Zoledronate, Calcium, and Vitamin D in Preventing Bone Loss in Women Receiving Adjuvant Chemotherapy for Breast Cancer

Sponsor

Alliance for Clinical Trials in Oncology (Other)

Overall Status

Completed

CT.gov ID

NCT00022087

Collaborator

National Cancer Institute (NCI) (NIH)

439

Enrollment

107

Locations

Arms

Duration (Months)

4.1

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Zoledronate plus calcium and vitamin D may prevent bone loss in patients receiving adjuvant chemotherapy for breast cancer. It is not yet known which regimen is more effective in preventing bone loss.

PURPOSE: This randomized phase III trial is comparing two regimens of zoledronate plus calcium and vitamin D to see how well they work in preventing bone loss in women who are receiving adjuvant chemotherapy for breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Osteoporosis	Dietary Supplement: calcium salts Dietary Supplement: cholecalciferol Drug: zoledronic acid	Phase 3

Detailed Description

OBJECTIVES:

Compare the bone mineral density in the lumbar spine after 12 and 36 months of therapy with zoledronate, calcium, and cholecalciferol (vitamin D) in women with breast cancer receiving adjuvant chemotherapy.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to intent to treat with tamoxifen (yes vs no) and node status (negative vs positive vs unknown [for patients receiving neoadjuvant therapy]). Patients are randomized to 1 of 2 treatment arms.

Arm I: Beginning on the first day of adjuvant chemotherapy (or within 3 months after the first day), patients receive zoledronate IV over at least 15 minutes once every 3 months during months 1-24 and oral calcium and oral cholecalciferol (vitamin D) daily during months 1-36.
Arm II: Beginning on the first day of adjuvant chemotherapy (or within 3 months after the first day), patients receive oral calcium and oral vitamin D daily during months 1-36 and zoledronate IV over at least 15 minutes once every 3 months during months 13-36.

PROJECTED ACCRUAL: Approximately 400 patients (200 per treatment arm) will be accrued for this study within 24 months.

Study Design

Study Type:

Interventional

Actual Enrollment :

439 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Supportive Care

Official Title:

Phase III Trial of Intravenous Zoledronic Acid (Zometa) in the Prevention of Bone Loss in Localized Breast Cancer Patients With Chemotherapy-Induced Ovarian Failure

Study Start Date :

Dec 1, 2001

Actual Primary Completion Date :

Mar 1, 2007

Actual Study Completion Date :

Feb 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Zoledronic acid initial tx Zoledronic acid + calcium + Vit D for 2 years, followed by Calcium + vit D for 1 year	Dietary Supplement: calcium salts 1000 mg PO per day Dietary Supplement: cholecalciferol 400 IU PO per day Other Names: Vitamin D Drug: zoledronic acid 4 mg IV infusion q 3 months, months 1-24 in Zoledronic acid initial tx arm and months 13-36 in calcium + vit D initial tx arm Other Names: Zometa
Experimental: Calcium + Vit D initial Tx Calcium + vitamin D for 1 year followed by zoledronic acid + calcium + vit D for 2 years	Dietary Supplement: calcium salts 1000 mg PO per day Dietary Supplement: cholecalciferol 400 IU PO per day Other Names: Vitamin D Drug: zoledronic acid 4 mg IV infusion q 3 months, months 1-24 in Zoledronic acid initial tx arm and months 13-36 in calcium + vit D initial tx arm Other Names: Zometa

Arm

Intervention/Treatment

Experimental: Zoledronic acid initial tx

Zoledronic acid + calcium + Vit D for 2 years, followed by Calcium + vit D for 1 year

Dietary Supplement: calcium salts

1000 mg PO per day

Dietary Supplement: cholecalciferol

400 IU PO per day

Other Names:

Vitamin D

Drug: zoledronic acid

4 mg IV infusion q 3 months, months 1-24 in Zoledronic acid initial tx arm and months 13-36 in calcium + vit D initial tx arm

Other Names:

Zometa

Experimental: Calcium + Vit D initial Tx

Calcium + vitamin D for 1 year followed by zoledronic acid + calcium + vit D for 2 years

Dietary Supplement: calcium salts

1000 mg PO per day

Dietary Supplement: cholecalciferol

400 IU PO per day

Other Names:

Vitamin D

Drug: zoledronic acid

4 mg IV infusion q 3 months, months 1-24 in Zoledronic acid initial tx arm and months 13-36 in calcium + vit D initial tx arm

Other Names:

Zometa

Outcome Measures

Primary Outcome Measures

Bone mineral density in the lumbar spine [12 months from randomization]

Secondary Outcome Measures

Bone mineral density in the lumbar spine [36 months post randomization]

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed adenocarcinoma of the breast by fine needle aspirate, biopsy (tru-cut, core, stereotactic), lumpectomy, or modified radical mastectomy
Stage I-III (any T, any N, M0)
Stage IV due solely to supraclavicular node involvement allowed
Plan to use adjuvant chemotherapy* with or without adjuvant endocrine therapy*
Subsequent adjuvant hormonal therapy with an aromatase inhibitor allowed in women rendered postmenopausal by adjuvant chemotherapy NOTE: *Must be specified prior to study entry
Hormone receptor status:
Not specified

PATIENT CHARACTERISTICS:

Age:

40 and over

Sex:

Female

Menopausal status:

See Disease Characteristics
Premenopausal, defined as actively menstruating or last menstrual period occurred within 6 months prior to study entry
Prior hysterectomy without bilateral oophorectomy and estradiol and follicle-stimulating hormone within premenopausal range prior to the initiation of chemotherapy allowed

Performance status:

Not specified

Life expectancy:

Not specified

Hematopoietic:

Not specified

Hepatic:

Not specified

Renal:

Not specified

Other:

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

Not specified

Chemotherapy:

See Disease Characteristics
No more than 3 months since prior adjuvant chemotherapy

Endocrine therapy:

See Disease Characteristics

Radiotherapy:

Not specified

Surgery:

See Disease Characteristics
See Menopausal status

Other:

No other concurrent bisphosphonates
No concurrent digoxin
No concurrent tetracycline
Concurrent neoadjuvant therapy allowed
Concurrent enrollment on therapeutic adjuvant clinical trials allowed provided the therapeutic trial does not preclude participation in this trial

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arroyo Grande Community Hospital	Arroyo Grande	California	United States	93420
2	Rebecca and John Moores UCSD Cancer Center	La Jolla	California	United States	92093-0658
3	El Camino Hospital	Mountain View	California	United States	94040
4	Naval Medical Center - San Diego	San Diego	California	United States	92134
5	Veterans Affairs Medical Center - San Diego	San Diego	California	United States	92161
6	Kent General Hospital at Bayhealth Medical Center	Dover	Delaware	United States	19901
7	Beebe Medical Center	Lewes	Delaware	United States	19958
8	CCOP - Christiana Care Health Services	Newark	Delaware	United States	19713
9	St. Francis Hospital	Wilmington	Delaware	United States	19805
10	Lombardi Comprehensive Cancer Center at Georgetown University Medical Center	Washington	District of Columbia	United States	20007
11	Washington Cancer Institute at Washington Hospital Center	Washington	District of Columbia	United States	20010
12	Sibley Memorial Hospital	Washington	District of Columbia	United States	20016
13	Michael & Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital	Fort Lauderdale	Florida	United States	33308
14	Memorial Cancer Institute at Memorial Regional Hospital	Hollywood	Florida	United States	33021
15	Ella Milbank Foshay Cancer Center at Jupiter Medical Center	Jupiter	Florida	United States	33458
16	CCOP - Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
17	Cancer Research Network, Incorporated	Plantation	Florida	United States	33324
18	Cleveland Clinic Florida - Weston	Weston	Florida	United States	33331
19	St. Joseph Medical Center	Bloomington	Illinois	United States	61701
20	Graham Hospital	Canton	Illinois	United States	61520
21	Memorial Hospital	Carthage	Illinois	United States	62321
22	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60637-1470
23	Eureka Community Hospital	Eureka	Illinois	United States	61530
24	Galesburg Clinic	Galesburg	Illinois	United States	61401
25	Galesburg Cottage Hospital	Galesburg	Illinois	United States	61401
26	InterCommunity Cancer Center of Western Illinois	Galesburg	Illinois	United States	61401
27	Mason District Hospital	Havana	Illinois	United States	62644
28	Hopedale Medical Complex	Hopedale	Illinois	United States	61747
29	Kewanee Hospital	Kewanee	Illinois	United States	61443
30	La Grange Memorial Hospital	La Grange	Illinois	United States	60525
31	McDonough District Hospital	Macomb	Illinois	United States	61455
32	BroMenn Regional Medical Center	Normal	Illinois	United States	61761
33	Community Cancer Center	Normal	Illinois	United States	61761
34	Advocate Christ Medical Center	Oak Lawn	Illinois	United States	60453-2699
35	Community Hospital of Ottawa	Ottawa	Illinois	United States	61350
36	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois	United States	61554
37	Proctor Hospital	Peoria	Illinois	United States	61614
38	CCOP - Illinois Oncology Research Association	Peoria	Illinois	United States	61615
39	Oncology/Hematology Associates of Central Illinois, P.C.	Peoria	Illinois	United States	61615
40	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
41	OSF St. Francis Medical Center	Peoria	Illinois	United States	61637
42	Illinois Valley Community Hospital	Peru	Illinois	United States	61354
43	Perry Memorial Hospital	Princeton	Illinois	United States	61356
44	St. Margaret's Hospital	Spring Valley	Illinois	United States	61362
45	Valley Cancer Center	Spring Valley	Illinois	United States	61362
46	Elkhart General Hospital	Elkhart	Indiana	United States	46515
47	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana	United States	46350
48	Suniti Medical Corporation	Merrillville	Indiana	United States	46410
49	CCOP - Northern Indiana CR Consortium	South Bend	Indiana	United States	46601
50	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
51	Saint Joseph Regional Medical Center	South Bend	Indiana	United States	46617
52	Hematology Oncology Associates of the Quad Cities	Bettendorf	Iowa	United States	52722
53	Iowa Blood and Cancer Care	Cedar Rapids	Iowa	United States	52402
54	St. Luke's Hospital	Cedar Rapids	Iowa	United States	52402
55	Mercy Regional Cancer Center at Mercy Medical Center	Cedar Rapids	Iowa	United States	52403
56	Central Maine Medical Center	Lewiston	Maine	United States	04240
57	Maine Center for Cancer Medicine and Blood Disorders - Scarborough	Scarborough	Maine	United States	04074
58	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland	United States	21201
59	Harry and Jeanette Weinberg Cancer Institute at Franklin Square Hospital Center	Baltimore	Maryland	United States	21237
60	Union Hospital Cancer Center at Union Hospital	Elkton MD	Maryland	United States	21921
61	Sturdy Memorial Hospital	Attleboro	Massachusetts	United States	02703
62	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
63	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
64	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
65	Faulkner Hospital	Boston	Massachusetts	United States	02130
66	Bethke Cancer Center at Emerson Hospital	Concord	Massachusetts	United States	01742
67	Lowell General Hospital	Lowell	Massachusetts	United States	01854
68	Fairview University Medical Center - University Campus	Minneapolis	Minnesota	United States	55455
69	Saint Luke's Hospital	Chesterfield	Missouri	United States	63017
70	CCOP - Kansas City	Kansas City	Missouri	United States	64131
71	Siteman Cancer Center at Barnes-Jewish Hospital	St Louis	Missouri	United States	63110
72	Missouri Baptist Cancer Center	St. Louis	Missouri	United States	63131
73	Missouri Cancer Care, P. C. - Wentzville	Wentzville	Missouri	United States	63385
74	Methodist Cancer Center at Methodist Hospital - Omaha	Omaha	Nebraska	United States	68114
75	University Medical Center of Southern Nevada	Las Vegas	Nevada	United States	89102
76	CCOP - Nevada Cancer Research Foundation	Las Vegas	Nevada	United States	89106
77	New Hampshire Oncology-Hematology, PA - Hooksett	Hooksett	New Hampshire	United States	03106
78	Lakes Region General Hospital	Laconia	New Hampshire	United States	03246
79	Elliot Regional Cancer Center	Manchester	New Hampshire	United States	03103
80	Oncology Center at St. Joseph Hospital	Nashua	New Hampshire	United States	03060
81	Jersey City Medical Center at Liberty Health	Jersey City	New Jersey	United States	07302
82	Cancer Institute of New Jersey at the Cooper University Hospital - Voorhees	Voorhees	New Jersey	United States	08043
83	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001
84	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
85	Nalitt Cancer Institute at Staten Island University Hospital	Staten Island	New York	United States	10305
86	CCOP - Hematology-Oncology Associates of Central New York	Syracuse	New York	United States	13057
87	Community General Hospital of Greater Syracuse	Syracuse	New York	United States	13215
88	Faxton Regional Cancer Center	Utica	New York	United States	13502
89	Mission Hospitals - Memorial Campus	Asheville	North Carolina	United States	28801
90	Duke Comprehensive Cancer Center	Durham	North Carolina	United States	27710
91	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina	United States	27534
92	Pardee Memorial Hospital	Hendersonville	North Carolina	United States	28791
93	Lenoir Memorial Cancer Center	Kinston	North Carolina	United States	28501
94	Moore Regional Community Hospital Comprehensive Cancer Center	Pinehurst	North Carolina	United States	28374
95	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University	Columbus	Ohio	United States	43210-1240
96	Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital	Pittsburgh	Pennsylvania	United States	15224-1791
97	Rhode Island Hospital	Providence	Rhode Island	United States	02903
98	Women and Infants Hospital of Rhode Island	Providence	Rhode Island	United States	02905
99	Miriam Hospital at Lifespan	Providence	Rhode Island	United States	02906
100	CCOP - Greenville	Greenville	South Carolina	United States	29615
101	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas	United States	75390
102	Southwestern Vermont Regional Cancer Center	Bennington	Vermont	United States	05201
103	Mountainview Medical	Berlin	Vermont	United States	05602
104	Fletcher Allen Health Care - University Health Center Campus	Burlington	Vermont	United States	05401
105	Community Cancer Center at Rutland Regional Medical Center	Rutland	Vermont	United States	05701
106	Danville Regional Medical Center	Danville	Virginia	United States	24541
107	St. Mary's Regional Cancer Center at St. Mary's Medical Center	Huntington	West Virginia	United States	25702