Zoledronate in Preventing Skeletal (Bone)-Related Events in Men Who Are Receiving Androgen Deprivation Therapy For Prostate Cancer and Bone Metastases
Sponsor
Alliance for Clinical Trials in Oncology (Other)
Overall Status
Completed
CT.gov ID
NCT00079001
Collaborator
National Cancer Institute (NCI) (NIH), Southwest Oncology Group (Other), Eastern Cooperative Oncology Group (Other), NCIC Clinical Trials Group (Other), Novartis Pharmaceuticals (Industry)
645
241
2
129
2.7
0
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
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 Design
Study Type:
Interventional
Actual Enrollment
:
645 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
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
Study Start Date
:
Jan 1, 2004
Actual Primary Completion Date
:
Jul 1, 2012
Actual Study Completion Date
:
Oct 1, 2014
Arms and Interventions
| 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.
|
Outcome Measures
Primary Outcome Measures
- Time to First Skeletal Related Event [Up to 10 years]
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.
Secondary Outcome Measures
- Overall Survival [Up to 10 years]
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.
- Progression-free Survival [Up to 10 years]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
Male
Accepts Healthy Volunteers:
No
-
Histologic Documentation: Histologic documentation of prostate adenocarcinoma. Patients with small cell, neuroendocrine, or transitional cell carcinomas are not eligible.
-
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.
-
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.
- 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.
-
ECOG (CTC) performance status 0-2
-
Age: ≥ 18 years
-
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)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Providence Cancer Center at Providence Hospital | Mobile | Alabama | United States | 36608 |
| 2 | Hembree Mercy Cancer Center at St. Edward Mercy Medical Center | Fort Smith | Arkansas | United States | 72903 |
| 3 | Arkansas Cancer Research Center at University of Arkansas for Medical Sciences | Little Rock | Arkansas | United States | 72205 |
| 4 | Veterans Affairs Medical Center - Loma Linda (Pettis) | Loma Linda | California | United States | 92357 |
| 5 | Pismo Beach | California | United States | 93449 | |
| 6 | Robert and Beverly Lewis Family Cancer Care Center at Pomona Valley Hospital Medical Center | Pomona | California | United States | 91767 |
| 7 | Saint Helena Hospital | Saint Helena | California | United States | 94574 |
| 8 | Salinas Valley Memorial Hospital | Salinas | California | United States | 93901 |
| 9 | UCSF Helen Diller Family Comprehensive Cancer Center | San Francisco | California | United States | 94115 |
| 10 | Ruby L. Golleher Cancer Program at Presbyterian Intercommunity Hospital | Whittier | California | United States | 90602 |
| 11 | Yale Cancer Center | New Haven | Connecticut | United States | 06520-8028 |
| 12 | Veterans Affairs Medical Center - West Haven | West Haven | Connecticut | United States | 06516 |
| 13 | Kaiser Permanente at Capitol Hill Medical Center | Washington | District of Columbia | United States | 20002 |
| 14 | Lombardi Comprehensive Cancer Center at Georgetown University Medical Center | Washington | District of Columbia | United States | 20007 |
| 15 | Leesburg Regional Medical Center | Leesburg | Florida | United States | 34748 |
| 16 | Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler | Savannah | Georgia | United States | 31405 |
| 17 | Kapiolani Medical Center at Pali Momi | 'Aiea | Hawaii | United States | 96701 |
| 18 | Cancer Research Center of Hawaii | Honolulu | Hawaii | United States | 96813 |
| 19 | OnCare Hawaii, Incorporated - Lusitana | Honolulu | Hawaii | United States | 96813 |
| 20 | Queen's Cancer Institute at Queen's Medical Center | Honolulu | Hawaii | United States | 96813 |
| 21 | Straub Clinic and Hospital, Incorporated | Honolulu | Hawaii | United States | 96813 |
| 22 | Hawaii Medical Center - East | Honolulu | Hawaii | United States | 96817 |
| 23 | OnCare Hawaii, Incorporated - Kuakini | Honolulu | Hawaii | United States | 96817 |
| 24 | Kapiolani Medical Center for Women and Children | Honolulu | Hawaii | United States | 96826 |
| 25 | Pacific Cancer Institute - Maui | Wailuku | Hawaii | United States | 96793 |
| 26 | Rush-Copley Cancer Care Center | Aurora | Illinois | United States | 60504 |
| 27 | University of Illinois Cancer Center | Chicago | Illinois | United States | 60612-7243 |
| 28 | Veterans Affairs Medical Center - Chicago Westside Hospital | Chicago | Illinois | United States | 60612 |
| 29 | University of Chicago Cancer Research Center | Chicago | Illinois | United States | 60637-1470 |
| 30 | Louis A. Weiss Memorial Hospital | Chicago | Illinois | United States | 60640 |
| 31 | Elmhurst Memorial Hospital | Elmhurst | Illinois | United States | 60126 |
| 32 | Veterans Affairs Medical Center - Hines | Hines | Illinois | United States | 60141 |
| 33 | Provena St. Mary's Regional Cancer Center - Kankakee | Kankakee | Illinois | United States | 60901 |
| 34 | La Grange Memorial Hospital | La Grange | Illinois | United States | 60525 |
| 35 | Cardinal Bernardin Cancer Center at Loyola University Medical Center | Maywood | Illinois | United States | 60153 |
| 36 | Carle Cancer Center at Carle Foundation Hospital | Urbana | Illinois | United States | 61801 |
| 37 | CCOP - Carle Cancer Center | Urbana | Illinois | United States | 61801 |
| 38 | Elkhart Clinic, LLC | Elkhart | Indiana | United States | 46514-2098 |
| 39 | Michiana Hematology-Oncology, PC - Elkhart | Elkhart | Indiana | United States | 46514 |
| 40 | Elkhart General Hospital | Elkhart | Indiana | United States | 46515 |
| 41 | Indiana University Melvin and Bren Simon Cancer Center | Indianapolis | Indiana | United States | 46202-5289 |
| 42 | William N. Wishard Memorial Hospital | Indianapolis | Indiana | United States | 46202 |
| 43 | Howard Community Hospital | Kokomo | Indiana | United States | 46904 |
| 44 | Center for Cancer Therapy at LaPorte Hospital and Health Services | La Porte | Indiana | United States | 46350 |
| 45 | Saint Anthony Memorial Health Centers | Michigan City | Indiana | United States | 46360 |
| 46 | Michiana Hematology-Oncology, PC - South Bend | Mishawaka | Indiana | United States | 46545-1470 |
| 47 | Saint Joseph Regional Medical Center | Mishawaka | Indiana | United States | 46545-1470 |
| 48 | Michiana Hematology Oncology PC - Plymouth | Plymouth | Indiana | United States | 46563 |
| 49 | CCOP - Northern Indiana CR Consortium | South Bend | Indiana | United States | 46601 |
| 50 | Memorial Hospital of South Bend | South Bend | Indiana | United States | 46601 |
| 51 | Michiana Hematology Oncology PC - La Porte | Westville | Indiana | United States | 46391 |
| 52 | Heartland Oncology and Hematology | Council Bluffs | Iowa | United States | 51503 |
| 53 | Holden Comprehensive Cancer Center at University of Iowa | Iowa City | Iowa | United States | 52242-1002 |
| 54 | Veterans Affairs Medical Center - Iowa City | Iowa City | Iowa | United States | 52246 |
| 55 | Covenant Cancer Treatment Center | Waterloo | Iowa | United States | 50702 |
| 56 | Cotton-O'Neil Cancer Center | Topeka | Kansas | United States | 66606 |
| 57 | Mary Bird Perkins Cancer Center - Baton Rouge | Baton Rouge | Louisiana | United States | 70809 |
| 58 | Louisiana State University Health Sciences Center - Monroe | Monroe | Louisiana | United States | 71210 |
| 59 | MBCCOP - LSU Health Sciences Center | New Orleans | Louisiana | United States | 70112 |
| 60 | Medical Center of Louisiana - New Orleans | New Orleans | Louisiana | United States | 70112 |
| 61 | Highland Clinic | Shreveport | Louisiana | United States | 71105 |
| 62 | Feist-Weiller Cancer Center at Louisiana State University Health Sciences | Shreveport | Louisiana | United States | 71130-3932 |
| 63 | Greenebaum Cancer Center at University of Maryland Medical Center | Baltimore | Maryland | United States | 21201 |
| 64 | Veterans Affairs Medical Center - Baltimore | Baltimore | Maryland | United States | 21201 |
| 65 | Union Memorial Hospital | Baltimore | Maryland | United States | 21218 |
| 66 | Good Samaritan Hospital of Maryland | Baltimore | Maryland | United States | 21239 |
| 67 | Kaiser Permanente at Woodlawn Medical Center | Baltimore | Maryland | United States | 21244 |
| 68 | Shore Regional Cancer Center at Memorial Hospital - Easton | Easton | Maryland | United States | 21601 |
| 69 | John R. Marsh Cancer Center at Washington County Hospital | Hagerstown | Maryland | United States | 21740 |
| 70 | Kaiser Permanente Mid-Atlantic Medical Group-Largo Medical Facility | Largo | Maryland | United States | 20774 |
| 71 | Kaiser Permanente Capital Area Medical Group - Shady Grove Facility | Rockville | Maryland | United States | 20850 |
| 72 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
| 73 | Dana-Farber/Brigham and Women's Cancer Center | Boston | Massachusetts | United States | 02115 |
| 74 | Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute | Boston | Massachusetts | United States | 02115 |
| 75 | Lowell General Hospital | Lowell | Massachusetts | United States | 01854 |
| 76 | Dana-Farber/Brigham and Women's Cancer Center at Milford Regional Medical Center | Milford | Massachusetts | United States | 01757 |
| 77 | Hickman Cancer Center at Bixby Medical Center | Adrian | Michigan | United States | 49221 |
| 78 | Josephine Ford Cancer Center at Henry Ford Hospital | Detroit | Michigan | United States | 48202 |
| 79 | Green Bay Oncology, Limited - Escanaba | Escanaba | Michigan | United States | 49431 |
| 80 | Dickinson County Healthcare System | Iron Mountain | Michigan | United States | 49801 |
| 81 | Borgess Medical Center | Kalamazoo | Michigan | United States | 49001 |
| 82 | West Michigan Cancer Center | Kalamazoo | Michigan | United States | 49007-3731 |
| 83 | Bronson Methodist Hospital | Kalamazoo | Michigan | United States | 49007 |
| 84 | Community Cancer Center of Monroe | Monroe | Michigan | United States | 48162 |
| 85 | Mercy Memorial Hospital - Monroe | Monroe | Michigan | United States | 48162 |
| 86 | Michiana Hematology Oncology PC - Niles | Niles | Michigan | United States | 49120 |
| 87 | Lakeland Regional Cancer Care Center - St. Joseph | Saint Joseph | Michigan | United States | 49085 |
| 88 | Lakeside Cancer Specialists, PLLC | Saint Joseph | Michigan | United States | 49085 |
| 89 | Fairview Ridges Hospital | Burnsville | Minnesota | United States | 55337 |
| 90 | Mercy and Unity Cancer Center at Mercy Hospital | Coon Rapids | Minnesota | United States | 55433 |
| 91 | Duluth Clinic Cancer Center - Duluth | Duluth | Minnesota | United States | 55805-1983 |
| 92 | CCOP - Duluth | Duluth | Minnesota | United States | 55805 |
| 93 | Miller - Dwan Medical Center | Duluth | Minnesota | United States | 55805 |
| 94 | Fairview Southdale Hospital | Edina | Minnesota | United States | 55435 |
| 95 | Mercy and Unity Cancer Center at Unity Hospital | Fridley | Minnesota | United States | 55432 |
| 96 | Hutchinson Area Health Care | Hutchinson | Minnesota | United States | 55350 |
| 97 | HealthEast Cancer Care at St. John's Hospital | Maplewood | Minnesota | United States | 55109 |
| 98 | Minnesota Oncology Hematology, PA - Maplewood | Maplewood | Minnesota | United States | 55109 |
| 99 | Virginia Piper Cancer Institute at Abbott - Northwestern Hospital | Minneapolis | Minnesota | United States | 55407 |
| 100 | Hennepin County Medical Center - Minneapolis | Minneapolis | Minnesota | United States | 55415 |
| 101 | Humphrey Cancer Center at North Memorial Outpatient Center | Robbinsdale | Minnesota | United States | 55422-2900 |
| 102 | CCOP - Metro-Minnesota | Saint Louis Park | Minnesota | United States | 55416 |
| 103 | Park Nicollet Cancer Center | Saint Louis Park | Minnesota | United States | 55416 |
| 104 | Regions Hospital Cancer Care Center | Saint Paul | Minnesota | United States | 55101 |
| 105 | United Hospital | Saint Paul | Minnesota | United States | 55102 |
| 106 | Lakeview Hospital | Stillwater | Minnesota | United States | 55082 |
| 107 | Ridgeview Medical Center | Waconia | Minnesota | United States | 55387 |
| 108 | Willmar Cancer Center at Rice Memorial Hospital | Willmar | Minnesota | United States | 56201 |
| 109 | Minnesota Oncology Hematology, PA - Woodbury | Woodbury | Minnesota | United States | 55125 |
| 110 | Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis | Saint Louis | Missouri | United States | 63110 |
| 111 | CCOP - Montana Cancer Consortium | Billings | Montana | United States | 59101 |
| 112 | St. Vincent Healthcare Cancer Care Services | Billings | Montana | United States | 59101 |
| 113 | Hematology-Oncology Centers of the Northern Rockies - Billings | Billings | Montana | United States | 59102 |
| 114 | Billings Clinic - Downtown | Billings | Montana | United States | 59107-7000 |
| 115 | Bozeman Deaconess Cancer Center | Bozeman | Montana | United States | 59715 |
| 116 | St. James Healthcare Cancer Care | Butte | Montana | United States | 59701 |
| 117 | Big Sky Oncology | Great Falls | Montana | United States | 59405-5309 |
| 118 | Great Falls Clinic - Main Facility | Great Falls | Montana | United States | 59405 |
| 119 | Sletten Cancer Institute at Benefis Healthcare | Great Falls | Montana | United States | 59405 |
| 120 | St. Peter's Hospital | Helena | Montana | United States | 59601 |
| 121 | Glacier Oncology, PLLC | Kalispell | Montana | United States | 59901 |
| 122 | Kalispell Medical Oncology at KRMC | Kalispell | Montana | United States | 59901 |
| 123 | Kalispell Regional Medical Center | Kalispell | Montana | United States | 59901 |
| 124 | Montana Cancer Specialists at Montana Cancer Center | Missoula | Montana | United States | 59807-7877 |
| 125 | Montana Cancer Center at St. Patrick Hospital and Health Sciences Center | Missoula | Montana | United States | 59807 |
| 126 | Saint Francis Cancer Treatment Center at Saint Francis Memorial Health Center | Grand Island | Nebraska | United States | 68803 |
| 127 | Good Samaritan Cancer Center at Good Samaritan Hospital | Kearney | Nebraska | United States | 68848-1990 |
| 128 | Cancer Resource Center - Lincoln | Lincoln | Nebraska | United States | 68510 |
| 129 | Callahan Cancer Center at Great Plains Regional Medical Center | North Platte | Nebraska | United States | 69103 |
| 130 | CCOP - Missouri Valley Cancer Consortium | Omaha | Nebraska | United States | 68106 |
| 131 | Methodist Estabrook Cancer Center | Omaha | Nebraska | United States | 68114 |
| 132 | Immanuel Medical Center | Omaha | Nebraska | United States | 68122 |
| 133 | Alegant Health Cancer Center at Bergan Mercy Medical Center | Omaha | Nebraska | United States | 68124 |
| 134 | Lakeside Hospital | Omaha | Nebraska | United States | 68130 |
| 135 | Creighton University Medical Center | Omaha | Nebraska | United States | 68131-2197 |
| 136 | UNMC Eppley Cancer Center at the University of Nebraska Medical Center | Omaha | Nebraska | United States | 68198-6805 |
| 137 | University Medical Center of Southern Nevada | Las Vegas | Nevada | United States | 89102 |
| 138 | CCOP - Nevada Cancer Research Foundation | Las Vegas | Nevada | United States | 89106 |
| 139 | Nevada Cancer Institute | Las Vegas | Nevada | United States | 89135 |
| 140 | New Hampshire Oncology - Hematology, PA at Payson Center for Cancer Care | Concord | New Hampshire | United States | 03301 |
| 141 | Center for Cancer Care at Exeter Hospital | Exeter | New Hampshire | United States | 03833 |
| 142 | New Hampshire Oncology - Hematology, PA - Hooksett | Hooksett | New Hampshire | United States | 03106 |
| 143 | Dana-Farber Cancer Institute at Londonderry | Londonderry | New Hampshire | United States | 03053 |
| 144 | Elliot Regional Cancer Center at Elliot Hospital | Manchester | New Hampshire | United States | 03103 |
| 145 | Veterans Affairs Medical Center - East Orange | East Orange | New Jersey | United States | 07018-1095 |
| 146 | Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare | Vineland | New Jersey | United States | 08360 |
| 147 | Lovelace Medical Center - Downtown | Albuquerque | New Mexico | United States | 87102 |
| 148 | University of New Mexico Cancer Center | Albuquerque | New Mexico | United States | 87131-5636 |
| 149 | Kings County Hospital Center | Brooklyn | New York | United States | 11203 |
| 150 | SUNY Downstate Medical Center | Brooklyn | New York | United States | 11203 |
| 151 | Veterans Affairs Medical Center - Buffalo | Buffalo | New York | United States | 14215 |
| 152 | Roswell Park Cancer Institute | Buffalo | New York | United States | 14263-0001 |
| 153 | CCOP - Hematology-Oncology Associates of Central New York | East Syracuse | New York | United States | 13057 |
| 154 | New York Weill Cornell Cancer Center at Cornell University | New York | New York | United States | 10021 |
| 155 | SUNY Upstate Medical University Hospital | Syracuse | New York | United States | 13210 |
| 156 | Veterans Affairs Medical Center - Syracuse | Syracuse | New York | United States | 13210 |
| 157 | Duke Cancer Institute | Durham | North Carolina | United States | 27710 |
| 158 | Kinston Medical Specialists | Kinston | North Carolina | United States | 28501 |
| 159 | Southeastern Regional Medical Center | Lumberton | North Carolina | United States | 28359 |
| 160 | Granville Medical Center | Oxford | North Carolina | United States | 27565 |
| 161 | Duke Health Raleigh Hospital | Raleigh | North Carolina | United States | 27609 |
| 162 | Person Memorial Hospital | Roxboro | North Carolina | United States | 27573 |
| 163 | Wood County Oncology Center | Bowling Green | Ohio | United States | 43402 |
| 164 | MetroHealth Cancer Care Center at MetroHealth Medical Center | Cleveland | Ohio | United States | 44109 |
| 165 | Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center | Columbus | Ohio | United States | 43210-1240 |
| 166 | St. Rita's Medical Center | Lima | Ohio | United States | 45801 |
| 167 | Lima Memorial Hospital | Lima | Ohio | United States | 45804 |
| 168 | Northwest Ohio Oncology Center | Maumee | Ohio | United States | 43537-1839 |
| 169 | Fisher-Titus Medical Center | Norwalk | Ohio | United States | 44857 |
| 170 | St. Charles Mercy Hospital | Oregon | Ohio | United States | 43616 |
| 171 | Toledo Clinic - Oregon | Oregon | Ohio | United States | 43616 |
| 172 | North Coast Cancer Care, Incorporated | Sandusky | Ohio | United States | 44870 |
| 173 | Flower Hospital Cancer Center | Sylvania | Ohio | United States | 43560 |
| 174 | Mercy Hospital of Tiffin | Tiffin | Ohio | United States | 44883 |
| 175 | Toledo Hospital | Toledo | Ohio | United States | 43606 |
| 176 | St. Vincent Mercy Medical Center | Toledo | Ohio | United States | 43608 |
| 177 | Medical University of Ohio Cancer Center | Toledo | Ohio | United States | 43614 |
| 178 | CCOP - Toledo Community Hospital | Toledo | Ohio | United States | 43617 |
| 179 | St. Anne Mercy Hospital | Toledo | Ohio | United States | 43623 |
| 180 | Toledo Clinic, Incorporated - Main Clinic | Toledo | Ohio | United States | 43623 |
| 181 | Fulton County Health Center | Wauseon | Ohio | United States | 43567 |
| 182 | Oklahoma University Cancer Institute | Oklahoma City | Oklahoma | United States | 73104 |
| 183 | Bay Area Hospital | Coos Bay | Oregon | United States | 97420 |
| 184 | Kaiser Permanente Health Care - Portland | Portland | Oregon | United States | 97227 |
| 185 | Mercy Hospital Cancer Center - Scranton | Scranton | Pennsylvania | United States | 18501 |
| 186 | Susquehanna Cancer Center at Divine Providence Hospital | Williamsport | Pennsylvania | United States | 17701 |
| 187 | Greenville Hospital Cancer Center | Greenville | South Carolina | United States | 29605 |
| 188 | CCOP - Greenville | Greenville | South Carolina | United States | 29615 |
| 189 | Self Regional Cancer Center at Self Regional Medical Center | Greenwood | South Carolina | United States | 29646 |
| 190 | MBCCOP - Meharry Medical College - Nashville | Nashville | Tennessee | United States | 37208-3599 |
| 191 | Baylor University Medical Center - Houston | Houston | Texas | United States | 77030 |
| 192 | Ben Taub General Hospital | Houston | Texas | United States | 77030 |
| 193 | St. Luke's Texas Cancer Institute at St. Luke's Episcopal Hospital | Houston | Texas | United States | 77030 |
| 194 | Veterans Affairs Medical Center - Houston | Houston | Texas | United States | 77030 |
| 195 | American Fork Hospital | American Fork | Utah | United States | 84003 |
| 196 | Sandra L. Maxwell Cancer Center | Cedar City | Utah | United States | 84720 |
| 197 | Logan Regional Hospital | Logan | Utah | United States | 84321 |
| 198 | Jon and Karen Huntsman Cancer Center at Intermountain Medical Center | Murray | Utah | United States | 84157 |
| 199 | Val and Ann Browning Cancer Center at McKay-Dee Hospital Center | Ogden | Utah | United States | 84403 |
| 200 | Utah Valley Regional Medical Center - Provo | Provo | Utah | United States | 84604 |
| 201 | Dixie Regional Medical Center - East Campus | Saint George | Utah | United States | 84770 |
| 202 | Utah Cancer Specialists at UCS Cancer Center | Salt Lake City | Utah | United States | 84106 |
| 203 | Huntsman Cancer Institute at University of Utah | Salt Lake City | Utah | United States | 84112 |
| 204 | LDS Hospital | Salt Lake City | Utah | United States | 84143 |
| 205 | Mountainview Medical | Berlin | Vermont | United States | 05602 |
| 206 | Fletcher Allen Health Care - University Health Center Campus | Burlington | Vermont | United States | 05401 |
| 207 | Kaiser Permanente Medical Center - Fair Oaks | Fairfax | Virginia | United States | 22033 |
| 208 | Fredericksburg Oncology, Incorporated | Fredericksburg | Virginia | United States | 22401 |
| 209 | Lynchburg Hematology-Oncology Clinic | Lynchburg | Virginia | United States | 24501 |
| 210 | Island Hospital Cancer Care Center at Island Hospital | Anacortes | Washington | United States | 98221 |
| 211 | St. Joseph Cancer Center | Bellingham | Washington | United States | 98225 |
| 212 | Olympic Hematology and Oncology | Bremerton | Washington | United States | 98310 |
| 213 | Highline Medical Center Cancer Center | Burien | Washington | United States | 98166 |
| 214 | Columbia Basin Hematology | Kennewick | Washington | United States | 99336 |
| 215 | Skagit Valley Hospital Cancer Care Center | Mount Vernon | Washington | United States | 98274 |
| 216 | Minor and James Medical, PLLC | Seattle | Washington | United States | 98104 |
| 217 | Group Health Central Hospital | Seattle | Washington | United States | 98112 |
| 218 | Swedish Cancer Institute at Swedish Medical Center - First Hill Campus | Seattle | Washington | United States | 98122-4307 |
| 219 | University Cancer Center at University of Washington Medical Center | Seattle | Washington | United States | 98195 |
| 220 | North Puget Oncology at United General Hospital | Sedro-Woolley | Washington | United States | 98284 |
| 221 | Cancer Care Northwest - Spokane South | Spokane | Washington | United States | 99202 |
| 222 | Rockwood Clinic Cancer Treatment Center | Spokane | Washington | United States | 99204-2967 |
| 223 | Evergreen Hematology and Oncology, PS | Spokane | Washington | United States | 99218 |
| 224 | Wenatchee Valley Medical Center | Wenatchee | Washington | United States | 98801-2028 |
| 225 | Langlade Memorial Hospital | Antigo | Wisconsin | United States | 54409 |
| 226 | Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center | Green Bay | Wisconsin | United States | 54301-3526 |
| 227 | Green Bay Oncology, Limited at St. Mary's Hospital | Green Bay | Wisconsin | United States | 54303 |
| 228 | St. Mary's Hospital Medical Center - Green Bay | Green Bay | Wisconsin | United States | 54303 |
| 229 | St. Vincent Hospital Regional Cancer Center | Green Bay | Wisconsin | United States | 54307-3508 |
| 230 | Holy Family Memorial Medical Center Cancer Care Center | Manitowoc | Wisconsin | United States | 54221-1450 |
| 231 | Bay Area Cancer Care Center at Bay Area Medical Center | Marinette | Wisconsin | United States | 54143 |
| 232 | Wheaton Franciscan Cancer Care - St. Joseph | Milwaukee | Wisconsin | United States | 53210 |
| 233 | Green Bay Oncology, Limited - Oconto Falls | Oconto Falls | Wisconsin | United States | 54154 |
| 234 | St. Nicholas Hospital | Sheboygan | Wisconsin | United States | 53081 |
| 235 | Green Bay Oncology, Limited - Sturgeon Bay | Sturgeon Bay | Wisconsin | United States | 54235 |
| 236 | University of Wisconcin Cancer Center at Aspirus Wausau Hospital | Wausau | Wisconsin | United States | 54401 |
| 237 | Riverview UW Cancer Center at Riverview Hospital | Wisconsin Rapids | Wisconsin | United States | 54494 |
| 238 | Welch Cancer Center at Sheridan Memorial Hospital | Sheridan | Wyoming | United States | 82801 |
| 239 | Cross Cancer Institute at University of Alberta | Edmonton | Alberta | Canada | T6G 1Z2 |
| 240 | University of British Columbia | Vancouver | British Columbia | Canada | V5Z 3P1 |
| 241 | London Regional Cancer Program at London Health Sciences Centre | London | Ontario | Canada | N6A 4L6 |
Sponsors and Collaborators
- Alliance for Clinical Trials in Oncology
- National Cancer Institute (NCI)
- Southwest Oncology Group
- Eastern Cooperative Oncology Group
- NCIC Clinical Trials Group
- Novartis Pharmaceuticals
Investigators
- Study Chair: Matthew R. Smith, MD, PhD, Massachusetts General Hospital
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00079001
Other Study ID Numbers:
- CALGB-90202
- U10CA031946
- CAN-NCIC-PRC2
- CDR0000353209
- NCT00698308
First Posted:
Mar 9, 2004
Last Update Posted:
May 12, 2020
Last Verified:
Apr 1, 2020
Keywords provided by Alliance for Clinical Trials in Oncology
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Between January 2004 and May 2012, 645 participants were registered and randomized. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Zoledronic Acid + Androgen Deprivation Therapy | Placebo + Androgen Deprivation Therapy |
|---|---|---|
| Arm/Group Description | 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). | 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. |
| Period Title: Overall Study | ||
| STARTED | 323 | 322 |
| COMPLETED | 323 | 322 |
| NOT COMPLETED | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Zoledronic Acid + Androgen Deprivation Therapy | Placebo + Androgen Deprivation Therapy | Total |
|---|---|---|---|
| Arm/Group Description | 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). | 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. | Total of all reporting groups |
| Overall Participants | 323 | 322 | 645 |
| Age (years) [Median (Inter-Quartile Range) ] | |||
| Median (Inter-Quartile Range) [years] |
66.1
|
66.7
|
66.3
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
0
0%
|
0
0%
|
0
0%
|
| Male |
323
100%
|
322
100%
|
645
100%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
1
0.3%
|
1
0.3%
|
2
0.3%
|
| Asian |
7
2.2%
|
4
1.2%
|
11
1.7%
|
| Native Hawaiian or Other Pacific Islander |
2
0.6%
|
1
0.3%
|
3
0.5%
|
| Black or African American |
42
13%
|
50
15.5%
|
92
14.3%
|
| White |
261
80.8%
|
256
79.5%
|
517
80.2%
|
| More than one race |
0
0%
|
1
0.3%
|
1
0.2%
|
| Unknown or Not Reported |
10
3.1%
|
9
2.8%
|
19
2.9%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
323
100%
|
321
99.7%
|
644
99.8%
|
| Canada |
0
0%
|
1
0.3%
|
1
0.2%
|
| ECOG Performance Status (participants) [Number] | |||
| 0 |
205
63.5%
|
205
63.7%
|
410
63.6%
|
| 1 |
105
32.5%
|
105
32.6%
|
210
32.6%
|
| 2 |
13
4%
|
12
3.7%
|
25
3.9%
|
| Prior Skeletal Related Event (participants) [Number] | |||
| Yes |
42
13%
|
40
12.4%
|
82
12.7%
|
| No |
281
87%
|
282
87.6%
|
563
87.3%
|
Outcome Measures
| Title | Time to First Skeletal Related Event |
|---|---|
| Description | 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. |
| Time Frame | Up to 10 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Zoledronic Acid + Androgen Deprivation Therapy | Placebo + Androgen Deprivation Therapy |
|---|---|---|
| Arm/Group Description | 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). | 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. |
| Measure Participants | 323 | 322 |
| Median (95% Confidence Interval) [months] |
31.9
|
28.8
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Zoledronic Acid + Androgen Deprivation Therapy, Placebo + Androgen Deprivation Therapy |
|---|---|---|
| Comments | The null hypothesis was that the hazard ratio is greater than or equal to 1.0 versus the alternative hypothesis that the hazard ratio is less than 0.77. With a target of 470 SREs, log-rank statistic had 88% power to detect a 23% decrease in hazard of SRE (equivalent to an increase in median time to SRE from 30 months to 39 months), assuming a one-sided type I error rate of .05. | |
| Type of Statistical Test | Non-Inferiority or Equivalence (legacy) | |
| Comments | Superiority and futility analysis were conducted for time to first SRE. Lan-Demets analog of the Emerson-Fleming sequential boundary was used to maintain overall significance level of α = .05 while conducting interim analyses on time to first SRE. | |
| Statistical Test of Hypothesis | p-Value | 0.385 |
| Comments | Because of early termination, conditional power was performed under the alternative hypothesis. This is the probability that zoledronic acid is superior to placebo, given time to first SRE data at interim analysis under alternative hypothesis. | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.97 | |
| Confidence Interval |
(2-Sided) 95% 0 to 1.174 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Patients randomly assigned to zoledronic acid were compared with patients assigned to placebo | |
| Title | Overall Survival |
|---|---|
| Description | 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. |
| Time Frame | Up to 10 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Zoledronic Acid + Androgen Deprivation Therapy | Placebo + Androgen Deprivation Therapy |
|---|---|---|
| Arm/Group Description | 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). | 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. |
| Measure Participants | 323 | 322 |
| Median (95% Confidence Interval) [months] |
37.9
|
36.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Zoledronic Acid + Androgen Deprivation Therapy, Placebo + Androgen Deprivation Therapy |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.29 |
| Comments | ||
| Method | Log Rank | |
| Comments | Adjusted for stratification factors: performance status, prior SRE, and serum alkaline phosphatase. | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.88 | |
| Confidence Interval |
(2-Sided) 95% 0.70 to 1.12 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Zoledronic acid versus placebo group | |
| Title | Progression-free Survival |
|---|---|
| Description | 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. |
| Time Frame | Up to 10 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Zoledronic Acid + Androgen Deprivation Therapy | Placebo + Androgen Deprivation Therapy |
|---|---|---|
| Arm/Group Description | 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). | 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. |
| Measure Participants | 323 | 322 |
| Median (95% Confidence Interval) [months] |
10.6
|
9.2
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Zoledronic Acid + Androgen Deprivation Therapy, Placebo + Androgen Deprivation Therapy |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.22 |
| Comments | ||
| Method | Log Rank | |
| Comments | Adjusted for stratification factors: performance status, prior SRE, and serum alkaline phosphatase. | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.89 | |
| Confidence Interval |
(2-Sided) 95% 0.74 to 1.07 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Zoledronic acid versus placebo group | |
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table. | |||
| Arm/Group Title | Zoledronic Acid + Androgen Deprivation Therapy | Placebo + Androgen Deprivation Therapy | ||
| Arm/Group Description | 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). | 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. | ||
All Cause Mortality |
||||
| Zoledronic Acid + Androgen Deprivation Therapy | Placebo + Androgen Deprivation Therapy | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Zoledronic Acid + Androgen Deprivation Therapy | Placebo + Androgen Deprivation Therapy | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 60/310 (19.4%) | 61/308 (19.8%) | ||
| Blood and lymphatic system disorders | ||||
| Blood disorder | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Disseminated intravascular coagulation | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Hemoglobin decreased | 7/310 (2.3%) | 9 | 6/308 (1.9%) | 6 |
| Hemolysis | 0/310 (0%) | 0 | 3/308 (1%) | 3 |
| Cardiac disorders | ||||
| Arrhythmia supraventricular | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Atrial fibrillation | 0/310 (0%) | 0 | 2/308 (0.6%) | 2 |
| Cardiac disorder | 3/310 (1%) | 3 | 0/308 (0%) | 0 |
| Cardiac pain | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Left ventricular dysfunction | 0/310 (0%) | 0 | 2/308 (0.6%) | 5 |
| Myocardial ischemia | 5/310 (1.6%) | 5 | 2/308 (0.6%) | 2 |
| Sick sinus syndrome | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Sinus tachycardia | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Supraventricular tachycardia | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Endocrine disorders | ||||
| Endocrine disorder | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Hyperthyroidism | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Eye disorders | ||||
| Vision blurred | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Gastrointestinal disorders | ||||
| Abdominal distension | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Abdominal pain | 4/310 (1.3%) | 4 | 3/308 (1%) | 3 |
| Colitis | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Colonic obstruction | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Constipation | 1/310 (0.3%) | 1 | 3/308 (1%) | 3 |
| Diarrhea | 10/310 (3.2%) | 10 | 7/308 (2.3%) | 7 |
| Esophageal pain | 0/310 (0%) | 0 | 2/308 (0.6%) | 2 |
| Gastric hemorrhage | 0/310 (0%) | 0 | 2/308 (0.6%) | 2 |
| Gastric ulcer | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Intra-abdominal hemorrhage | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Lower gastrointestinal hemorrhage | 2/310 (0.6%) | 2 | 0/308 (0%) | 0 |
| Nausea | 14/310 (4.5%) | 14 | 18/308 (5.8%) | 21 |
| Rectal pain | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Small intestinal obstruction | 2/310 (0.6%) | 2 | 1/308 (0.3%) | 1 |
| Upper gastrointestinal hemorrhage | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Vomiting | 10/310 (3.2%) | 10 | 14/308 (4.5%) | 16 |
| General disorders | ||||
| Chest pain | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Chills | 5/310 (1.6%) | 5 | 2/308 (0.6%) | 2 |
| Death NOS | 1/310 (0.3%) | 1 | 1/308 (0.3%) | 1 |
| Disease progression | 3/310 (1%) | 3 | 3/308 (1%) | 3 |
| Edema limbs | 1/310 (0.3%) | 3 | 3/308 (1%) | 4 |
| Fatigue | 33/310 (10.6%) | 39 | 32/308 (10.4%) | 42 |
| Fever | 5/310 (1.6%) | 5 | 5/308 (1.6%) | 5 |
| General symptom | 0/310 (0%) | 0 | 2/308 (0.6%) | 2 |
| Pain | 3/310 (1%) | 3 | 2/308 (0.6%) | 2 |
| Sudden death | 3/310 (1%) | 3 | 1/308 (0.3%) | 1 |
| Infections and infestations | ||||
| Bladder infection | 2/310 (0.6%) | 3 | 2/308 (0.6%) | 3 |
| Catheter related infection | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Infection | 1/310 (0.3%) | 1 | 1/308 (0.3%) | 1 |
| Infectious colitis | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Pelvic infection | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Pneumonia | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Sepsis | 1/310 (0.3%) | 1 | 1/308 (0.3%) | 1 |
| Soft tissue infection | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Upper respiratory infection | 1/310 (0.3%) | 1 | 1/308 (0.3%) | 1 |
| Urethral infection | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Urinary tract infection | 4/310 (1.3%) | 4 | 3/308 (1%) | 4 |
| Injury, poisoning and procedural complications | ||||
| Fracture | 2/310 (0.6%) | 2 | 0/308 (0%) | 0 |
| Investigations | ||||
| Activated partial thromboplastin time prolonged | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Alanine aminotransferase increased | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Alkaline phosphatase increased | 3/310 (1%) | 3 | 2/308 (0.6%) | 2 |
| Aspartate aminotransferase increased | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| CD4 lymphocytes decreased | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Coagulopathy | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Creatinine increased | 22/310 (7.1%) | 25 | 18/308 (5.8%) | 19 |
| INR increased | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Laboratory test abnormal | 2/310 (0.6%) | 2 | 1/308 (0.3%) | 1 |
| Leukocyte count decreased | 2/310 (0.6%) | 2 | 2/308 (0.6%) | 2 |
| Lymphocyte count decreased | 3/310 (1%) | 3 | 1/308 (0.3%) | 1 |
| Neutrophil count decreased | 3/310 (1%) | 3 | 2/308 (0.6%) | 2 |
| Platelet count decreased | 1/310 (0.3%) | 1 | 2/308 (0.6%) | 2 |
| Weight loss | 0/310 (0%) | 0 | 2/308 (0.6%) | 3 |
| Metabolism and nutrition disorders | ||||
| Acidosis | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Anorexia | 16/310 (5.2%) | 18 | 18/308 (5.8%) | 21 |
| Blood bicarbonate decreased | 1/310 (0.3%) | 1 | 1/308 (0.3%) | 1 |
| Blood glucose increased | 1/310 (0.3%) | 1 | 3/308 (1%) | 3 |
| Blood uric acid increased | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Dehydration | 3/310 (1%) | 3 | 6/308 (1.9%) | 6 |
| Serum albumin decreased | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Serum calcium decreased | 18/310 (5.8%) | 21 | 18/308 (5.8%) | 21 |
| Serum glucose decreased | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Serum magnesium decreased | 0/310 (0%) | 0 | 6/308 (1.9%) | 7 |
| Serum magnesium increased | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Serum phosphate decreased | 10/310 (3.2%) | 11 | 8/308 (2.6%) | 8 |
| Serum potassium decreased | 16/310 (5.2%) | 16 | 9/308 (2.9%) | 10 |
| Serum potassium increased | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Serum sodium decreased | 4/310 (1.3%) | 4 | 1/308 (0.3%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 0/310 (0%) | 0 | 2/308 (0.6%) | 2 |
| Arthritis | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Back pain | 1/310 (0.3%) | 1 | 6/308 (1.9%) | 6 |
| Bone pain | 3/310 (1%) | 3 | 6/308 (1.9%) | 6 |
| Joint effusion | 0/310 (0%) | 0 | 2/308 (0.6%) | 3 |
| Muscle weakness | 3/310 (1%) | 3 | 1/308 (0.3%) | 1 |
| Muscle weakness lower limb | 1/310 (0.3%) | 1 | 2/308 (0.6%) | 2 |
| Musculoskeletal disorder | 4/310 (1.3%) | 4 | 0/308 (0%) | 0 |
| Myalgia | 13/310 (4.2%) | 18 | 22/308 (7.1%) | 27 |
| Neck pain | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Osteonecrosis | 3/310 (1%) | 4 | 0/308 (0%) | 0 |
| Pain in extremity | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Tumor pain | 0/310 (0%) | 0 | 2/308 (0.6%) | 2 |
| Tumor pain (onset or exacerbation of tumor pain due to treatment) | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Nervous system disorders | ||||
| Depressed level of consciousness | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Dizziness | 2/310 (0.6%) | 2 | 0/308 (0%) | 0 |
| Headache | 1/310 (0.3%) | 1 | 1/308 (0.3%) | 1 |
| Intracranial hemorrhage | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Ischemia cerebrovascular | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Memory impairment | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Neurological disorder NOS | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Oculomotor nerve disorder | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Peripheral motor neuropathy | 3/310 (1%) | 5 | 1/308 (0.3%) | 1 |
| Peripheral sensory neuropathy | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Syncope | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Syncope vasovagal | 2/310 (0.6%) | 2 | 0/308 (0%) | 0 |
| Psychiatric disorders | ||||
| Agitation | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Confusion | 1/310 (0.3%) | 1 | 2/308 (0.6%) | 2 |
| Depression | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Renal and urinary disorders | ||||
| Bladder hemorrhage | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Bladder obstruction | 0/310 (0%) | 0 | 2/308 (0.6%) | 2 |
| Cystitis | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Kidney pain | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Renal failure | 5/310 (1.6%) | 5 | 2/308 (0.6%) | 2 |
| Ureteric obstruction | 3/310 (1%) | 4 | 0/308 (0%) | 0 |
| Ureteric perforation | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Ureteric stenosis | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Urethral obstruction | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Urinary incontinence | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Urinary retention | 7/310 (2.3%) | 7 | 3/308 (1%) | 3 |
| Reproductive system and breast disorders | ||||
| Erectile dysfunction | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Pelvic pain | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Bronchial obstruction | 1/310 (0.3%) | 1 | 1/308 (0.3%) | 1 |
| Dyspnea | 3/310 (1%) | 4 | 5/308 (1.6%) | 7 |
| Hypoxia | 1/310 (0.3%) | 2 | 1/308 (0.3%) | 1 |
| Pleural effusion | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Pleuritic pain | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Pneumonitis | 0/310 (0%) | 0 | 3/308 (1%) | 3 |
| Pneumothorax | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Respiratory disorder | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||
| Pruritus | 4/310 (1.3%) | 4 | 1/308 (0.3%) | 1 |
| Rash desquamating | 3/310 (1%) | 3 | 4/308 (1.3%) | 4 |
| Vascular disorders | ||||
| Hypertension | 2/310 (0.6%) | 2 | 0/308 (0%) | 0 |
| Hypotension | 0/310 (0%) | 0 | 3/308 (1%) | 3 |
| Thrombosis | 1/310 (0.3%) | 1 | 4/308 (1.3%) | 4 |
| Vascular disorder | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| Zoledronic Acid + Androgen Deprivation Therapy | Placebo + Androgen Deprivation Therapy | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 269/310 (86.8%) | 266/308 (86.4%) | ||
| Blood and lymphatic system disorders | ||||
| Hemoglobin decreased | 8/310 (2.6%) | 14 | 6/308 (1.9%) | 6 |
| Hemolysis | 2/310 (0.6%) | 2 | 2/308 (0.6%) | 2 |
| Cardiac disorders | ||||
| Atrial fibrillation | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Atrial flutter | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Atrial tachycardia | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Cardiac disorder | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Cardiac valve disease | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Cardiopulmonary arrest | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Edema | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Left ventricular failure | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Myocardial ischemia | 1/310 (0.3%) | 1 | 1/308 (0.3%) | 1 |
| Palpitations | 0/310 (0%) | 0 | 2/308 (0.6%) | 2 |
| Sinus tachycardia | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Supraventricular tachycardia | 0/310 (0%) | 0 | 1/308 (0.3%) | 2 |
| Ear and labyrinth disorders | ||||
| Hearing impaired | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Tinnitus | 1/310 (0.3%) | 7 | 0/308 (0%) | 0 |
| Eye disorders | ||||
| Cataract | 3/310 (1%) | 3 | 2/308 (0.6%) | 3 |
| Retinal detachment | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Retinopathy | 0/310 (0%) | 0 | 1/308 (0.3%) | 10 |
| Vision blurred | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Gastrointestinal disorders | ||||
| Abdominal pain | 1/310 (0.3%) | 1 | 3/308 (1%) | 3 |
| Ascites | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Colonic obstruction | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Constipation | 5/310 (1.6%) | 6 | 6/308 (1.9%) | 6 |
| Diarrhea | 61/310 (19.7%) | 148 | 52/308 (16.9%) | 127 |
| Diarrhea patients with a colostomy | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Gastrointestinal disorder | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Jejunal obstruction | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Jejunal ulcer | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Nausea | 70/310 (22.6%) | 150 | 78/308 (25.3%) | 209 |
| Rectal pain | 1/310 (0.3%) | 1 | 1/308 (0.3%) | 2 |
| Salivary gland disorder | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Small intestinal obstruction | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Stomach pain | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Tooth disorder | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Vomiting | 40/310 (12.9%) | 59 | 41/308 (13.3%) | 67 |
| General disorders | ||||
| Chest pain | 1/310 (0.3%) | 1 | 2/308 (0.6%) | 2 |
| Chills | 37/310 (11.9%) | 64 | 25/308 (8.1%) | 55 |
| Disease progression | 3/310 (1%) | 3 | 1/308 (0.3%) | 1 |
| Fatigue | 191/310 (61.6%) | 1076 | 193/308 (62.7%) | 1232 |
| Fever | 43/310 (13.9%) | 56 | 29/308 (9.4%) | 42 |
| Gait abnormal | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Pain | 4/310 (1.3%) | 4 | 1/308 (0.3%) | 1 |
| Immune system disorders | ||||
| Hypersensitivity | 8/310 (2.6%) | 12 | 6/308 (1.9%) | 22 |
| Infections and infestations | ||||
| Bladder infection | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Catheter related infection | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Infection | 2/310 (0.6%) | 2 | 0/308 (0%) | 0 |
| Infection without neutropenia | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Infective myositis | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Otitis externa | 0/310 (0%) | 0 | 1/308 (0.3%) | 2 |
| Pneumonia | 2/310 (0.6%) | 2 | 1/308 (0.3%) | 1 |
| Skin infection | 3/310 (1%) | 3 | 1/308 (0.3%) | 1 |
| Tooth infection | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Urinary tract infection | 0/310 (0%) | 0 | 2/308 (0.6%) | 2 |
| Wound infection | 1/310 (0.3%) | 2 | 0/308 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||
| Fracture | 1/310 (0.3%) | 2 | 0/308 (0%) | 0 |
| Venous injury - Extremity-upper | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Investigations | ||||
| Alanine aminotransferase increased | 2/310 (0.6%) | 2 | 2/308 (0.6%) | 3 |
| Alkaline phosphatase increased | 16/310 (5.2%) | 25 | 13/308 (4.2%) | 21 |
| Aspartate aminotransferase increased | 0/310 (0%) | 0 | 2/308 (0.6%) | 2 |
| CD4 lymphocytes decreased | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Creatinine increased | 77/310 (24.8%) | 299 | 65/308 (21.1%) | 316 |
| Laboratory test abnormal | 3/310 (1%) | 6 | 1/308 (0.3%) | 1 |
| Leukocyte count decreased | 6/310 (1.9%) | 6 | 2/308 (0.6%) | 2 |
| Lipase increased | 0/310 (0%) | 0 | 1/308 (0.3%) | 2 |
| Lymphocyte count decreased | 2/310 (0.6%) | 8 | 2/308 (0.6%) | 5 |
| Neutrophil count decreased | 4/310 (1.3%) | 4 | 3/308 (1%) | 4 |
| Platelet count decreased | 1/310 (0.3%) | 2 | 2/308 (0.6%) | 4 |
| Weight gain | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Weight loss | 1/310 (0.3%) | 1 | 2/308 (0.6%) | 5 |
| Metabolism and nutrition disorders | ||||
| Anorexia | 54/310 (17.4%) | 128 | 58/308 (18.8%) | 128 |
| Blood bicarbonate decreased | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Blood glucose increased | 13/310 (4.2%) | 23 | 11/308 (3.6%) | 25 |
| Dehydration | 1/310 (0.3%) | 1 | 3/308 (1%) | 3 |
| Serum albumin decreased | 2/310 (0.6%) | 2 | 3/308 (1%) | 7 |
| Serum calcium decreased | 59/310 (19%) | 109 | 56/308 (18.2%) | 113 |
| Serum glucose decreased | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Serum magnesium decreased | 23/310 (7.4%) | 34 | 28/308 (9.1%) | 100 |
| Serum magnesium increased | 2/310 (0.6%) | 2 | 0/308 (0%) | 0 |
| Serum phosphate decreased | 38/310 (12.3%) | 101 | 38/308 (12.3%) | 79 |
| Serum potassium decreased | 44/310 (14.2%) | 108 | 36/308 (11.7%) | 89 |
| Serum potassium increased | 1/310 (0.3%) | 1 | 2/308 (0.6%) | 3 |
| Serum sodium decreased | 6/310 (1.9%) | 7 | 5/308 (1.6%) | 5 |
| Serum sodium increased | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 7/310 (2.3%) | 12 | 6/308 (1.9%) | 8 |
| Back pain | 14/310 (4.5%) | 32 | 8/308 (2.6%) | 11 |
| Bone pain | 20/310 (6.5%) | 32 | 21/308 (6.8%) | 30 |
| Joint disorder | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Muscle weakness | 4/310 (1.3%) | 8 | 0/308 (0%) | 0 |
| Muscle weakness lower limb | 0/310 (0%) | 0 | 1/308 (0.3%) | 11 |
| Musculoskeletal disorder | 2/310 (0.6%) | 2 | 0/308 (0%) | 0 |
| Myalgia | 166/310 (53.5%) | 849 | 140/308 (45.5%) | 680 |
| Neck pain | 1/310 (0.3%) | 6 | 1/308 (0.3%) | 1 |
| Osteonecrosis | 8/310 (2.6%) | 11 | 6/308 (1.9%) | 7 |
| Pain in extremity | 3/310 (1%) | 4 | 3/308 (1%) | 3 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Treatment related secondary malignancy | 3/310 (1%) | 3 | 0/308 (0%) | 0 |
| Tumor pain | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Nervous system disorders | ||||
| Depressed level of consciousness | 1/310 (0.3%) | 1 | 1/308 (0.3%) | 1 |
| Dizziness | 1/310 (0.3%) | 6 | 1/308 (0.3%) | 1 |
| Dysgeusia | 2/310 (0.6%) | 3 | 0/308 (0%) | 0 |
| Headache | 4/310 (1.3%) | 5 | 1/308 (0.3%) | 1 |
| Mini mental status examination abnormal | 1/310 (0.3%) | 17 | 0/308 (0%) | 0 |
| Neuralgia | 0/310 (0%) | 0 | 2/308 (0.6%) | 2 |
| Neurological disorder NOS | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Peripheral motor neuropathy | 1/310 (0.3%) | 1 | 2/308 (0.6%) | 2 |
| Peripheral sensory neuropathy | 0/310 (0%) | 0 | 1/308 (0.3%) | 2 |
| Seizure | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Syncope | 1/310 (0.3%) | 1 | 3/308 (1%) | 3 |
| Syncope vasovagal | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Psychiatric disorders | ||||
| Agitation | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Anxiety | 0/310 (0%) | 0 | 2/308 (0.6%) | 2 |
| Depression | 1/310 (0.3%) | 1 | 2/308 (0.6%) | 2 |
| Insomnia | 5/310 (1.6%) | 13 | 3/308 (1%) | 3 |
| Renal and urinary disorders | ||||
| Cystitis | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Hemorrhage urinary tract | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Kidney pain | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Kidney perforation | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Urinary frequency | 2/310 (0.6%) | 4 | 5/308 (1.6%) | 12 |
| Urinary retention | 3/310 (1%) | 6 | 4/308 (1.3%) | 7 |
| Urogenital disorder | 1/310 (0.3%) | 4 | 2/308 (0.6%) | 3 |
| Reproductive system and breast disorders | ||||
| Erectile dysfunction | 10/310 (3.2%) | 42 | 5/308 (1.6%) | 46 |
| Gynecomastia | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Pelvic pain | 1/310 (0.3%) | 3 | 1/308 (0.3%) | 1 |
| Prostatic obstruction | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Testicular pain | 2/310 (0.6%) | 2 | 0/308 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 3/310 (1%) | 5 | 5/308 (1.6%) | 5 |
| Dyspnea | 7/310 (2.3%) | 7 | 7/308 (2.3%) | 20 |
| Hypoxia | 1/310 (0.3%) | 1 | 3/308 (1%) | 12 |
| Pharyngeal stenosis | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Pneumonitis | 1/310 (0.3%) | 1 | 1/308 (0.3%) | 1 |
| Respiratory disorder | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 1/310 (0.3%) | 3 | 0/308 (0%) | 0 |
| Nail disorder | 0/310 (0%) | 0 | 1/308 (0.3%) | 1 |
| Pruritus | 22/310 (7.1%) | 70 | 25/308 (8.1%) | 79 |
| Rash desquamating | 36/310 (11.6%) | 74 | 47/308 (15.3%) | 120 |
| Skin disorder | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Vascular disorders | ||||
| Hemorrhage | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Hot flashes | 4/310 (1.3%) | 11 | 3/308 (1%) | 5 |
| Hypertension | 4/310 (1.3%) | 8 | 5/308 (1.6%) | 11 |
| Hypotension | 1/310 (0.3%) | 1 | 0/308 (0%) | 0 |
| Thrombosis | 1/310 (0.3%) | 1 | 3/308 (1%) | 3 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Must obtain prior Sponsor approval.
Results Point of Contact
| Name/Title | Matthew Smith, MD, PhD |
|---|---|
| Organization | Massachusetts General Hospital |
| Phone | |
| smith.matthew@mgh.harvard.edu |
Responsible Party:
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00079001
Other Study ID Numbers:
- CALGB-90202
- U10CA031946
- CAN-NCIC-PRC2
- CDR0000353209
- NCT00698308
First Posted:
Mar 9, 2004
Last Update Posted:
May 12, 2020
Last Verified:
Apr 1, 2020