Zoledronic Acid in Treating Patients With Metastatic Breast Cancer, Metastatic Prostate Cancer, or Multiple Myeloma With Bone Involvement

• Sponsor: Alliance for Clinical Trials in Oncology (Other)
• Overall Status: Completed
• CT.gov ID: NCT00869206
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 1,822
• Locations: 504
• Arms: 2
• Duration (Months): 94.1
• Patients Per Site: 3.6
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This randomized phase III trial studies two different schedules of zoledronic acid to compare how well they work in reducing bone-related complications in patients with breast cancer, prostate cancer, or multiple myeloma that has spread to other places in the body and have bone involvement. Bone-related complications are a major cause of morbidity in patients with metastatic prostate cancer, breast cancer, and multiple myeloma. Zoledronic acid may stop the growth of cancer cells in the bone and may help relieve some of the symptoms caused by bone metastases. It is not yet known whether giving zoledronic acid more or less frequently is more effective in treating patients with metastatic cancer that has spread to the bone.

Condition or Disease	Intervention/Treatment	Phase
Breast Adenocarcinoma; DS Stage I Plasma Cell Myeloma; DS Stage II Plasma Cell Myeloma; Metastatic Malignant Neoplasm to the Bone; Pain; Musculoskeletal Complication; Urinary Complications	Drug: zoledronic acid	Phase 3

Detailed Description

PRIMARY OBJECTIVES:

1. To determine whether every-12-week therapy with zoledronic acid is not inferior to every-4-week therapy for patients with metastatic breast cancer, metastatic prostate cancer, or multiple myeloma involving bone, as measured by the proportion who experience at least one skeletal related event within 24 months after randomization.

SECONDARY OBJECTIVES:

1. To compare pain scores (Brief Pain Inventory) of patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing.

2. To compare the functional status (Eastern Cooperative Oncology Group [ECOG] performance status) of patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing.

3. To compare the incidence of osteonecrosis of the jaw in patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing.

4. To compare the incidence of renal dysfunction in patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing.

5. To compare the skeletal morbidity rate of these patients, defined as the number of skeletal-related events per year, of patients receiving every 12 week dosing to those receiving every 4 week dosing.

6. To compare the suppression of serum markers of bone resorption of patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing.

7. To determine whether every 12 week therapy with zoledronic acid is not inferior to every-4-week therapy for each subgroup of patients with either breast cancer, prostate cancer, or multiple myeloma, as measured by the proportion who experience at least one skeletal related event within 24 months after randomization.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive zoledronic acid intravenously (IV) over at least 15 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive zoledronic acid IV over at least 15 minutes every 12 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 4 weeks for 2 years from registration.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1822 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: A Randomized, Phase III Study of Standard Dosing Versus Longer Dosing Interval of Zoledronic Acid in Metastatic Cancer
• Study Start Date: Mar 1, 2009
• Actual Primary Completion Date: Jun 1, 2014
• Actual Study Completion Date: Jan 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (zoledronic acid every 4 weeks) Patients receive zoledronic acid IV over at least 15 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.	Drug: zoledronic acid; Given IV
Experimental: Arm II (zoledronic acid every 12 weeks) Patients receive zoledronic acid IV over at least 15 minutes every 12 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.	Drug: zoledronic acid; Given IV

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With at Least One Skeletal-related Event (SRE) Within 2 Years After Randomization [2 years]

   To determine whether every-12-week therapy with zoledronic acid is not inferior to every-4-week therapy for patients with metastatic breast cancer, metastatic prostate cancer, or multiple myeloma involving bone, as measured by the proportion of patients who would have experienced at least one skeletal related event within 24 months after randomization.

Secondary Outcome Measures

1. Average Pain Intensity Score as Assessed by the Brief Pain Inventory (BPI) Questionnaire [from baseline up to 2 years]

   To compare pain scores (Brief Pain Inventory) of patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing. The change scores were evaluated in a general linear model with repeated measures for treatment effect and the time trend with patient-specific characteristics being adjusted for the mean interference score. Specifically the difference in score change per 4 weeks for Arm I using Arm II as the reference is reported. The score of the BPI questionnaire ranges from 0 being no pain to 10 being the most pain. The average score is reported for each arm below.

2. Average ECOG Performance Status [from baseline up to 2 years]

   To compare functional status (ECOG performance status) of patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing. The change scores were evaluated in a general linear model with repeated measures for treatment effect and the time trend with patient-specific characteristics being adjusted. Specifically the difference in score change per 4 weeks for Arm I using Arm II as the reference is reported. ECOG performance status is a measurement of a patients disability ranging from 0, fully active and able to carry out all pre disease performance without restriction, to 5, dead. The average performance status is reported below by arm.

3. Incidence of Osteonecrosis of the Jaw [from baseline up to 2 years]

   To compare the incidence of osteonecrosis of the jaw in patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing. The percentage of participants with osteonecrosis is reported here.

4. Incidence of Renal Dysfunction [from baseline up to 2 years]

   To compare the incidence of renal dysfunction of patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing. The percentage of patients with renal dysfunction, defined as grade 3 or grade 4 increased creatinine (Common Terminology Criteria for Adverse Events version 3.0), will be reported here.

5. Skeletal Morbidity Rate [from baseline up to 2 years]

   To compare the skeletal morbidity rate, defined as the number of skeletal-related events per year, of patients receiving every 12 week dosing to those receiving every 4 week dosing.

6. Bone Turnover Assessed by Serum C-telopeptide (CTX) Levels (Breast Cancer) [from baseline up to 2 years]

   To compare the suppression of serum markers of bone resorption of patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing. The number of patients with high & low CTX values by arm will be reported here.

7. Proportion of Patients Having at Least One SRE Within 24 Months After Randomization for the Subgroups of Patients With Breast Cancer [from baseline up to 24 months]

   To determine whether every 12 week therapy with zoledronic acid is not inferior to every-4-week therapy for patients with breast cancer, as measured by the proportion who experience at least one skeletal related event within 24 months after randomization.

8. Proportion of Patients Having at Least One SRE Within 24 Months After Randomization for the Subgroups of Patients With Prostate Cancer [from baseline up to 24 months]

   To determine whether every 12 week therapy with zoledronic acid is not inferior to every-4-week therapy for patients with prostate cancer, as measured by the proportion who experience at least one skeletal related event within 24 months after randomization.

9. Proportion of Patients Having at Least One SRE Within 24 Months After Randomization for the Subgroups of Patients With Multiple Myeloma [from baseline up to 24 months]

   To determine whether every 12 week therapy with zoledronic acid is not inferior to every-4-week therapy for patients with multiple myeloma, as measured by the proportion who experience at least one skeletal related event within 24 months after randomization.

10. Bone Turnover Assessed by Serum C-telopeptide (CTX) Levels (Prostate Cancer) [from baseline up to 24 months]

    To compare the suppression of serum markers of bone resorption of patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing. The number of patients with high & low CTX values by arm will be reported here.

11. Bone Turnover Assessed by Serum C-telopeptide (CTX) Levels (Multiple Myeloma) [from baseline up to 24 months]

    To compare the suppression of serum markers of bone resorption of patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing. The number of patients with high & low CTX values by arm will be reported here.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Eligibility Criteria:

• Histologic documentation of one of the following: breast adenocarcinoma, prostate adenocarcinoma or multiple myeloma

• At least one site of bone metastasis or bone involvement by radiologic imaging including plain radiograph, computed tomography (CT), positron emission tomography (PET) scan, PET/CT scan, magnetic resonance imaging, bone scan, or skeletal survey; indeterminate lesions should be confirmed by a second imaging method

• No prior treatment with IV bisphosphonates is allowed; prior treatment with oral bisphosphonates is allowed, but they must be discontinued prior to the initiation of protocol therapy

• No prior treatment with denosumab

• No prior treatment with radiopharmaceuticals; prior treatment with radioactive iodine is allowed; prostate cancer patients treated with brachytherapy are eligible

• Prior radiation therapy to bone is allowed, provided that at least one site of bone metastasis has not been irradiated and radiation is completed prior to registration; there should be no plan for radiation therapy to non-irradiated sites of bone metastases

• Prior adjuvant and metastatic chemotherapy, biologic therapy, and endocrine therapy is allowed

• No current treatment with investigational agent(s)

• Patients with known brain metastases are not eligible; patients who develop brain metastases during the study will be allowed to continue treatment as assigned

• Not pregnant and not nursing

• ECOG performance status 0-2

• 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) * Corrected serum calcium should be calculated using standard institutional practices

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fairbanks Cancer Treatment Center at Fairbanks Memorial Hospital	Fairbanks	Alaska	United States	99701
2	Mayo Clinic Scottsdale	Scottsdale	Arizona	United States	85259-5499
3	East Bay Radiation Oncology Center	Castro Valley	California	United States	94546
4	Valley Medical Oncology Consultants - Castro Valley	Castro Valley	California	United States	94546
5	North Bay Cancer Center	Fairfield	California	United States	94533
6	Valley Medical Oncology	Fremont	California	United States	94538
7	Rebecca and John Moores UCSD Cancer Center	La Jolla	California	United States	92093-0658
8	Contra Costa Regional Medical Center	Martinez	California	United States	94553-3156
9	Memorial Medical Center	Modesto	California	United States	95355
10	Camino Medical Group - Treatment Center	Mountain View	California	United States	94040
11	El Camino Hospital Cancer Center	Mountain View	California	United States	94040
12	Leavey Cancer Center at Northridge Hospital Medical Center	Northridge	California	United States	91328
13	Highland General Hospital	Oakland	California	United States	94602
14	Alta Bates Summit Medical Center - Summit Campus	Oakland	California	United States	94609
15	Bay Area Breast Surgeons, Incorporated	Oakland	California	United States	94609
16	CCOP - Bay Area Tumor Institute	Oakland	California	United States	94609
17	Larry G Strieff MD Medical Corporation	Oakland	California	United States	94609
18	Tom K Lee, Incorporated	Oakland	California	United States	94609
19	Palo Alto Medical Foundation	Palo Alto	California	United States	94301
20	Feather River Hospital Cancer Center	Paradise	California	United States	95969
21		Pismo Beach	California	United States	93449
22	Naval Medical Center - San Diego	San Diego	California	United States	92134
23	Veterans Affairs Medical Center - San Diego	San Diego	California	United States	92161
24	Doctors Medical Center - San Pablo Campus	San Pablo	California	United States	94806
25	Aurora Presbyterian Hospital	Aurora	Colorado	United States	80012
26	Boulder Community Hospital	Boulder	Colorado	United States	80301-9019
27	Memorial Hospital Cancer Center - Colorado Springs	Colorado Springs	Colorado	United States	80909
28	Penrose Cancer Center at Penrose Hospital	Colorado Springs	Colorado	United States	80933
29	St. Anthony Central Hospital	Denver	Colorado	United States	80204
30	Porter Adventist Hospital	Denver	Colorado	United States	80210
31	Presbyterian - St. Luke's Medical Center	Denver	Colorado	United States	80218
32	St. Joseph Hospital	Denver	Colorado	United States	80218
33	Rose Medical Center	Denver	Colorado	United States	80220
34	CCOP - Colorado Cancer Research Program	Denver	Colorado	United States	80224-2522
35	Swedish Medical Center	Englewood	Colorado	United States	80110
36	Poudre Valley Hospital	Fort Collins	Colorado	United States	80524
37	Front Range Cancer Specialists	Fort Collins	Colorado	United States	80528
38	St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center	Grand Junction	Colorado	United States	81502
39	North Colorado Medical Center	Greeley	Colorado	United States	80631
40	Littleton Adventist Hospital	Littleton	Colorado	United States	80122
41	Sky Ridge Medical Center	Lone Tree	Colorado	United States	80124
42	Hope Cancer Care Center at Longmont United Hospital	Longmont	Colorado	United States	80501
43	McKee Medical Center	Loveland	Colorado	United States	80539
44	Parker Adventist Hospital	Parker	Colorado	United States	80138
45	St. Mary - Corwin Regional Medical Center	Pueblo	Colorado	United States	81004
46	North Suburban Medical Center	Thornton	Colorado	United States	80229
47	Exempla Lutheran Medical Center	Wheat Ridge	Colorado	United States	80033
48	Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center	Hartford	Connecticut	United States	06105
49	Manchester Memorial Hospital	Manchester	Connecticut	United States	06040
50	Middlesex Hospital Cancer Center	Middletown	Connecticut	United States	06457
51	George Bray Cancer Center at the Hospital of Central Connecticut - New Britain Campus	New Britain	Connecticut	United States	06050
52	Tunnell Cancer Center at Beebe Medical Center	Lewes	Delaware	United States	19958
53	CCOP - Christiana Care Health Services	Newark	Delaware	United States	19713
54	Kaiser Permanente at Capitol Hill Medical Center	Washington	District of Columbia	United States	20002
55	Lombardi Comprehensive Cancer Center at Georgetown University Medical Center	Washington	District of Columbia	United States	20007
56	Sibley Memorial Hospital	Washington	District of Columbia	United States	20016
57	Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital	Fort Lauderdale	Florida	United States	33308
58	Broward General Medical Center Cancer Center	Fort Lauderdale	Florida	United States	33316
59	Mayo Clinic - Jacksonville	Jacksonville	Florida	United States	32224
60	Ella Milbank Foshay Cancer Center at Jupiter Medical Center	Jupiter	Florida	United States	33458
61	Cancer Center of South Florida Foundation, Incorporated	Lake Worth	Florida	United States	33461
62	CCOP - Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
63	Florida Hospital Cancer Institute at Florida Hospital Orlando	Orlando	Florida	United States	32803-1273
64	Cleveland Clinic Florida - Weston	Weston	Florida	United States	33331
65	Phoebe Cancer Center at Phoebe Putney Memorial Hospital	Albany	Georgia	United States	31701
66	Winship Cancer Institute of Emory University	Atlanta	Georgia	United States	30322
67	Veterans Affairs Medical Center - Atlanta (Decatur)	Decatur	Georgia	United States	30033
68	Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center	Savannah	Georgia	United States	31403-3089
69	Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler	Savannah	Georgia	United States	31405
70	Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center	Boise	Idaho	United States	83706
71	Mountain States Tumor Institute at St. Luke's Regional Medical Center	Boise	Idaho	United States	83712
72	St. Joseph Regional Medical Center	Lewiston	Idaho	United States	83501
73	John H. Stroger, Jr. Hospital of Cook County	Chicago	Illinois	United States	60612-3785
74	University of Illinois Cancer Center	Chicago	Illinois	United States	60612-7243
75	Veterans Affairs Medical Center - Chicago Westside Hospital	Chicago	Illinois	United States	60612
76	Louis A. Weiss Memorial Hospital	Chicago	Illinois	United States	60640
77	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois	United States	62526
78	Evanston Hospital	Evanston	Illinois	United States	60201-1781
79	Leonard C. Ferguson Cancer Center	Freeport	Illinois	United States	61032
80	Veterans Affairs Medical Center - Hines	Hines	Illinois	United States	60141
81	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois	United States	60435
82	La Grange Memorial Hospital	La Grange	Illinois	United States	60525
83	Trinity Cancer Center at Trinity Medical Center - 7th Street Campus	Moline	Illinois	United States	61265
84		Moline	Illinois	United States	61265
85	Hematology Oncology Consultants - Naperville	Naperville	Illinois	United States	60540
86	West Suburban Center for Cancer Care	River Forest	Illinois	United States	60305
87	Regional Cancer Center at Memorial Medical Center	Springfield	Illinois	United States	62781-0001
88	CCOP - Carle Cancer Center	Urbana	Illinois	United States	61801
89	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana	United States	46107
90	Elkhart Clinic, LLC	Elkhart	Indiana	United States	46514-2098
91	Michiana Hematology-Oncology, PC - Elkhart	Elkhart	Indiana	United States	46514
92	Elkhart General Hospital	Elkhart	Indiana	United States	46515
93	Howard Community Hospital	Kokomo	Indiana	United States	46904
94	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana	United States	46350
95	Clarian Arnett Cancer Care	Lafayette	Indiana	United States	47904
96	Suniti Medical Corporation	Merrillville	Indiana	United States	46410
97	Saint Anthony Memorial Health Centers	Michigan City	Indiana	United States	46360
98	Michiana Hematology-Oncology, PC - South Bend	Mishawaka	Indiana	United States	46545-1470
99	Saint Joseph Regional Medical Center	Mishawaka	Indiana	United States	46545-1470
100	Michiana Hematology Oncology PC - Plymouth	Plymouth	Indiana	United States	46563
101	Reid Hospital & Health Care Services	Richmond	Indiana	United States	47374
102	CCOP - Northern Indiana CR Consortium	South Bend	Indiana	United States	46601
103	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
104	Michiana Hematology Oncology PC - La Porte	Westville	Indiana	United States	46391
105	McFarland Clinic, PC	Ames	Iowa	United States	50010
106		Bettendorf	Iowa	United States	52722
107	Iowa Blood and Cancer Care	Cedar Rapids	Iowa	United States	52402
108	St. Luke's Hospital	Cedar Rapids	Iowa	United States	52402
109	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa	United States	52403
110	Mercy Regional Cancer Center at Mercy Medical Center	Cedar Rapids	Iowa	United States	52403
111	Medical Oncology and Hematology Associates - West Des Moines	Clive	Iowa	United States	50325
112	Genesis Regional Cancer Center at Genesis Medical Center	Davenport	Iowa	United States	52803
113	CCOP - Iowa Oncology Research Association	Des Moines	Iowa	United States	50309
114	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
115	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa	United States	50309
116	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa	United States	50314
117	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
118	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
119	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa	United States	52242-1002
120	Veterans Affairs Medical Center - Iowa City	Iowa City	Iowa	United States	52246
121	Mercy Cancer Center at Mercy Medical Center - North Iowa	Mason City	Iowa	United States	50401
122	McCreery Cancer Center at Ottumwa Regional	Ottumwa	Iowa	United States	52501
123	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa	United States	51101
124	Mercy Medical Center - Sioux City	Sioux City	Iowa	United States	51102
125	St. Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
126	Covenant Cancer Treatment Center	Waterloo	Iowa	United States	50702
127	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas	United States	66720
128	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas	United States	67801
129	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas	United States	67042
130	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas	United States	66701
131	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
132	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas	United States	67068
133	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
134	Cancer Center of Kansas, PA - Liberal	Liberal	Kansas	United States	67901
135	Cancer Center of Kansas, PA - Newton	Newton	Kansas	United States	67114
136	Menorah Medical Center	Overland Park	Kansas	United States	66209
137	Saint Luke's Hospital - South	Overland Park	Kansas	United States	66213
138	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas	United States	67357
139	CCOP - Kansas City	Prairie Village	Kansas	United States	66208
140	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas	United States	67124
141	Cancer Center of Kansas, PA - Salina	Salina	Kansas	United States	67401
142	Cotton-O'Neil Cancer Center	Topeka	Kansas	United States	66606
143	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas	United States	67152
144	Associates in Womens Health, PA - North Review	Wichita	Kansas	United States	67208
145	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas	United States	67208
146	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas	United States	67214
147	CCOP - Wichita	Wichita	Kansas	United States	67214
148	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
149	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas	United States	67156
150	Mary Bird Perkins Cancer Center - Baton Rouge	Baton Rouge	Louisiana	United States	70809
151	Ochsner Health Center - Bluebonnet	Baton Rouge	Louisiana	United States	70809
152	Ochsner Health Center - Covington	Covington	Louisiana	United States	70433
153	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana	United States	70112
154	Medical Center of Louisiana - New Orleans	New Orleans	Louisiana	United States	70112
155	CCOP - Ochsner	New Orleans	Louisiana	United States	70121
156	Ochsner Cancer Institute at Ochsner Clinic Foundation	New Orleans	Louisiana	United States	70121
157	Harold Alfond Center for Cancer Care	Augusta	Maine	United States	04330
158	CancerCare of Maine at Eastern Maine Medical Center	Bangor	Maine	United States	04401
159	Union Memorial Hospital	Baltimore	Maryland	United States	21218
160	Harry and Jeanette Weinberg Cancer Institute at Franklin Square Hospital Center	Baltimore	Maryland	United States	21237
161	Good Samaritan Hospital of Maryland	Baltimore	Maryland	United States	21239
162	Kaiser Permanente at Woodlawn Medical Center	Baltimore	Maryland	United States	21244
163	Shore Regional Cancer Center at Memorial Hospital - Easton	Easton	Maryland	United States	21601
164	Union Hospital of Cecil County	Elkton	Maryland	United States	21921
165	Kaiser Permanente - Gaithersburg Medical Center	Gaithersburg	Maryland	United States	20879
166	Kaiser Permanente Mid-Atlantic Medical Group-Largo Medical Facility	Largo	Maryland	United States	20774
167	Cancer Institute at St. Joseph Medical Center	Towson	Maryland	United States	21204
168	Sturdy Memorial Hospital	Attleboro	Massachusetts	United States	02703
169	Tufts Medical Center Cancer Center	Boston	Massachusetts	United States	02111
170	Caritas St. Elizabeth's Medical Center	Brighton	Massachusetts	United States	02135-2997
171	Addison Gilbert Hospital	Gloucester	Massachusetts	United States	01930
172	Caritas Holy Family Hospital	Methuen	Massachusetts	United States	01844
173	Jordan Hospital Club Cancer Center	Plymouth	Massachusetts	United States	02360
174	Commonwealth Hematology-Oncology, PC - Quincy	Quincy	Massachusetts	United States	02169
175	Baystate Regional Cancer Program at D'Amour Center for Cancer Care	Springfield	Massachusetts	United States	01199
176	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan	United States	49221
177	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan	United States	48106-0995
178	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan	United States	48106
179	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan	United States	48123-2500
180	Green Bay Oncology, Limited - Escanaba	Escanaba	Michigan	United States	49431
181	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
182	Hurley Medical Center	Flint	Michigan	United States	48503
183	Genesys Regional Medical Center	Grand Blanc	Michigan	United States	48439
184	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan	United States	48236
185	Dickinson County Healthcare System	Iron Mountain	Michigan	United States	49801
186	Foote Memorial Hospital	Jackson	Michigan	United States	49201
187	Borgess Medical Center	Kalamazoo	Michigan	United States	49001
188	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007-3731
189	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
190	Sparrow Regional Cancer Center	Lansing	Michigan	United States	48912-1811
191	St. Mary Mercy Hospital	Livonia	Michigan	United States	48154
192	Upper Michigan Cancer Center at Marquette General Hospital	Marquette	Michigan	United States	49855
193	Community Cancer Center of Monroe	Monroe	Michigan	United States	48162
194	Mercy Memorial Hospital - Monroe	Monroe	Michigan	United States	48162
195	Michiana Hematology Oncology PC - Niles	Niles	Michigan	United States	49120
196	St. Joseph Mercy Oakland	Pontiac	Michigan	United States	48341-2985
197	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan	United States	48060
198	William Beaumont Hospital - Royal Oak Campus	Royal Oak	Michigan	United States	48073
199	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan	United States	48601
200	Lakeland Regional Cancer Care Center - St. Joseph	Saint Joseph	Michigan	United States	49085
201	Lakeside Cancer Specialists, PLLC	Saint Joseph	Michigan	United States	49085
202	St. John Macomb Hospital	Warren	Michigan	United States	48093
203		Alexandria	Minnesota	United States	56308
204	MeritCare Bemidji	Bemidji	Minnesota	United States	56601
205	St. Joseph's Medical Center	Brainerd	Minnesota	United States	56401
206	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
207	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota	United States	55433
208	Duluth Clinic Cancer Center - Duluth	Duluth	Minnesota	United States	55805-1983
209	CCOP - Duluth	Duluth	Minnesota	United States	55805
210	Miller - Dwan Medical Center	Duluth	Minnesota	United States	55805
211	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
212	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota	United States	55432
213	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
214	Immanuel St. Joseph's	Mankato	Minnesota	United States	56002
215	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota	United States	55109
216	Minnesota Oncology - Maplewood	Maplewood	Minnesota	United States	55109
217	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota	United States	55407
218	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota	United States	55415
219	Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota	United States	55422-2900
220	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
221	CentraCare Clinic - River Campus	Saint Cloud	Minnesota	United States	56303
222	Coborn Cancer Center	Saint Cloud	Minnesota	United States	56303
223	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
224	Park Nicollet Cancer Center	Saint Louis Park	Minnesota	United States	55416
225	Regions Hospital Cancer Care Center	Saint Paul	Minnesota	United States	55101
226	United Hospital	Saint Paul	Minnesota	United States	55102
227	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota	United States	55379
228	Lakeview Hospital	Stillwater	Minnesota	United States	55082
229	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
230	Willmar Cancer Center at Rice Memorial Hospital	Willmar	Minnesota	United States	56201
231	Minnesota Oncology - Woodbury	Woodbury	Minnesota	United States	55125
232	Memorial Hospital at Gulfport	Gulfport	Mississippi	United States	39502
233	Veterans Affairs Medical Center - Jackson	Jackson	Mississippi	United States	39216
234	Keesler Air Force Base Medical Center	Keesler Air Force Base	Mississippi	United States	39534
235	Regional Cancer Center at Singing River Hospital	Pascagoula	Mississippi	United States	39581
236	Central Care Cancer Center at Carrie J. Babb Cancer Center	Bolivar	Missouri	United States	65613
237	Skaggs Cancer Center at Skaggs Regional Medical Center	Branson	Missouri	United States	65616
238	Southeast Cancer Center	Cape Girardeau	Missouri	United States	63703
239	Saint Luke's Hospital	Chesterfield	Missouri	United States	63017
240	Ellis Fischel Cancer Center at University of Missouri - Columbia	Columbia	Missouri	United States	65203
241	Goldschmidt Cancer Center	Jefferson City	Missouri	United States	65109
242	Saint Luke's Cancer Institute at Saint Luke's Hospital	Kansas City	Missouri	United States	64111
243	North Kansas City Hospital	Kansas City	Missouri	United States	64116
244	Parvin Radiation Oncology	Kansas City	Missouri	United States	64116
245	Heartland Hematology Oncology Associates, Incorporated	Kansas City	Missouri	United States	64118
246	Research Medical Center	Kansas City	Missouri	United States	64132
247	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri	United States	64086
248	Phelps County Regional Medical Center	Rolla	Missouri	United States	65401
249	Heartland Regional Medical Center	Saint Joseph	Missouri	United States	64506
250	Saint Joseph Oncology, Incorporated	Saint Joseph	Missouri	United States	64507
251	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	Saint Louis	Missouri	United States	63110
252	Missouri Baptist Cancer Center	Saint Louis	Missouri	United States	63131
253	Comprehensive Cancer Care, PC	Saint Louis	Missouri	United States	63141
254	CCOP - Cancer Research for the Ozarks	Springfield	Missouri	United States	65802
255	St. John's Regional Health Center	Springfield	Missouri	United States	65804
256	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri	United States	65807
257	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
258	St. Vincent Healthcare Cancer Care Services	Billings	Montana	United States	59101
259	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana	United States	59102
260	Billings Clinic - Downtown	Billings	Montana	United States	59107-7000
261	Bozeman Deaconess Cancer Center	Bozeman	Montana	United States	59715
262	St. James Healthcare Cancer Care	Butte	Montana	United States	59701
263	Great Falls Clinic - Main Facility	Great Falls	Montana	United States	59405
264	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana	United States	59405
265	Northern Montana Hospital	Havre	Montana	United States	59501
266	St. Peter's Hospital	Helena	Montana	United States	59601
267	Glacier Oncology, PLLC	Kalispell	Montana	United States	59901
268	Kalispell Medical Oncology at KRMC	Kalispell	Montana	United States	59901
269	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
270	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana	United States	59807-7877
271	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana	United States	59807
272	Saint Francis Cancer Treatment Center at Saint Francis Memorial Health Center	Grand Island	Nebraska	United States	68803
273	Good Samaritan Cancer Center at Good Samaritan Hospital	Kearney	Nebraska	United States	68848-1990
274	Cancer Resource Center - Lincoln	Lincoln	Nebraska	United States	68510
275	Callahan Cancer Center at Great Plains Regional Medical Center	North Platte	Nebraska	United States	69103
276	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska	United States	68106
277	Immanuel Medical Center	Omaha	Nebraska	United States	68122
278	Alegant Health Cancer Center at Bergan Mercy Medical Center	Omaha	Nebraska	United States	68124
279	Lakeside Hospital	Omaha	Nebraska	United States	68130
280	Creighton University Medical Center	Omaha	Nebraska	United States	68131-2197
281	UNMC Eppley Cancer Center at the University of Nebraska Medical Center	Omaha	Nebraska	United States	68198-6805
282	University Medical Center of Southern Nevada	Las Vegas	Nevada	United States	89102
283	CCOP - Nevada Cancer Research Foundation	Las Vegas	Nevada	United States	89106
284	Renown Institute for Cancer at Renown Regional Medical Center	Reno	Nevada	United States	89502
285	Saint Mary's Regional Medical Center	Reno	Nevada	United States	89503
286	Radiation Oncology Associates - Reno	Reno	Nevada	United States	89509
287	New Hampshire Oncology - Hematology, PA at Payson Center for Cancer Care	Concord	New Hampshire	United States	03301
288	Seacoast Cancer Center at Wentworth - Douglass Hospital	Dover	New Hampshire	United States	03820
289	Center for Cancer Care at Exeter Hospital	Exeter	New Hampshire	United States	03833
290	New Hampshire Oncology - Hematology, PA - Hooksett	Hooksett	New Hampshire	United States	03106
291	Lakes Region General Hospital	Laconia	New Hampshire	United States	03246
292	Foundation Medical Partners	Nashua	New Hampshire	United States	03060
293	Trinitas Comprehensive Cancer Center at Trinitas Hospital	Elizabeth	New Jersey	United States	07207
294	Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton	Marlton	New Jersey	United States	08053
295	Jersey Shore Cancer Center at Jersey Shore University Medical Center	Neptune	New Jersey	United States	07753
296	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey	United States	08043
297	Fox Chase Virtua Health Cancer Program at Virtua West Jersey	Voorhees	New Jersey	United States	08043
298	Lovelace Medical Center - Downtown	Albuquerque	New Mexico	United States	87102
299	Hematology Oncology Associates, PC	Albuquerque	New Mexico	United States	87106
300	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87131-5636
301	Lincoln Medical and Mental Health Center	Bronx	New York	United States	10451
302	Kings County Hospital Center	Brooklyn	New York	United States	11203
303	SUNY Downstate Medical Center	Brooklyn	New York	United States	11203
304	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001
305	Bassett Healthcare Regional Cancer Program at Mary Imogene Bassett Hospital	Cooperstown	New York	United States	13326
306	CCOP - Hematology-Oncology Associates of Central New York	East Syracuse	New York	United States	13057
307	Elmhurst Hospital Center	Elmhurst	New York	United States	11373
308	Charles R. Wood Cancer Center at Glens Falls Hospital	Glens Falls	New York	United States	12801
309	Queens Cancer Center of Queens Hospital	Jamaica	New York	United States	11432
310	Monter Cancer Center of the North Shore-LIJ Health System	Lake Success	New York	United States	11042
311	CCOP - North Shore University Hospital	Manhasset	New York	United States	11030
312	Don Monti Comprehensive Cancer Center at North Shore University Hospital	Manhasset	New York	United States	11030
313	Long Island Jewish Medical Center	New Hyde Park	New York	United States	11040
314	NYU Cancer Institute at New York University Medical Center	New York	New York	United States	10016
315	New York Weill Cornell Cancer Center at Cornell University	New York	New York	United States	10021
316	Nalitt Cancer Institute at Staten Island University Hospital	Staten Island	New York	United States	10305
317	Veterans Affairs Medical Center - Syracuse	Syracuse	New York	United States	13210
318	Dickstein Cancer Treatment Center at White Plains Hospital Center	White Plains	New York	United States	10601
319	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina	United States	27534
320	Leo W. Jenkins Cancer Center at ECU Medical School	Greenville	North Carolina	United States	27834
321	Pardee Memorial Hospital	Hendersonville	North Carolina	United States	28791
322	Kinston Medical Specialists	Kinston	North Carolina	United States	28501
323	FirstHealth Moore Regional Community Hospital Comprehensive Cancer Center	Pinehurst	North Carolina	United States	28374
324	Rutherford Hospital	Rutherfordton	North Carolina	United States	28139
325	Iredell Memorial Hospital	Statesville	North Carolina	United States	28677
326	Zimmer Cancer Center at New Hanover Regional Medical Center	Wilmington	North Carolina	United States	28401
327	Forsyth Regional Cancer Center at Forsyth Medical Center	Winston-Salem	North Carolina	United States	27103
328	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina	United States	27157-1096
329	Bismarck Cancer Center	Bismarck	North Dakota	United States	58501
330	Medcenter One Hospital Cancer Care Center	Bismarck	North Dakota	United States	58501
331	Mid Dakota Clinic, PC	Bismarck	North Dakota	United States	58501
332	St. Alexius Medical Center Cancer Center	Bismarck	North Dakota	United States	58502
333	MeritCare Broadway	Fargo	North Dakota	United States	58102
334	CCOP - MeritCare Hospital	Fargo	North Dakota	United States	58122
335	Roger Maris Cancer Center at MeritCare Hospital	Fargo	North Dakota	United States	58122
336	Altru Cancer Center at Altru Hospital	Grand Forks	North Dakota	United States	58201
337	Trinity CancerCare Center	Minot	North Dakota	United States	58701
338	McDowell Cancer Center at Akron General Medical Center	Akron	Ohio	United States	44307
339	Wood County Oncology Center	Bowling Green	Ohio	United States	43402
340	Aultman Cancer Center at Aultman Hospital	Canton	Ohio	United States	44710-1799
341	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
342	MetroHealth Cancer Care Center at MetroHealth Medical Center	Cleveland	Ohio	United States	44109
343	Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210-1240
344	Riverside Methodist Hospital Cancer Care	Columbus	Ohio	United States	43214-3998
345	CCOP - Columbus	Columbus	Ohio	United States	43215
346	Grant Medical Center Cancer Care	Columbus	Ohio	United States	43215
347	Mount Carmel Health - West Hospital	Columbus	Ohio	United States	43222
348	Doctors Hospital at Ohio Health	Columbus	Ohio	United States	43228
349	Grandview Hospital	Dayton	Ohio	United States	45405
350	Good Samaritan Hospital	Dayton	Ohio	United States	45406
351	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio	United States	45409
352	Samaritan North Cancer Care Center	Dayton	Ohio	United States	45415
353	CCOP - Dayton	Dayton	Ohio	United States	45420
354	Grady Memorial Hospital	Delaware	Ohio	United States	43015
355	Community Cancer Center	Elyria	Ohio	United States	44035
356	Hematology Oncology Center	Elyria	Ohio	United States	44035
357	Blanchard Valley Medical Associates	Findlay	Ohio	United States	45840
358	Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
359	Wayne Hospital	Greenville	Ohio	United States	45331
360	Charles F. Kettering Memorial Hospital	Kettering	Ohio	United States	45429
361	Fairfield Medical Center	Lancaster	Ohio	United States	43130
362	St. Rita's Medical Center	Lima	Ohio	United States	45801
363	Lima Memorial Hospital	Lima	Ohio	United States	45804
364	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio	United States	45750
365	Northwest Ohio Oncology Center	Maumee	Ohio	United States	43537-1839
366	Knox Community Hospital	Mount Vernon	Ohio	United States	43050
367	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio	United States	43055
368	Fisher-Titus Medical Center	Norwalk	Ohio	United States	44857
369	St. Charles Mercy Hospital	Oregon	Ohio	United States	43616
370	Toledo Clinic - Oregon	Oregon	Ohio	United States	43616
371	Southern Ohio Medical Center Cancer Center	Portsmouth	Ohio	United States	45662
372	North Coast Cancer Care, Incorporated	Sandusky	Ohio	United States	44870
373	Community Hospital of Springfield and Clark County	Springfield	Ohio	United States	45505
374	Flower Hospital Cancer Center	Sylvania	Ohio	United States	43560
375	Mercy Hospital of Tiffin	Tiffin	Ohio	United States	44883
376	Toledo Hospital	Toledo	Ohio	United States	43606
377	St. Vincent Mercy Medical Center	Toledo	Ohio	United States	43608
378	Medical University of Ohio Cancer Center	Toledo	Ohio	United States	43614
379	CCOP - Toledo Community Hospital	Toledo	Ohio	United States	43617
380	St. Anne Mercy Hospital	Toledo	Ohio	United States	43623
381	Toledo Clinic, Incorporated - Main Clinic	Toledo	Ohio	United States	43623
382	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio	United States	45373-1300
383	Fulton County Health Center	Wauseon	Ohio	United States	43567
384	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio	United States	43081
385	United States Air Force Medical Center - Wright-Patterson	Wright-Patterson Air Force Base	Ohio	United States	45433-5529
386	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio	United States	45385
387	Genesis - Good Samaritan Hospital	Zanesville	Ohio	United States	43701
388	LaFortune Cancer Center at St. John Medical Center	Tulsa	Oklahoma	United States	74104
389	Natalie Warren Bryant Cancer Center at St. Francis Hospital	Tulsa	Oklahoma	United States	74136
390	Clackamas Radiation Oncology Center	Clackamas	Oregon	United States	97015
391	Three Rivers Community Hospital	Grants Pass	Oregon	United States	97527
392	Dubs Cancer Center at Rogue Valley Medical Center	Medford	Oregon	United States	97504
393	Providence Cancer Center at PMCC	Medford	Oregon	United States	97504
394	Providence Milwaukie Hospital	Milwaukie	Oregon	United States	97222
395	Providence Newberg Medical Center	Newberg	Oregon	United States	97132
396	Willamette Falls Hospital	Oregon City	Oregon	United States	97045
397	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon	United States	97213-2967
398	CCOP - Columbia River Oncology Program	Portland	Oregon	United States	97225
399	Providence St. Vincent Medical Center	Portland	Oregon	United States	97225
400	Kaiser Permanente Health Care - Portland	Portland	Oregon	United States	97227
401	Salem Hospital Regional Cancer Care Services	Salem	Oregon	United States	97309-5014
402	Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest	Allentown	Pennsylvania	United States	18105
403	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania	United States	18017
404	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania	United States	19010
405	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania	United States	17822-0001
406	Doylestown Hospital Cancer Center	Doylestown	Pennsylvania	United States	18901
407	Delaware County Regional Cancer Center at Delaware County Memorial Hospital	Drexel Hill	Pennsylvania	United States	19026
408	Dale and Frances Hughes Cancer Center at Pocono Medical Center	East Stroudsburg	Pennsylvania	United States	18301
409	Easton Regional Cancer Center at Easton Hospital	Easton	Pennsylvania	United States	18042
410	Geisinger Hazleton Cancer Center	Hazleton	Pennsylvania	United States	18201
411	Lancaster General Hospital	Lancaster	Pennsylvania	United States	17604
412	St. Mary Regional Cancer Center	Langhorne	Pennsylvania	United States	19047
413	Riddle Memorial Hospital Cancer Center	Media	Pennsylvania	United States	19063
414	Cancer Center of Paoli Memorial Hospital	Paoli	Pennsylvania	United States	19301-1792
415	Joan Karnell Cancer Center at Pennsylvania Hospital	Philadelphia	Pennsylvania	United States	19107
416	Albert Einstein Cancer Center	Philadelphia	Pennsylvania	United States	19141
417	Cancer Center at Phoenixville Hospital	Phoenixville	Pennsylvania	United States	19460
418	Veterans Affairs Medical Center - Pittsburgh	Pittsburgh	Pennsylvania	United States	15240
419	Mercy Hospital Cancer Center - Scranton	Scranton	Pennsylvania	United States	18501
420	Hematology and Oncology Associates of Northeastern Pennsylvania	Scranton	Pennsylvania	United States	18510
421	Geisinger Medical Group - Scenery Park	State College	Pennsylvania	United States	16801
422	Chester County Hospital	West Chester	Pennsylvania	United States	19380
423	Jennersville Regional Hospital	West Grove	Pennsylvania	United States	19390-9499
424	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania	United States	18711
425	CCOP - Main Line Health	Wynnewood	Pennsylvania	United States	19096
426	Lankenau Cancer Center at Lankenau Hospital	Wynnewood	Pennsylvania	United States	19096
427	Rhode Island Hospital Comprehensive Cancer Center	Providence	Rhode Island	United States	02903
428	Miriam Hospital	Providence	Rhode Island	United States	02906
429	Roger Williams Medical Center	Providence	Rhode Island	United States	02908
430	AnMed Cancer Center	Anderson	South Carolina	United States	29621
431	Roper St. Francis Cancer Center at Roper Hospital	Charleston	South Carolina	United States	29401
432	McLeod Regional Medical Center	Florence	South Carolina	United States	29501
433	Carolina Blood and Cancer Care Associates, PA	Lancaster	South Carolina	United States	29720
434	Carolina Blood and Cancer Care	Rock Hill	South Carolina	United States	29732
435	CCOP - Upstate Carolina	Spartanburg	South Carolina	United States	29303
436	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina	United States	29303
437	Lexington Medical Center	West Columbia	South Carolina	United States	29169
438	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
439	Medical X-Ray Center, PC	Sioux Falls	South Dakota	United States	57105
440	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota	United States	57117-5039
441	Thompson Cancer Survival Center	Knoxville	Tennessee	United States	37916
442	Martha Jefferson Hospital Cancer Care Center	Charlottesville	Virginia	United States	22901
443	Medical Oncology and Hematology Associates of North Virginia - Fairfax	Fairfax	Virginia	United States	22031
444	Kaiser Permanente Medical Center - Fair Oaks	Fairfax	Virginia	United States	22033
445	Fredericksburg Oncology, Incorporated	Fredericksburg	Virginia	United States	22401
446	Veterans Affairs Medical Center - Richmond	Richmond	Virginia	United States	23249
447	Virginia Commonwealth University Massey Cancer Center	Richmond	Virginia	United States	23298-0037
448	Overlake Cancer Center at Overlake Hospital Medical Center	Bellevue	Washington	United States	98004
449	Providence Centralia Hospital	Centralia	Washington	United States	98531-9027
450	Providence Regional Cancer Partnership	Everett	Washington	United States	98201
451	St. Francis Hospital	Federal Way	Washington	United States	98003
452	Cascade Cancer Center at Evergreen Hospital Medical Center	Kirkland	Washington	United States	98033
453	Providence St. Peter Hospital Regional Cancer Center	Olympia	Washington	United States	98506-5166
454	Good Samaritan Cancer Center	Puyallup	Washington	United States	98372
455	CCOP - Virginia Mason Research Center	Seattle	Washington	United States	98101
456	Virginia Mason Medical Center	Seattle	Washington	United States	98101
457	Pacific Medical Center	Seattle	Washington	United States	98104
458	Franciscan Cancer Center at St. Joseph Medical Center	Tacoma	Washington	United States	98405-3004
459	Allenmore Hospital	Tacoma	Washington	United States	98405
460	CCOP - Northwest	Tacoma	Washington	United States	98405
461	MultiCare Regional Cancer Center at Tacoma General Hospital	Tacoma	Washington	United States	98405
462	St. Clare Hospital	Tacoma	Washington	United States	98499
463	Southwest Washington Medical Center Cancer Center	Vancouver	Washington	United States	98664
464	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington	United States	98902
465	St. Mary's Regional Cancer Center at St. Mary's Medical Center	Huntington	West Virginia	United States	25702
466	Langlade Memorial Hospital	Antigo	Wisconsin	United States	54409
467	Marshfield Clinic - Chippewa Center	Chippewa Falls	Wisconsin	United States	54729
468	Marshfield Clinic Cancer Care at Regional Cancer Center	Eau Claire	Wisconsin	United States	54701
469	Midelfort Clinic - Luther	Eau Claire	Wisconsin	United States	54703-1510
470	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54301-3526
471	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin	United States	54303
472	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin	United States	54303
473	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54307-3508
474	Vince Lombardi Cancer Clinic - Green Bay at Aurora BayCare Medical Center	Green Bay	Wisconsin	United States	54311
475	Mercy Regional Cancer Center	Janesville	Wisconsin	United States	53547
476	Franciscan Skemp Healthcare - La Crosse Campus	La Crosse	Wisconsin	United States	54601
477	Gundersen Lutheran Center for Cancer and Blood	La Crosse	Wisconsin	United States	54601
478	Holy Family Memorial Medical Center Cancer Care Center	Manitowoc	Wisconsin	United States	54221-1450
479	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin	United States	54143
480	Vince Lombardi Cancer Clinic - Marinette	Marinette	Wisconsin	United States	54143
481	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin	United States	54449
482	Columbia Saint Mary's Hospital - Ozaukee	Mequon	Wisconsin	United States	53097
483	Columbia-Saint Mary's Cancer Care Center	Milwaukee	Wisconsin	United States	53211
484	Marshfield Clinic - Lakeland Center	Minocqua	Wisconsin	United States	54548
485	D.N. Greenwald Center	Mukwonago	Wisconsin	United States	53149
486	Regional Cancer Center at Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin	United States	53066
487	Green Bay Oncology, Limited - Oconto Falls	Oconto Falls	Wisconsin	United States	54154
488	All Saints Cancer Center at Wheaton Franciscan Healthcare	Racine	Wisconsin	United States	53405
489	Ministry Medical Group at Saint Mary's Hospital	Rhinelander	Wisconsin	United States	54501
490	Marshfield Clinic - Indianhead Center	Rice Lake	Wisconsin	United States	54868
491	St. Nicholas Hospital	Sheboygan	Wisconsin	United States	53081
492	Vince Lombardi Cancer Clinic - Sheboygan	Sheboygan	Wisconsin	United States	53081
493	Marshfield Clinic at Saint Michael's Hospital	Stevens Point	Wisconsin	United States	54481
494	Green Bay Oncology, Limited - Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235
495	Aurora Medical Center	Summit	Wisconsin	United States	53066
496	Vince Lombardi Cancer Clinic - Two Rivers	Two Rivers	Wisconsin	United States	54241
497	Waukesha Memorial Hospital Regional Cancer Center	Waukesha	Wisconsin	United States	53188
498	University of Wisconcin Cancer Center at Aspirus Wausau Hospital	Wausau	Wisconsin	United States	54401
499	Oncology Alliance, SC - Milwaukee - West	Wauwatosa	Wisconsin	United States	53226
500	Marshfield Clinic - Weston Center	Weston	Wisconsin	United States	54476
501	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin	United States	54494
502	Riverview UW Cancer Center at Riverview Hospital	Wisconsin Rapids	Wisconsin	United States	54494
503	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming	United States	82801
504	San Juan City Hospital	San Juan		Puerto Rico	00936

Sponsors and Collaborators

• Alliance for Clinical Trials in Oncology
• National Cancer Institute (NCI)

Investigators

• Study Chair: Andrew L. Himelstein, MD, Helen F. Graham Cancer Center at Christiana Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alliance for Clinical Trials in Oncology
• ClinicalTrials.gov Identifier: NCT00869206
• Other Study ID Numbers: CALGB-70604; CDR0000637947; NCI-2009-01102; U10CA037447
• First Posted: Mar 25, 2009
• Last Update Posted: Nov 7, 2018
• Last Verified: Oct 1, 2018

• Keywords provided by Alliance for Clinical Trials in Oncology: pain; Prostate Adenocarcinoma; urinary complications; stage IV breast cancer; Recurrent Breast Carcinoma; stage IV prostate cancer; recurrent prostate cancer; Recurrent Prostate Carcinoma; stage I multiple myeloma; stage II multiple myeloma; Refractory Plasma Cell Myeloma; bone metastases
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Adenocarcinoma; Neoplasms; Zoledronic Acid

Study Results

Participant Flow

Arm/Group Title	Arm I (Zoledronic Acid Every 4 Weeks)	Arm II (Zoledronic Acid Every 12 Weeks)
Arm/Group Description	Patients receive zoledronic acid IV over at least 15 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.	Patients receive zoledronic acid IV over at least 15 minutes every 12 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
STARTED	911	911
COMPLETED	882	884
NOT COMPLETED	29	27

Baseline Characteristics

Arm/Group Title	Arm I (Zoledronic Acid Every 4 Weeks)	Arm II (Zoledronic Acid Every 12 Weeks)	Total
Arm/Group Description	Patients receive zoledronic acid IV over at least 15 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.	Patients receive zoledronic acid IV over at least 15 minutes every 12 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.	Total of all reporting groups
Overall Participants	911	911	1822
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.3 (12.1)	65.3 (11.7)	65.3 (11.9)
Sex: Female, Male (Count of Participants)
Female	414 45.4%	428 47%	842 46.2%
Male	497 54.6%	483 53%	980 53.8%
Region of Enrollment (participants) [Number]
United States	911 100%	911 100%	1822 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With at Least One Skeletal-related Event (SRE) Within 2 Years After Randomization
Description	To determine whether every-12-week therapy with zoledronic acid is not inferior to every-4-week therapy for patients with metastatic breast cancer, metastatic prostate cancer, or multiple myeloma involving bone, as measured by the proportion of patients who would have experienced at least one skeletal related event within 24 months after randomization.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

All patients that were eligible and completed treatment were analyzed.

Arm/Group Title	Arm I (Zoledronic Acid Every 4 Weeks)	Arm II (Zoledronic Acid Every 12 Weeks)
Arm/Group Description	Patients receive zoledronic acid IV over at least 15 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.	Patients receive zoledronic acid IV over at least 15 minutes every 12 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.
Measure Participants	911	911
Number [percentage of participants]	67.6 7.4%	67.9 7.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Zoledronic Acid Every 4 Weeks), Arm II (Zoledronic Acid Every 12 Weeks)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Based on the published data on the effect of a standard of dosing schedule of > zoledronic acid compared to placebo, we choose ∆= 7%, πT= 42%, and πS= 35%. With a total of 1230 eligible patients (615 per arm), the probability of rejecting the null hypothesis using a one-sided test is at most 0.05 (Type I error α) when θ≥ 7% and the probability of rejecting the null hypothesis (the power) is at least 82% when θ≤0
Statistical Test of Hypothesis	p-Value	<=.05
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

2. Secondary Outcome

Title	Average Pain Intensity Score as Assessed by the Brief Pain Inventory (BPI) Questionnaire
Description	To compare pain scores (Brief Pain Inventory) of patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing. The change scores were evaluated in a general linear model with repeated measures for treatment effect and the time trend with patient-specific characteristics being adjusted for the mean interference score. Specifically the difference in score change per 4 weeks for Arm I using Arm II as the reference is reported. The score of the BPI questionnaire ranges from 0 being no pain to 10 being the most pain. The average score is reported for each arm below.
Time Frame	from baseline up to 2 years

Outcome Measure Data

Analysis Population Description

1766 patients completed treatment and were analyzed.

Arm/Group Title	Arm I (Zoledronic Acid Every 4 Weeks)	Arm II (Zoledronic Acid Every 12 Weeks)
Arm/Group Description	Patients receive zoledronic acid IV over at least 15 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.	Patients receive zoledronic acid IV over at least 15 minutes every 12 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.
Measure Participants	882	884
Mean (Standard Error) [score on a scale]	2.06 (0.14)	2.09 (0.14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Zoledronic Acid Every 4 Weeks), Arm II (Zoledronic Acid Every 12 Weeks)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.68
	Comments
	Method	Mixed Models Analysis
	Comments	Model is adjusted for tumor type, baseline creatinine, prior SREs, prior bisphosphonates, age, gender, race, BSA, and baseline performance status
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	-0.00394
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.009620
	Estimation Comments

3. Secondary Outcome

Title	Average ECOG Performance Status
Description	To compare functional status (ECOG performance status) of patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing. The change scores were evaluated in a general linear model with repeated measures for treatment effect and the time trend with patient-specific characteristics being adjusted. Specifically the difference in score change per 4 weeks for Arm I using Arm II as the reference is reported. ECOG performance status is a measurement of a patients disability ranging from 0, fully active and able to carry out all pre disease performance without restriction, to 5, dead. The average performance status is reported below by arm.
Time Frame	from baseline up to 2 years

Outcome Measure Data

Analysis Population Description

1766 patients completed treatment and were analyzed.

Arm/Group Title	Arm I (Zoledronic Acid Every 4 Weeks)	Arm II (Zoledronic Acid Every 12 Weeks)
Arm/Group Description	Patients receive zoledronic acid IV over at least 15 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.	Patients receive zoledronic acid IV over at least 15 minutes every 12 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.
Measure Participants	882	884
Mean (Standard Error) [score on a scale]	0.82 (0.042)	0.84 (0.042)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Zoledronic Acid Every 4 Weeks), Arm II (Zoledronic Acid Every 12 Weeks)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.64
	Comments
	Method	Mixed Models Analysis
	Comments	Adjusted for tumor type, baseline creatinine, prior SRE, prior bisphosphonates, age, gender, BSA, race, and baseline performance status
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	0.0016
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.0034
	Estimation Comments

4. Secondary Outcome

Title	Incidence of Osteonecrosis of the Jaw
Description	To compare the incidence of osteonecrosis of the jaw in patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing. The percentage of participants with osteonecrosis is reported here.
Time Frame	from baseline up to 2 years

Outcome Measure Data

Analysis Population Description

1766 patients completed treatment and were analyzed.

Arm/Group Title	Arm I (Zoledronic Acid Every 4 Weeks)	Arm II (Zoledronic Acid Every 12 Weeks)
Arm/Group Description	Patients receive zoledronic acid IV over at least 15 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.	Patients receive zoledronic acid IV over at least 15 minutes every 12 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.
Measure Participants	882	884
Number [percentage of participants]	2.0 0.2%	1.0 0.1%

5. Secondary Outcome

Title	Incidence of Renal Dysfunction
Description	To compare the incidence of renal dysfunction of patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing. The percentage of patients with renal dysfunction, defined as grade 3 or grade 4 increased creatinine (Common Terminology Criteria for Adverse Events version 3.0), will be reported here.
Time Frame	from baseline up to 2 years

Outcome Measure Data

Analysis Population Description

1689 patients completed treatment and were analyzed.

Arm/Group Title	Arm I (Zoledronic Acid Every 4 Weeks)	Arm II (Zoledronic Acid Every 12 Weeks)
Arm/Group Description	Patients receive zoledronic acid IV over at least 15 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.	Patients receive zoledronic acid IV over at least 15 minutes every 12 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.
Measure Participants	852	837
Number [percentage of participants]	1.2 0.1%	.5 0.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Zoledronic Acid Every 4 Weeks), Arm II (Zoledronic Acid Every 12 Weeks)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.10
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.7
	Confidence Interval	(2-Sided) 95%; -0.3 to 1.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Skeletal Morbidity Rate
Description	To compare the skeletal morbidity rate, defined as the number of skeletal-related events per year, of patients receiving every 12 week dosing to those receiving every 4 week dosing.
Time Frame	from baseline up to 2 years

Outcome Measure Data

Analysis Population Description

1766 patients were treated and analyzed.

Arm/Group Title	Arm I (Zoledronic Acid Every 4 Weeks)	Arm II (Zoledronic Acid Every 12 Weeks)
Arm/Group Description	Patients receive zoledronic acid IV over at least 15 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.	Patients receive zoledronic acid IV over at least 15 minutes every 12 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.
Measure Participants	882	884
Mean (Standard Deviation) [SRE's per year]	.4 (1.0)	.4 (1.1)

7. Secondary Outcome

Title	Bone Turnover Assessed by Serum C-telopeptide (CTX) Levels (Breast Cancer)
Description	To compare the suppression of serum markers of bone resorption of patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing. The number of patients with high & low CTX values by arm will be reported here.
Time Frame	from baseline up to 2 years

Outcome Measure Data

Analysis Population Description

266 breast cancer patients who were treated and included in this portion of the substudy.

Arm/Group Title	Breast Cancer 4 Weeks	Breast Cancer 12 Weeks
Arm/Group Description	Patients with Breast Cancer receive zoledronic acid IV over at least 15 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.	Patients receive zoledronic acid IV over at least 15 minutes every 12 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.
Measure Participants	137	129
Low CTX (<0.415ng/ml)	83 9.1%	75 8.2%
High CTX (>0.415ng/ml)	54 5.9%	54 5.9%

8. Secondary Outcome

Title	Proportion of Patients Having at Least One SRE Within 24 Months After Randomization for the Subgroups of Patients With Breast Cancer
Description	To determine whether every 12 week therapy with zoledronic acid is not inferior to every-4-week therapy for patients with breast cancer, as measured by the proportion who experience at least one skeletal related event within 24 months after randomization.
Time Frame	from baseline up to 24 months

Outcome Measure Data

Analysis Population Description

820 patients completed treatment and were analyzed.

Arm/Group Title	Breast Cancer 4 Weeks	Breast Cancer 12 Weeks
Arm/Group Description	Patients with Breast Cancer receive zoledronic acid IV over at least 15 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.	Patients receive zoledronic acid IV over at least 15 minutes every 12 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.
Measure Participants	410	410
Count of Participants [Participants]	113 12.4%	119 13.1%

9. Secondary Outcome

Title	Proportion of Patients Having at Least One SRE Within 24 Months After Randomization for the Subgroups of Patients With Prostate Cancer
Description	To determine whether every 12 week therapy with zoledronic acid is not inferior to every-4-week therapy for patients with prostate cancer, as measured by the proportion who experience at least one skeletal related event within 24 months after randomization.
Time Frame	from baseline up to 24 months

Outcome Measure Data

Analysis Population Description

660 patients completed treatment and were analyzed.

Arm/Group Title	Prostate Cancer 4 Weeks	Prostate Cancer 12 Weeks
Arm/Group Description	Patients with Prostate Cancer receive zoledronic acid IV over at least 15 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.	Patients with Prostate Cancer receive zoledronic acid IV over at least 15 minutes every 12 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.
Measure Participants	330	330
Count of Participants [Participants]	107 11.7%	101 11.1%

10. Secondary Outcome

Title	Proportion of Patients Having at Least One SRE Within 24 Months After Randomization for the Subgroups of Patients With Multiple Myeloma
Description	To determine whether every 12 week therapy with zoledronic acid is not inferior to every-4-week therapy for patients with multiple myeloma, as measured by the proportion who experience at least one skeletal related event within 24 months after randomization.
Time Frame	from baseline up to 24 months

Outcome Measure Data

Analysis Population Description

265 patient completed treatment and were analyzed.

Arm/Group Title	Multiple Myeloma 4 Weeks	Multiple Myeloma 12 Weeks
Arm/Group Description	Patients with Breast Cancer receive zoledronic acid IV over at least 15 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.	Patients with Breast Cancer receive zoledronic acid IV over at least 15 minutes every 12 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.
Measure Participants	130	135
Count of Participants [Participants]	35 3.8%	30 3.3%

11. Secondary Outcome

Title	Bone Turnover Assessed by Serum C-telopeptide (CTX) Levels (Prostate Cancer)
Description	To compare the suppression of serum markers of bone resorption of patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing. The number of patients with high & low CTX values by arm will be reported here.
Time Frame	from baseline up to 24 months

Outcome Measure Data

Analysis Population Description

207 prostate cancer patients who were treated and included in this portion of the substudy.

Arm/Group Title	Prostate Cancer 4 Weeks	Prostate Cancer 12 Weeks
Arm/Group Description	Patients with Prostate Cancer receive zoledronic acid IV over at least 15 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.	Patients with Prostate Cancer receive zoledronic acid IV over at least 15 minutes every 12 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.
Measure Participants	104	103
Low CTX (<0.415ng/ml)	34 3.7%	49 5.4%
High CTX (>.0.415ng/ml)	70 7.7%	54 5.9%

12. Secondary Outcome

Title	Bone Turnover Assessed by Serum C-telopeptide (CTX) Levels (Multiple Myeloma)
Description	To compare the suppression of serum markers of bone resorption of patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing. The number of patients with high & low CTX values by arm will be reported here.
Time Frame	from baseline up to 24 months

Outcome Measure Data

Analysis Population Description

74 multiple myeloma patients were treated and included in this portion of the substudy.

Arm/Group Title	Multiple Myeloma 4 Weeks	Multiple Myeloma 12 Weeks
Arm/Group Description	Patients with Breast Cancer receive zoledronic acid IV over at least 15 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.	Patients with Breast Cancer receive zoledronic acid IV over at least 15 minutes every 12 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.
Measure Participants	38	36
Low CTX (<0.415ng/ml)	15 1.6%	19 2.1%
High CTX (>.0.415ng/ml)	23 2.5%	17 1.9%

Adverse Events

Arm/Group Title	Arm I (Zoledronic Acid Every 4 Weeks)		Arm II (Zoledronic Acid Every 12 Weeks)
Arm/Group Description	Patients receive zoledronic acid IV over at least 15 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.		Patients receive zoledronic acid IV over at least 15 minutes every 12 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.
All Cause Mortality
	Arm I (Zoledronic Acid Every 4 Weeks)		Arm II (Zoledronic Acid Every 12 Weeks)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	41/879 (4.7%)		42/868 (4.8%)
Serious Adverse Events
	Arm I (Zoledronic Acid Every 4 Weeks)		Arm II (Zoledronic Acid Every 12 Weeks)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	96/879 (10.9%)		103/868 (11.9%)
Blood and lymphatic system disorders
Bone marrow hypocellular	1/879 (0.1%)	1	0/868 (0%)	0
Disseminated intravascular coagulation	1/879 (0.1%)	1	0/868 (0%)	0
Febrile neutropenia	1/879 (0.1%)	1	4/868 (0.5%)	4
Hemoglobin decreased	8/879 (0.9%)	8	10/868 (1.2%)	11
Hemolysis	2/879 (0.2%)	2	0/868 (0%)	0
Cardiac disorders
Arrhythmia supraventricular	0/879 (0%)	0	1/868 (0.1%)	2
Atrial fibrillation	1/879 (0.1%)	1	1/868 (0.1%)	1
Cardiac disorder	3/879 (0.3%)	3	1/868 (0.1%)	2
Cardiac valve disease	0/879 (0%)	0	1/868 (0.1%)	2
Cardiopulmonary arrest	1/879 (0.1%)	1	0/868 (0%)	0
Conduction disorder	1/879 (0.1%)	1	0/868 (0%)	0
Left ventricular failure	1/879 (0.1%)	2	0/868 (0%)	0
Myocardial ischemia	3/879 (0.3%)	3	0/868 (0%)	0
Pericardial effusion	0/879 (0%)	0	1/868 (0.1%)	1
Restrictive cardiomyopathy	0/879 (0%)	0	1/868 (0.1%)	1
Right ventricular dysfunction	0/879 (0%)	0	1/868 (0.1%)	2
Sinus arrhythmia	0/879 (0%)	0	2/868 (0.2%)	3
Sinus bradycardia	1/879 (0.1%)	1	0/868 (0%)	0
Sinus tachycardia	0/879 (0%)	0	1/868 (0.1%)	1
Supraventricular tachycardia	0/879 (0%)	0	3/868 (0.3%)	3
Ventricular tachycardia	1/879 (0.1%)	1	0/868 (0%)	0
Gastrointestinal disorders
Abdominal distension	2/879 (0.2%)	2	0/868 (0%)	0
Abdominal pain	3/879 (0.3%)	3	3/868 (0.3%)	3
Ascites	1/879 (0.1%)	1	0/868 (0%)	0
Colitis	2/879 (0.2%)	2	0/868 (0%)	0
Colonic perforation	1/879 (0.1%)	1	0/868 (0%)	0
Constipation	8/879 (0.9%)	8	12/868 (1.4%)	14
Diarrhea	12/879 (1.4%)	13	11/868 (1.3%)	11
Duodenal obstruction	1/879 (0.1%)	1	0/868 (0%)	0
Dysphagia	1/879 (0.1%)	1	0/868 (0%)	0
Gastric ulcer	0/879 (0%)	0	1/868 (0.1%)	1
Gastrointestinal disorder	0/879 (0%)	0	1/868 (0.1%)	1
Mucositis oral	1/879 (0.1%)	1	0/868 (0%)	0
Nausea	13/879 (1.5%)	13	16/868 (1.8%)	17
Oral pain	0/879 (0%)	0	2/868 (0.2%)	2
Pancreatitis	0/879 (0%)	0	1/868 (0.1%)	1
Proctitis	1/879 (0.1%)	1	0/868 (0%)	0
Vomiting	9/879 (1%)	9	9/868 (1%)	10
General disorders
Chest pain	1/879 (0.1%)	1	0/868 (0%)	0
Death NOS	14/879 (1.6%)	14	14/868 (1.6%)	14
Disease progression	10/879 (1.1%)	10	15/868 (1.7%)	15
Edema limbs	1/879 (0.1%)	1	3/868 (0.3%)	4
Fatigue	6/879 (0.7%)	6	9/868 (1%)	10
Fever	3/879 (0.3%)	3	9/868 (1%)	9
Flu-like symptoms	0/879 (0%)	0	1/868 (0.1%)	1
General symptom	1/879 (0.1%)	1	1/868 (0.1%)	2
Multi-organ failure	2/879 (0.2%)	2	1/868 (0.1%)	1
Pain	3/879 (0.3%)	3	1/868 (0.1%)	1
Hepatobiliary disorders
Biliary fistula	1/879 (0.1%)	1	0/868 (0%)	0
Cholecystitis	0/879 (0%)	0	1/868 (0.1%)	1
Gallbladder necrosis	0/879 (0%)	0	1/868 (0.1%)	1
Hepatic failure	0/879 (0%)	0	1/868 (0.1%)	1
Infections and infestations
Bladder infection	0/879 (0%)	0	1/868 (0.1%)	1
Bone infection	0/879 (0%)	0	1/868 (0.1%)	1
Infection	3/879 (0.3%)	3	2/868 (0.2%)	2
Pneumonia	2/879 (0.2%)	2	4/868 (0.5%)	5
Sepsis	1/879 (0.1%)	1	1/868 (0.1%)	1
Skin infection	2/879 (0.2%)	2	1/868 (0.1%)	1
Urinary tract infection	3/879 (0.3%)	3	2/868 (0.2%)	2
Injury, poisoning and procedural complications
Intraoperative musculoskeletal injury	1/879 (0.1%)	1	0/868 (0%)	0
Intraoperative neurological injury - Spinal cord	1/879 (0.1%)	1	0/868 (0%)	0
Vascular access complication	1/879 (0.1%)	1	0/868 (0%)	0
Investigations
Activated partial thromboplastin time prolonged	1/879 (0.1%)	1	0/868 (0%)	0
Alanine aminotransferase increased	4/879 (0.5%)	4	2/868 (0.2%)	2
Alkaline phosphatase increased	3/879 (0.3%)	3	2/868 (0.2%)	3
Aspartate aminotransferase increased	9/879 (1%)	9	1/868 (0.1%)	1
Blood bilirubin increased	2/879 (0.2%)	2	1/868 (0.1%)	1
Cardiac troponin I increased	1/879 (0.1%)	1	0/868 (0%)	0
Cardiac troponin T increased	2/879 (0.2%)	2	0/868 (0%)	0
Creatine phosphokinase increased	0/879 (0%)	0	1/868 (0.1%)	1
Creatinine increased	2/879 (0.2%)	2	1/868 (0.1%)	1
Electrocardiogram QTc interval prolonged	0/879 (0%)	0	1/868 (0.1%)	1
INR increased	0/879 (0%)	0	1/868 (0.1%)	1
Leukocyte count decreased	0/879 (0%)	0	4/868 (0.5%)	4
Lymphocyte count decreased	4/879 (0.5%)	4	6/868 (0.7%)	6
Neutrophil count decreased	2/879 (0.2%)	2	6/868 (0.7%)	6
Platelet count decreased	5/879 (0.6%)	5	4/868 (0.5%)	4
Weight loss	2/879 (0.2%)	2	2/868 (0.2%)	2
Metabolism and nutrition disorders
Acidosis	0/879 (0%)	0	2/868 (0.2%)	2
Alkalosis	0/879 (0%)	0	2/868 (0.2%)	2
Anorexia	2/879 (0.2%)	2	1/868 (0.1%)	1
Blood glucose increased	1/879 (0.1%)	1	5/868 (0.6%)	5
Dehydration	4/879 (0.5%)	4	4/868 (0.5%)	6
Obesity	0/879 (0%)	0	1/868 (0.1%)	2
Serum albumin decreased	1/879 (0.1%)	1	5/868 (0.6%)	5
Serum calcium decreased	28/879 (3.2%)	32	34/868 (3.9%)	39
Serum calcium increased	1/879 (0.1%)	1	1/868 (0.1%)	1
Serum glucose decreased	0/879 (0%)	0	2/868 (0.2%)	2
Serum magnesium increased	7/879 (0.8%)	8	9/868 (1%)	10
Serum phosphate decreased	4/879 (0.5%)	5	11/868 (1.3%)	11
Serum potassium decreased	5/879 (0.6%)	6	6/868 (0.7%)	6
Serum potassium increased	2/879 (0.2%)	2	2/868 (0.2%)	2
Serum sodium decreased	1/879 (0.1%)	1	11/868 (1.3%)	12
Musculoskeletal and connective tissue disorders
Arthralgia	2/879 (0.2%)	2	1/868 (0.1%)	1
Back pain	8/879 (0.9%)	8	4/868 (0.5%)	4
Bone pain	5/879 (0.6%)	5	3/868 (0.3%)	3
Buttock pain	1/879 (0.1%)	1	0/868 (0%)	0
Chest wall pain	0/879 (0%)	0	1/868 (0.1%)	1
Muscle weakness	1/879 (0.1%)	1	4/868 (0.5%)	4
Osteonecrosis	4/879 (0.5%)	4	4/868 (0.5%)	4
Pain in extremity	2/879 (0.2%)	2	1/868 (0.1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Myelodysplasia	0/879 (0%)	0	1/868 (0.1%)	1
Treatment related secondary malignancy	0/879 (0%)	0	1/868 (0.1%)	1
Nervous system disorders
Cognitive disturbance	0/879 (0%)	0	1/868 (0.1%)	1
Depressed level of consciousness	0/879 (0%)	0	2/868 (0.2%)	2
Dizziness	0/879 (0%)	0	1/868 (0.1%)	1
Intracranial hemorrhage	1/879 (0.1%)	1	1/868 (0.1%)	1
Ischemia cerebrovascular	3/879 (0.3%)	3	1/868 (0.1%)	1
Peripheral sensory neuropathy	1/879 (0.1%)	1	1/868 (0.1%)	1
Syncope	1/879 (0.1%)	1	2/868 (0.2%)	2
Psychiatric disorders
Confusion	0/879 (0%)	0	4/868 (0.5%)	5
Depression	1/879 (0.1%)	1	1/868 (0.1%)	1
Insomnia	2/879 (0.2%)	2	0/868 (0%)	0
Renal and urinary disorders
Renal failure	1/879 (0.1%)	1	1/868 (0.1%)	1
Urinary incontinence	1/879 (0.1%)	1	1/868 (0.1%)	1
Urogenital disorder	23/879 (2.6%)	30	18/868 (2.1%)	22
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome	0/879 (0%)	0	1/868 (0.1%)	1
Apnea	0/879 (0%)	0	1/868 (0.1%)	2
Aspiration	2/879 (0.2%)	2	0/868 (0%)	0
Cough	1/879 (0.1%)	1	3/868 (0.3%)	3
Dyspnea	6/879 (0.7%)	6	7/868 (0.8%)	8
Hypoxia	6/879 (0.7%)	6	5/868 (0.6%)	6
Pharyngolaryngeal pain	0/879 (0%)	0	1/868 (0.1%)	1
Pleural effusion	1/879 (0.1%)	1	2/868 (0.2%)	2
Pneumonitis	1/879 (0.1%)	1	2/868 (0.2%)	2
Respiratory disorder	1/879 (0.1%)	1	4/868 (0.5%)	5
Skin and subcutaneous tissue disorders
Pain of skin	0/879 (0%)	0	1/868 (0.1%)	1
Vascular disorders
Hematoma	0/879 (0%)	0	1/868 (0.1%)	1
Hemorrhage	1/879 (0.1%)	1	1/868 (0.1%)	1
Hypertension	0/879 (0%)	0	1/868 (0.1%)	1
Hypotension	3/879 (0.3%)	3	9/868 (1%)	9
Thrombosis	2/879 (0.2%)	4	9/868 (1%)	9
Other (Not Including Serious) Adverse Events
	Arm I (Zoledronic Acid Every 4 Weeks)		Arm II (Zoledronic Acid Every 12 Weeks)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	779/879 (88.6%)		750/868 (86.4%)
Blood and lymphatic system disorders
Blood disorder	2/879 (0.2%)	2	2/868 (0.2%)	2
Febrile neutropenia	10/879 (1.1%)	14	7/868 (0.8%)	8
Hemoglobin decreased	98/879 (11.1%)	195	92/868 (10.6%)	206
Hemolysis	16/879 (1.8%)	37	11/868 (1.3%)	29
Lymphatic disorder	3/879 (0.3%)	5	1/868 (0.1%)	1
Thrombotic microangiopathy	4/879 (0.5%)	5	1/868 (0.1%)	2
Cardiac disorders
Atrial fibrillation	9/879 (1%)	9	2/868 (0.2%)	2
Atrial flutter	1/879 (0.1%)	1	0/868 (0%)	0
Atrial tachycardia	0/879 (0%)	0	1/868 (0.1%)	1
Cardiac disorder	3/879 (0.3%)	3	4/868 (0.5%)	4
Cardiac pain	2/879 (0.2%)	2	1/868 (0.1%)	1
Cardiac valve disease	0/879 (0%)	0	2/868 (0.2%)	2
Left ventricular dysfunction	4/879 (0.5%)	4	3/868 (0.3%)	3
Left ventricular failure	7/879 (0.8%)	8	2/868 (0.2%)	3
Myocardial ischemia	7/879 (0.8%)	7	1/868 (0.1%)	2
Palpitations	0/879 (0%)	0	2/868 (0.2%)	2
Pericardial effusion	2/879 (0.2%)	2	1/868 (0.1%)	1
Pericarditis	0/879 (0%)	0	1/868 (0.1%)	1
Restrictive cardiomyopathy	2/879 (0.2%)	2	2/868 (0.2%)	2
Sick sinus syndrome	0/879 (0%)	0	1/868 (0.1%)	1
Sinus tachycardia	1/879 (0.1%)	1	1/868 (0.1%)	1
Ventricular tachycardia	1/879 (0.1%)	1	1/868 (0.1%)	1
Ear and labyrinth disorders
Ear pain	2/879 (0.2%)	2	1/868 (0.1%)	1
External ear inflammation	0/879 (0%)	0	1/868 (0.1%)	1
External ear pain	0/879 (0%)	0	1/868 (0.1%)	1
Hearing impaired	3/879 (0.3%)	8	1/868 (0.1%)	1
Middle ear inflammation	0/879 (0%)	0	1/868 (0.1%)	2
Tinnitus	1/879 (0.1%)	2	1/868 (0.1%)	5
Endocrine disorders
Cushingoid	1/879 (0.1%)	1	1/868 (0.1%)	2
Endocrine disorder	0/879 (0%)	0	1/868 (0.1%)	1
Eye disorders
Cataract	4/879 (0.5%)	5	3/868 (0.3%)	3
Diplopia	1/879 (0.1%)	6	2/868 (0.2%)	3
Dry eye syndrome	0/879 (0%)	0	1/868 (0.1%)	2
Extraocular muscle paresis	1/879 (0.1%)	1	0/868 (0%)	0
Eye disorder	4/879 (0.5%)	5	5/868 (0.6%)	23
Optic nerve disorder	0/879 (0%)	0	1/868 (0.1%)	1
Retinal detachment	0/879 (0%)	0	1/868 (0.1%)	1
Vision blurred	2/879 (0.2%)	2	2/868 (0.2%)	2
Vitreous hemorrhage	0/879 (0%)	0	1/868 (0.1%)	1
Watering eyes	1/879 (0.1%)	1	1/868 (0.1%)	1
Gastrointestinal disorders
Abdominal distension	5/879 (0.6%)	6	2/868 (0.2%)	2
Abdominal pain	40/879 (4.6%)	74	42/868 (4.8%)	68
Anal exam abnormal	1/879 (0.1%)	2	0/868 (0%)	0
Anal fistula	1/879 (0.1%)	1	0/868 (0%)	0
Ascites	7/879 (0.8%)	15	1/868 (0.1%)	2
Colitis	4/879 (0.5%)	4	3/868 (0.3%)	3
Colonic obstruction	1/879 (0.1%)	1	1/868 (0.1%)	1
Constipation	348/879 (39.6%)	1527	333/868 (38.4%)	1341
Dental prosthesis user	2/879 (0.2%)	5	2/868 (0.2%)	10
Diarrhea	276/879 (31.4%)	693	275/868 (31.7%)	754
Dry mouth	5/879 (0.6%)	5	4/868 (0.5%)	25
Duodenal hemorrhage	0/879 (0%)	0	1/868 (0.1%)	1
Duodenal ulcer	0/879 (0%)	0	1/868 (0.1%)	1
Dyspepsia	4/879 (0.5%)	4	3/868 (0.3%)	6
Dysphagia	3/879 (0.3%)	3	6/868 (0.7%)	11
Ear, nose and throat examination abnormal	4/879 (0.5%)	4	2/868 (0.2%)	4
Esophageal hemorrhage	1/879 (0.1%)	2	0/868 (0%)	0
Esophageal mucositis	1/879 (0.1%)	1	0/868 (0%)	0
Esophageal pain	2/879 (0.2%)	2	2/868 (0.2%)	2
Esophagitis	2/879 (0.2%)	2	1/868 (0.1%)	1
Fecal incontinence	0/879 (0%)	0	1/868 (0.1%)	1
Flatulence	1/879 (0.1%)	1	1/868 (0.1%)	1
Gastric hemorrhage	2/879 (0.2%)	6	1/868 (0.1%)	1
Gastric ulcer	0/879 (0%)	0	1/868 (0.1%)	1
Gastritis	3/879 (0.3%)	4	0/868 (0%)	0
Gastrointestinal disorder	4/879 (0.5%)	4	4/868 (0.5%)	4
Gingival pain	6/879 (0.7%)	9	6/868 (0.7%)	6
Hemorrhoids	1/879 (0.1%)	1	1/868 (0.1%)	1
Ileus	1/879 (0.1%)	1	1/868 (0.1%)	1
Mucositis oral	2/879 (0.2%)	2	5/868 (0.6%)	6
Nausea	367/879 (41.8%)	1187	357/868 (41.1%)	1069
Oesophagoscopy abnormal	1/879 (0.1%)	1	0/868 (0%)	0
Oral pain	7/879 (0.8%)	8	6/868 (0.7%)	15
Pancreatitis	1/879 (0.1%)	1	0/868 (0%)	0
Rectal hemorrhage	0/879 (0%)	0	2/868 (0.2%)	2
Rectal pain	1/879 (0.1%)	1	0/868 (0%)	0
Small intestinal obstruction	1/879 (0.1%)	1	3/868 (0.3%)	3
Stomach pain	2/879 (0.2%)	2	5/868 (0.6%)	7
Tooth development disorder	1/879 (0.1%)	1	0/868 (0%)	0
Toothache	4/879 (0.5%)	4	6/868 (0.7%)	12
Upper gastrointestinal hemorrhage	1/879 (0.1%)	1	1/868 (0.1%)	1
Vomiting	224/879 (25.5%)	441	198/868 (22.8%)	366
General disorders
Chest pain	12/879 (1.4%)	14	19/868 (2.2%)	50
Chills	3/879 (0.3%)	4	0/868 (0%)	0
Edema limbs	16/879 (1.8%)	26	22/868 (2.5%)	51
Facial pain	4/879 (0.5%)	11	0/868 (0%)	0
Fatigue	90/879 (10.2%)	216	87/868 (10%)	260
Fever	173/879 (19.7%)	291	189/868 (21.8%)	298
Flu-like symptoms	2/879 (0.2%)	12	4/868 (0.5%)	4
Gait abnormal	4/879 (0.5%)	4	1/868 (0.1%)	1
General symptom	1/879 (0.1%)	1	1/868 (0.1%)	1
Ill-defined disorder	1/879 (0.1%)	1	1/868 (0.1%)	1
Injection site reaction	1/879 (0.1%)	1	0/868 (0%)	0
Localized edema	1/879 (0.1%)	1	1/868 (0.1%)	1
Pain	97/879 (11%)	275	68/868 (7.8%)	157
Hepatobiliary disorders
Bile duct stenosis	0/879 (0%)	0	1/868 (0.1%)	1
Cholecystitis	1/879 (0.1%)	1	4/868 (0.5%)	4
Gallbladder obstruction	2/879 (0.2%)	3	0/868 (0%)	0
Gallbladder pain	0/879 (0%)	0	2/868 (0.2%)	2
Hepatic pain	4/879 (0.5%)	5	1/868 (0.1%)	6
Immune system disorders
Hypersensitivity	1/879 (0.1%)	1	1/868 (0.1%)	1
Infections and infestations
Abdominal infection	1/879 (0.1%)	1	0/868 (0%)	0
Anal infection	1/879 (0.1%)	1	0/868 (0%)	0
Appendicitis perforated	1/879 (0.1%)	1	0/868 (0%)	0
Bladder infection	3/879 (0.3%)	3	2/868 (0.2%)	2
Bone infection	6/879 (0.7%)	6	1/868 (0.1%)	1
Bronchitis	3/879 (0.3%)	3	0/868 (0%)	0
Catheter related infection	7/879 (0.8%)	11	2/868 (0.2%)	3
Colitis, infectious (e.g., Clostridium difficile)	1/879 (0.1%)	2	1/868 (0.1%)	3
Device related infection	0/879 (0%)	0	3/868 (0.3%)	3
Endocarditis infective	1/879 (0.1%)	1	0/868 (0%)	0
Esophageal infection	0/879 (0%)	0	2/868 (0.2%)	2
Eye infection	1/879 (0.1%)	1	0/868 (0%)	0
Gallbladder infection	0/879 (0%)	0	1/868 (0.1%)	1
Gingival infection	1/879 (0.1%)	1	0/868 (0%)	0
Ileal infection	1/879 (0.1%)	1	0/868 (0%)	0
Infection	12/879 (1.4%)	17	16/868 (1.8%)	20
Joint infection	1/879 (0.1%)	2	0/868 (0%)	0
Lip infection	0/879 (0%)	0	1/868 (0.1%)	1
Lymph gland infection	0/879 (0%)	0	1/868 (0.1%)	1
Mucosal infection	1/879 (0.1%)	1	0/868 (0%)	0
Nail infection	0/879 (0%)	0	1/868 (0.1%)	1
Opportunistic infection	1/879 (0.1%)	1	2/868 (0.2%)	2
Peripheral nerve infection	2/879 (0.2%)	2	2/868 (0.2%)	2
Pharyngitis	0/879 (0%)	0	2/868 (0.2%)	2
Pneumonia	16/879 (1.8%)	17	19/868 (2.2%)	20
Prostate infection	1/879 (0.1%)	1	0/868 (0%)	0
Rhinitis infective	0/879 (0%)	0	1/868 (0.1%)	1
Sepsis	3/879 (0.3%)	3	3/868 (0.3%)	3
Sinusitis	3/879 (0.3%)	3	1/868 (0.1%)	1
Skin infection	13/879 (1.5%)	14	5/868 (0.6%)	5
Small intestine infection	1/879 (0.1%)	1	0/868 (0%)	0
Soft tissue infection	0/879 (0%)	0	2/868 (0.2%)	2
Tooth infection	5/879 (0.6%)	6	2/868 (0.2%)	3
Upper aerodigestive tract infection	0/879 (0%)	0	1/868 (0.1%)	1
Upper respiratory infection	1/879 (0.1%)	1	0/868 (0%)	0
Ureteritis	1/879 (0.1%)	1	0/868 (0%)	0
Urinary tract infection	19/879 (2.2%)	22	13/868 (1.5%)	14
Uterine infection	1/879 (0.1%)	1	0/868 (0%)	0
Wound infection	2/879 (0.2%)	3	1/868 (0.1%)	2
Injury, poisoning and procedural complications
Arterial injury	0/879 (0%)	0	2/868 (0.2%)	2
Bruising	1/879 (0.1%)	1	0/868 (0%)	0
Fracture	7/879 (0.8%)	8	14/868 (1.6%)	28
Gastrointestinal stoma necrosis	1/879 (0.1%)	1	0/868 (0%)	0
Intraoperative complications	2/879 (0.2%)	2	1/868 (0.1%)	1
Intraoperative musculoskeletal injury - Extremity-lower	1/879 (0.1%)	1	1/868 (0.1%)	1
Intraoperative neurological injury	1/879 (0.1%)	1	0/868 (0%)	0
Intraoperative neurological injury - NERVES: Sacral plexus	0/879 (0%)	0	1/868 (0.1%)	2
Prolonged intubation after pulmonary resection (>24 hrs after surgery)	1/879 (0.1%)	1	0/868 (0%)	0
Radiation recall reaction (dermatologic)	0/879 (0%)	0	2/868 (0.2%)	3
Thermal burn	0/879 (0%)	0	1/868 (0.1%)	2
Vascular access complication	2/879 (0.2%)	2	3/868 (0.3%)	4
Investigations
ADH abnormal	0/879 (0%)	0	1/868 (0.1%)	1
Activated partial thromboplastin time prolonged	2/879 (0.2%)	2	2/868 (0.2%)	2
Alanine aminotransferase increased	20/879 (2.3%)	27	14/868 (1.6%)	23
Alkaline phosphatase increased	46/879 (5.2%)	99	34/868 (3.9%)	80
Amylase increased	0/879 (0%)	0	1/868 (0.1%)	1
Aspartate aminotransferase increased	39/879 (4.4%)	58	23/868 (2.6%)	29
Blood bilirubin increased	15/879 (1.7%)	17	12/868 (1.4%)	18
Cardiac troponin I increased	0/879 (0%)	0	2/868 (0.2%)	2
Cardiac troponin T increased	2/879 (0.2%)	2	0/868 (0%)	0
Coagulopathy	0/879 (0%)	0	2/868 (0.2%)	2
Creatine phosphokinase increased	2/879 (0.2%)	4	2/868 (0.2%)	2
Creatinine increased	14/879 (1.6%)	23	10/868 (1.2%)	10
Gamma-glutamyltransferase increased	1/879 (0.1%)	2	0/868 (0%)	0
INR increased	8/879 (0.9%)	28	4/868 (0.5%)	18
Laboratory test abnormal	4/879 (0.5%)	6	0/868 (0%)	0
Leukocyte count decreased	68/879 (7.7%)	128	70/868 (8.1%)	160
Lipase increased	1/879 (0.1%)	1	2/868 (0.2%)	3
Lymphocyte count decreased	41/879 (4.7%)	126	45/868 (5.2%)	143
Neutrophil count decreased	79/879 (9%)	131	70/868 (8.1%)	118
Platelet count decreased	53/879 (6%)	108	59/868 (6.8%)	138
Serum cholesterol increased	0/879 (0%)	0	1/868 (0.1%)	1
Weight gain	4/879 (0.5%)	24	6/868 (0.7%)	32
Weight loss	11/879 (1.3%)	27	14/868 (1.6%)	30
Metabolism and nutrition disorders
Acidosis	1/879 (0.1%)	1	0/868 (0%)	0
Alkalosis	1/879 (0.1%)	1	1/868 (0.1%)	1
Anorexia	28/879 (3.2%)	48	24/868 (2.8%)	39
Blood bicarbonate decreased	0/879 (0%)	0	3/868 (0.3%)	3
Blood glucose increased	43/879 (4.9%)	150	57/868 (6.6%)	181
Blood uric acid increased	0/879 (0%)	0	1/868 (0.1%)	1
Dehydration	20/879 (2.3%)	23	22/868 (2.5%)	22
Obesity	0/879 (0%)	0	2/868 (0.2%)	29
Serum albumin decreased	22/879 (2.5%)	30	12/868 (1.4%)	18
Serum calcium decreased	320/879 (36.4%)	996	290/868 (33.4%)	839
Serum calcium increased	87/879 (9.9%)	177	82/868 (9.4%)	207
Serum glucose decreased	4/879 (0.5%)	5	5/868 (0.6%)	9
Serum magnesium increased	56/879 (6.4%)	101	61/868 (7%)	93
Serum phosphate decreased	64/879 (7.3%)	95	69/868 (7.9%)	130
Serum potassium decreased	30/879 (3.4%)	41	26/868 (3%)	45
Serum potassium increased	11/879 (1.3%)	13	11/868 (1.3%)	12
Serum sodium decreased	31/879 (3.5%)	45	28/868 (3.2%)	38
Serum sodium increased	1/879 (0.1%)	1	2/868 (0.2%)	2
Serum triglycerides increased	1/879 (0.1%)	1	1/868 (0.1%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	93/879 (10.6%)	307	83/868 (9.6%)	311
Arthritis	9/879 (1%)	20	4/868 (0.5%)	8
Back pain	191/879 (21.7%)	792	177/868 (20.4%)	688
Bone pain	139/879 (15.8%)	595	131/868 (15.1%)	452
Buttock pain	24/879 (2.7%)	52	17/868 (2%)	32
Chest wall pain	25/879 (2.8%)	74	21/868 (2.4%)	39
Fibrosis	1/879 (0.1%)	1	0/868 (0%)	0
Fibrosis deep connective tissue	0/879 (0%)	0	1/868 (0.1%)	1
Joint disorder	1/879 (0.1%)	1	1/868 (0.1%)	1
Joint range of motion decreased cervical spine	0/879 (0%)	0	1/868 (0.1%)	1
Joint range of motion decreased lumbar spine	0/879 (0%)	0	1/868 (0.1%)	4
Muscle weakness	22/879 (2.5%)	27	19/868 (2.2%)	22
Muscle weakness left-sided	0/879 (0%)	0	3/868 (0.3%)	3
Muscle weakness lower limb	5/879 (0.6%)	16	5/868 (0.6%)	8
Muscle weakness right-sided	0/879 (0%)	0	1/868 (0.1%)	1
Muscle weakness trunk	0/879 (0%)	0	1/868 (0.1%)	2
Muscle weakness upper limb	3/879 (0.3%)	7	1/868 (0.1%)	1
Musculoskeletal disorder	4/879 (0.5%)	7	3/868 (0.3%)	3
Myalgia	46/879 (5.2%)	73	44/868 (5.1%)	79
Myositis	1/879 (0.1%)	1	0/868 (0%)	0
Neck pain	29/879 (3.3%)	58	38/868 (4.4%)	79
Osteonecrosis	15/879 (1.7%)	20	5/868 (0.6%)	10
Osteoporosis	1/879 (0.1%)	3	1/868 (0.1%)	1
Pain in extremity	114/879 (13%)	318	92/868 (10.6%)	311
Soft tissue necrosis upper limb	0/879 (0%)	0	1/868 (0.1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Myelodysplasia	1/879 (0.1%)	1	0/868 (0%)	0
Treatment related secondary malignancy	7/879 (0.8%)	7	6/868 (0.7%)	6
Tumor pain	4/879 (0.5%)	4	3/868 (0.3%)	4
Nervous system disorders
Acoustic nerve disorder NOS	0/879 (0%)	0	1/868 (0.1%)	1
Arachnoiditis	1/879 (0.1%)	3	0/868 (0%)	0
Ataxia	3/879 (0.3%)	3	1/868 (0.1%)	1
Cognitive disturbance	0/879 (0%)	0	1/868 (0.1%)	1
Depressed level of consciousness	5/879 (0.6%)	5	3/868 (0.3%)	3
Dizziness	15/879 (1.7%)	30	16/868 (1.8%)	27
Dysgeusia	2/879 (0.2%)	2	0/868 (0%)	0
Encephalopathy	2/879 (0.2%)	2	1/868 (0.1%)	1
Extrapyramidal disorder	2/879 (0.2%)	2	1/868 (0.1%)	1
Facial muscle weakness	0/879 (0%)	0	1/868 (0.1%)	1
Facial nerve disorder	3/879 (0.3%)	9	0/868 (0%)	0
Headache	29/879 (3.3%)	58	37/868 (4.3%)	63
Intracranial hemorrhage	1/879 (0.1%)	1	1/868 (0.1%)	1
Ischemia cerebrovascular	2/879 (0.2%)	2	6/868 (0.7%)	6
Memory impairment	2/879 (0.2%)	4	1/868 (0.1%)	1
Neuralgia	4/879 (0.5%)	8	7/868 (0.8%)	8
Neurological disorder NOS	7/879 (0.8%)	10	3/868 (0.3%)	3
Peripheral motor neuropathy	17/879 (1.9%)	33	11/868 (1.3%)	18
Peripheral sensory neuropathy	33/879 (3.8%)	91	51/868 (5.9%)	215
Pyramidal tract syndrome	0/879 (0%)	0	1/868 (0.1%)	1
Radiculitis brachial	1/879 (0.1%)	1	0/868 (0%)	0
Seizure	0/879 (0%)	0	6/868 (0.7%)	7
Sinus pain	1/879 (0.1%)	2	2/868 (0.2%)	2
Speech disorder	2/879 (0.2%)	2	1/868 (0.1%)	1
Syncope	14/879 (1.6%)	20	11/868 (1.3%)	15
Syncope vasovagal	0/879 (0%)	0	1/868 (0.1%)	1
Tremor	1/879 (0.1%)	1	1/868 (0.1%)	1
Psychiatric disorders
Agitation	1/879 (0.1%)	10	0/868 (0%)	0
Anxiety	4/879 (0.5%)	6	4/868 (0.5%)	5
Confusion	4/879 (0.5%)	14	6/868 (0.7%)	6
Depression	4/879 (0.5%)	6	12/868 (1.4%)	25
Insomnia	6/879 (0.7%)	16	6/868 (0.7%)	11
Libido decreased	1/879 (0.1%)	1	0/868 (0%)	0
Psychosis	2/879 (0.2%)	2	1/868 (0.1%)	1
Renal and urinary disorders
Bladder pain	0/879 (0%)	0	2/868 (0.2%)	2
Bladder stenosis	0/879 (0%)	0	1/868 (0.1%)	1
Cystitis	2/879 (0.2%)	2	1/868 (0.1%)	1
Hemoglobin urine positive	1/879 (0.1%)	1	0/868 (0%)	0
Hemorrhage urinary tract	2/879 (0.2%)	3	0/868 (0%)	0
Kidney pain	3/879 (0.3%)	3	4/868 (0.5%)	4
Kidney perforation	1/879 (0.1%)	1	0/868 (0%)	0
Proteinuria	0/879 (0%)	0	2/868 (0.2%)	2
Renal failure	1/879 (0.1%)	1	1/868 (0.1%)	1
Ureteric obstruction	1/879 (0.1%)	1	2/868 (0.2%)	2
Ureteric stenosis	0/879 (0%)	0	2/868 (0.2%)	2
Urethral hemorrhage	0/879 (0%)	0	1/868 (0.1%)	1
Urethral obstruction	1/879 (0.1%)	1	1/868 (0.1%)	1
Urinary frequency	1/879 (0.1%)	1	8/868 (0.9%)	13
Urinary incontinence	4/879 (0.5%)	19	2/868 (0.2%)	4
Urinary retention	4/879 (0.5%)	6	4/868 (0.5%)	4
Urogenital disorder	183/879 (20.8%)	794	159/868 (18.3%)	677
Reproductive system and breast disorders
Breast pain	7/879 (0.8%)	42	10/868 (1.2%)	16
Erectile dysfunction	0/879 (0%)	0	1/868 (0.1%)	3
Pelvic pain	14/879 (1.6%)	31	9/868 (1%)	12
Penile pain	0/879 (0%)	0	1/868 (0.1%)	3
Prostatic pain	1/879 (0.1%)	1	0/868 (0%)	0
Scrotal pain	2/879 (0.2%)	2	0/868 (0%)	0
Vaginal pain	0/879 (0%)	0	1/868 (0.1%)	1
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome	0/879 (0%)	0	1/868 (0.1%)	2
Allergic rhinitis	1/879 (0.1%)	2	2/868 (0.2%)	4
Apnea	1/879 (0.1%)	5	0/868 (0%)	0
Aspiration	0/879 (0%)	0	1/868 (0.1%)	1
Atelectasis	0/879 (0%)	0	1/868 (0.1%)	1
Bronchospasm	1/879 (0.1%)	1	0/868 (0%)	0
Cough	8/879 (0.9%)	8	12/868 (1.4%)	33
Dyspnea	42/879 (4.8%)	71	51/868 (5.9%)	78
Epistaxis	1/879 (0.1%)	1	3/868 (0.3%)	4
Hiccups	1/879 (0.1%)	1	0/868 (0%)	0
Hypoxia	7/879 (0.8%)	8	14/868 (1.6%)	14
Pharyngeal examination abnormal	1/879 (0.1%)	1	0/868 (0%)	0
Pharyngolaryngeal pain	4/879 (0.5%)	5	2/868 (0.2%)	2
Pleural effusion	7/879 (0.8%)	8	13/868 (1.5%)	30
Pleuritic pain	1/879 (0.1%)	1	2/868 (0.2%)	2
Pneumonitis	3/879 (0.3%)	4	6/868 (0.7%)	6
Pneumothorax	0/879 (0%)	0	1/868 (0.1%)	1
Pulmonary hypertension	1/879 (0.1%)	1	2/868 (0.2%)	2
Respiratory disorder	1/879 (0.1%)	1	2/868 (0.2%)	2
Respiratory tract hemorrhage	0/879 (0%)	0	1/868 (0.1%)	1
Voice alteration	0/879 (0%)	0	1/868 (0.1%)	1
Skin and subcutaneous tissue disorders
Alopecia	4/879 (0.5%)	11	4/868 (0.5%)	8
Decubitus ulcer	1/879 (0.1%)	1	2/868 (0.2%)	2
Dry skin	0/879 (0%)	0	1/868 (0.1%)	2
Erythema multiforme	1/879 (0.1%)	2	4/868 (0.5%)	4
Hand-and-foot syndrome	12/879 (1.4%)	21	8/868 (0.9%)	39
Nail disorder	1/879 (0.1%)	1	2/868 (0.2%)	2
Pain of skin	2/879 (0.2%)	2	1/868 (0.1%)	2
Photosensitivity	0/879 (0%)	0	1/868 (0.1%)	1
Pruritus	2/879 (0.2%)	2	3/868 (0.3%)	6
Rash acneiform	1/879 (0.1%)	1	0/868 (0%)	0
Rash desquamating	7/879 (0.8%)	13	7/868 (0.8%)	19
Skin disorder	4/879 (0.5%)	6	4/868 (0.5%)	5
Skin hyperpigmentation	2/879 (0.2%)	4	4/868 (0.5%)	6
Skin hypopigmentation	2/879 (0.2%)	3	1/868 (0.1%)	13
Skin ulceration	1/879 (0.1%)	2	1/868 (0.1%)	2
Sweating	3/879 (0.3%)	3	2/868 (0.2%)	2
Vascular disorders
Hematoma	0/879 (0%)	0	1/868 (0.1%)	1
Hemorrhage	0/879 (0%)	0	2/868 (0.2%)	2
Hot flashes	2/879 (0.2%)	2	9/868 (1%)	32
Hypertension	32/879 (3.6%)	75	21/868 (2.4%)	55
Hypotension	8/879 (0.9%)	9	12/868 (1.4%)	12
Peripheral ischemia	1/879 (0.1%)	1	0/868 (0%)	0
Thrombosis	23/879 (2.6%)	34	24/868 (2.8%)	47
Vascular disorder	1/879 (0.1%)	1	1/868 (0.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.