    • Marinette, Wisconsin, United States, 54143
      • Bay Area Cancer Care Center at Bay Area Medical Center
    • Milwaukee, Wisconsin, United States, 53210
      • Wheaton Franciscan Cancer Care - St. Joseph
    • Oconto Falls, Wisconsin, United States, 54154
      • Green Bay Oncology, Limited - Oconto Falls
    • Sheboygan, Wisconsin, United States, 53081
      • St. Nicholas Hospital
    • Sturgeon Bay, Wisconsin, United States, 54235
      • Green Bay Oncology, Limited - Sturgeon Bay
    • Wausau, Wisconsin, United States, 54401
      • University of Wisconcin Cancer Center at Aspirus Wausau Hospital
    • Wisconsin Rapids, Wisconsin, United States, 54494
      • Riverview UW Cancer Center at Riverview Hospital
  • Wyoming
    • Sheridan, Wyoming, United States, 82801
      • Welch Cancer Center at Sheridan Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

1. Histologic Documentation: Histologic documentation of prostate adenocarcinoma. Patients with small cell, neuroendocrine, or transitional cell carcinomas are not eligible.
2. Staging: At least one bone metastasis by radiographic imaging (bone scan, magnetic resonance imaging, computed tomography, or plain radiographs). Indeterminate lesions should be confirmed by a second imaging method. Imaging to document bone metastases is to be completed either within 12 weeks before registration or within 12 weeks before initiating androgen deprivation therapy for bone metastases.

3. Hormone Therapy

   • While on this study, patients must receive androgen deprivation therapy (ADT) for treatment of prostate cancer. Androgen deprivation therapy may have begun prior to enrollment on this study; however patients must have initiated ADT ≤ 6 months prior to enrollment.
   • Androgen deprivation therapy is defined as bilateral orchiectomy or gonadotropin- releasing hormone (GnRH) agonist with or without an antiandrogen.
   • Patients treated with intermittent androgen deprivation therapy are not eligible except for patients concurrently enrolled in SWOG-9346/INT-0162/CALGB 9594, Phase III Study of Intermittent Androgen Deprivation in Patients with Stage D2 Prostate Cancer.

4. Prior Treatment:

   • Hormone therapy at any point prior to 6 months before enrollment is prohibited. This includes any of the following treatments:

     • orchiectomy,
     • GnRH agonist (e. g., leuprolide, goserelin, triptorelin),
     • estrogen therapy,
     • antiandrogen (e. g., bicalutamide, flutamide, nilutamide), or
     • any other therapy known to lower testosterone level or inhibit testosterone effect.
   • Prior neoadjuvant and/or adjuvant hormone therapy is allowed provided that the duration of hormone therapy was six months or less and the hormone therapy was discontinued more than 6 months prior to study entry.
   • No prior treatment with a bisphosphonate
   • No prior treatment with denosumab
   • No prior treatment with radiopharmaceuticals
   • ≥ 4 weeks since completion of prior radiation therapy with at least one bone metastasis present that has NOT been radiated.
5. ECOG (CTC) performance status 0-2
6. Age: ≥ 18 years

7. Required Initial Laboratory Data:

   • Calculated Creatinine Clearance ≥ 30 mL/min
   • Corrected serum calcium ≥ 8.0 mg/dL (2.00 mmol/L) and <11.6 mg/dL (2.90 mmol/L)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Zoledronic acid + androgen deprivation therapy; 4mg by IV over 15 minutes every 4 weeks in the absence of disease progression or the first skeletal-related event. Participants who progression on blinded treatment before having a skeletal event may continue on open label Zoledronic acid (4 mg by IV over 15 minutes every 3 weeks).	Drug: zoledronic acid; Given IV; Drug: androgen deprivation therapy; Patients concurrently enrolled on the Phase III study of intermittent androgen deprivation in patients with stage D2 prostate cancer will receive androgen deprivation therapy per SWOG-9346. All other patients will receive androgen deprivation therapy at a standard dose and schedule throughout the study.; Drug: GnRH agonist; Patients concurrently enrolled on the Phase III study of intermittent androgen deprivation in patients with stage D2 prostate cancer will receive the GnRH agonist per SWOG-9346. All other patients will receive GnRH agonist at a standard dose and schedule throughout the study.; Dietary supplement: Calcium supplement; Patients will receive 500 mg by mouth daily of a calcium supplement or a combination tablet containing approximately 500 mg elemental calcium and 400-500 IU vitamin D by mouth daily.; Dietary supplement: Vitamin D; Patients will receive a multivitamin tablet containing 400-500 IU vitamin D by mouth daily or a combination tablet containing approximately 500 mg elemental calcium and 400-500 IU vitamin D by mouth daily.
ACTIVE_COMPARATOR: Placebo + androgen deprivation therapy; Placebo bu IV over 15 minutes for 4 weeks in the absence of disease progression or the first skeletal-related event. Participants who progress on blinded treatment before having a skeletal event may continue on open label Zoledronic acid.	Other: placebo; Given IV; Drug: androgen deprivation therapy; Patients concurrently enrolled on the Phase III study of intermittent androgen deprivation in patients with stage D2 prostate cancer will receive androgen deprivation therapy per SWOG-9346. All other patients will receive androgen deprivation therapy at a standard dose and schedule throughout the study.; Drug: GnRH agonist; Patients concurrently enrolled on the Phase III study of intermittent androgen deprivation in patients with stage D2 prostate cancer will receive the GnRH agonist per SWOG-9346. All other patients will receive GnRH agonist at a standard dose and schedule throughout the study.; Dietary supplement: Calcium supplement; Patients will receive 500 mg by mouth daily of a calcium supplement or a combination tablet containing approximately 500 mg elemental calcium and 400-500 IU vitamin D by mouth daily.; Dietary supplement: Vitamin D; Patients will receive a multivitamin tablet containing 400-500 IU vitamin D by mouth daily or a combination tablet containing approximately 500 mg elemental calcium and 400-500 IU vitamin D by mouth daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to First Skeletal Related Event	Time to first skeletal related event (SRE) was defined as the time from randomization to first skeletal event. Skeletal events are defined as radiation to bone, clinical fracture, surgery to bone and spinal cord compression and death due to prostate cancer. The median with 95% CI was estimated using the Kaplan Meier method.	Up to 10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival (OS) was defined as the time from randomization to death of any cause. Surviving patients were censored at the date of last follow-up. The median OS with 95% CI was estimated using the Kaplan Meier method.	Up to 10 years
Progression-free Survival	Progression Free Survival (PFS) was defined as the time from registration until disease progression or death, whichever occurs first. The median PFS with 95% CI was estimated using the Kaplan-Meier method. Progression is defined as one or more of the following: new bone metastases, biochemical progression of PSA, treatment with radiation therapy while on treatment.	Up to 10 years

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI); Novartis Pharmaceuticals; Eastern Cooperative Oncology Group; NCIC Clinical Trials Group; Southwest Oncology Group
• Investigators: Study Chair: Matthew R. Smith, MD, PhD, Massachusetts General Hospital

Publications and helpful links

General Publications

• Smith MR, Halabi S, Ryan CJ, Hussain A, Vogelzang N, Stadler W, Hauke RJ, Monk JP, Saylor P, Bhoopalam N, Saad F, Sanford B, Kelly WK, Morris M, Small EJ. Randomized controlled trial of early zoledronic acid in men with castration-sensitive prostate cancer and bone metastases: results of CALGB 90202 (alliance). J Clin Oncol. 2014 Apr 10;32(11):1143-50. doi: 10.1200/JCO.2013.51.6500. Epub 2014 Mar 3.
• Jakob T, Tesfamariam YM, Macherey S, Kuhr K, Adams A, Monsef I, Heidenreich A, Skoetz N. Bisphosphonates or RANK-ligand-inhibitors for men with prostate cancer and bone metastases: a network meta-analysis. Cochrane Database Syst Rev. 2020 Dec 3;12(12):CD013020. doi: 10.1002/14651858.CD013020.pub2.

Helpful Links

• Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive.

Study record dates

Study Major Dates

• Study Start: January 1, 2004
• Primary Completion (ACTUAL): July 1, 2012
• Study Completion (ACTUAL): October 1, 2014

Study Registration Dates

• First Submitted: March 8, 2004
• First Submitted That Met QC Criteria: March 8, 2004
• First Posted (ESTIMATE): March 9, 2004

Study Record Updates

• Last Update Posted (ACTUAL): May 12, 2020
• Last Update Submitted That Met QC Criteria: April 28, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: stage IV prostate cancer; recurrent prostate cancer; bone metastases; adenocarcinoma of the prostate
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Calcium; Zoledronic Acid; Androgens
• Other Study ID Numbers: CALGB-90202; U10CA031946 (U.S. NIH Grant/Contract); CAN-NCIC-PRC2; CDR0000353209 (REGISTRY: NCI Physician Data Query)