Clinical trial NCT00022087: Zoledronate, Calcium, and Vitamin D in Preventing Bone Loss in Women Receiving Adjuvant Chemotherapy for Breast Cancer
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Osteoporosis
Keywords: osteoporosis
stage I breast cancer
stage II breast cancer
stage IV breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 439
Sex: FEMALE
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Bone mineral density in the lumbar spine
timeFrame: 12 months from randomization
Secondary outcomes:
measure: Bone mineral density in the lumbar spine
timeFrame: 36 months post randomization
Other outcomes:
Locations:
city: Arroyo Grande
country: United States
facility: Arroyo Grande Community Hospital
state: California
city: La Jolla
country: United States
facility: Rebecca and John Moores UCSD Cancer Center
state: California
city: Mountain View
country: United States
facility: El Camino Hospital
state: California
city: San Diego
country: United States
facility: Naval Medical Center - San Diego
state: California
city: San Diego
country: United States
facility: Veterans Affairs Medical Center - San Diego
state: California
city: Dover
country: United States
facility: Kent General Hospital at Bayhealth Medical Center
state: Delaware
city: Lewes
country: United States
facility: Beebe Medical Center
state: Delaware
city: Newark
country: United States
facility: CCOP - Christiana Care Health Services
state: Delaware
city: Wilmington
country: United States
facility: St. Francis Hospital
state: Delaware
city: Washington
country: United States
facility: Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
state: District of Columbia
city: Washington
country: United States
facility: Washington Cancer Institute at Washington Hospital Center
state: District of Columbia
city: Washington
country: United States
facility: Sibley Memorial Hospital
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Michael & Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital
state: Florida
city: Hollywood
country: United States
facility: Memorial Cancer Institute at Memorial Regional Hospital
state: Florida
city: Jupiter
country: United States
facility: Ella Milbank Foshay Cancer Center at Jupiter Medical Center
state: Florida
city: Miami Beach
country: United States
facility: CCOP - Mount Sinai Medical Center
state: Florida
city: Plantation
country: United States
facility: Cancer Research Network, Incorporated
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida - Weston
state: Florida
city: Bloomington
country: United States
facility: St. Joseph Medical Center
state: Illinois
city: Canton
country: United States
facility: Graham Hospital
state: Illinois
city: Carthage
country: United States
facility: Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Eureka
country: United States
facility: Eureka Community Hospital
state: Illinois
city: Galesburg
country: United States
facility: Galesburg Clinic
state: Illinois
city: Galesburg
country: United States
facility: Galesburg Cottage Hospital
state: Illinois
city: Galesburg
country: United States
facility: InterCommunity Cancer Center of Western Illinois
state: Illinois
city: Havana
country: United States
facility: Mason District Hospital
state: Illinois
city: Hopedale
country: United States
facility: Hopedale Medical Complex
state: Illinois
city: Kewanee
country: United States
facility: Kewanee Hospital
state: Illinois
city: La Grange
country: United States
facility: La Grange Memorial Hospital
state: Illinois
city: Macomb
country: United States
facility: McDonough District Hospital
state: Illinois
city: Normal
country: United States
facility: BroMenn Regional Medical Center
state: Illinois
city: Normal
country: United States
facility: Community Cancer Center
state: Illinois
city: Oak Lawn
country: United States
facility: Advocate Christ Medical Center
state: Illinois
city: Ottawa
country: United States
facility: Community Hospital of Ottawa
state: Illinois
city: Pekin
country: United States
facility: Cancer Treatment Center at Pekin Hospital
state: Illinois
city: Peoria
country: United States
facility: Proctor Hospital
state: Illinois
city: Peoria
country: United States
facility: CCOP - Illinois Oncology Research Association
state: Illinois
city: Peoria
country: United States
facility: Oncology/Hematology Associates of Central Illinois, P.C.
state: Illinois
city: Peoria
country: United States
facility: Methodist Medical Center of Illinois
state: Illinois
city: Peoria
country: United States
facility: OSF St. Francis Medical Center
state: Illinois
city: Peru
country: United States
facility: Illinois Valley Community Hospital
state: Illinois
city: Princeton
country: United States
facility: Perry Memorial Hospital
state: Illinois
city: Spring Valley
country: United States
facility: St. Margaret's Hospital
state: Illinois
city: Spring Valley
country: United States
facility: Valley Cancer Center
state: Illinois
city: Elkhart
country: United States
facility: Elkhart General Hospital
state: Indiana
city: La Porte
country: United States
facility: Center for Cancer Therapy at LaPorte Hospital and Health Services
state: Indiana
city: Merrillville
country: United States
facility: Suniti Medical Corporation
state: Indiana
city: South Bend
country: United States
facility: CCOP - Northern Indiana CR Consortium
state: Indiana
city: South Bend
country: United States
facility: Memorial Hospital of South Bend
state: Indiana
city: South Bend
country: United States
facility: Saint Joseph Regional Medical Center
state: Indiana
city: Bettendorf
country: United States
facility: Hematology Oncology Associates of the Quad Cities
state: Iowa
city: Cedar Rapids
country: United States
facility: Iowa Blood and Cancer Care
state: Iowa
city: Cedar Rapids
country: United States
facility: St. Luke's Hospital
state: Iowa
city: Cedar Rapids
country: United States
facility: Mercy Regional Cancer Center at Mercy Medical Center
state: Iowa
city: Lewiston
country: United States
facility: Central Maine Medical Center
state: Maine
city: Scarborough
country: United States
facility: Maine Center for Cancer Medicine and Blood Disorders - Scarborough
state: Maine
city: Baltimore
country: United States
facility: Greenebaum Cancer Center at University of Maryland Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Harry and Jeanette Weinberg Cancer Institute at Franklin Square Hospital Center
state: Maryland
city: Elkton MD
country: United States
facility: Union Hospital Cancer Center at Union Hospital
state: Maryland
city: Attleboro
country: United States
facility: Sturdy Memorial Hospital
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Faulkner Hospital
state: Massachusetts
city: Concord
country: United States
facility: Bethke Cancer Center at Emerson Hospital
state: Massachusetts
city: Lowell
country: United States
facility: Lowell General Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: Fairview University Medical Center - University Campus
state: Minnesota
city: Chesterfield
country: United States
facility: Saint Luke's Hospital
state: Missouri
city: Kansas City
country: United States
facility: CCOP - Kansas City
state: Missouri
city: St Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital
state: Missouri
city: St. Louis
country: United States
facility: Missouri Baptist Cancer Center
state: Missouri
city: Wentzville
country: United States
facility: Missouri Cancer Care, P. C. - Wentzville
state: Missouri
city: Omaha
country: United States
facility: Methodist Cancer Center at Methodist Hospital - Omaha
state: Nebraska
city: Las Vegas
country: United States
facility: University Medical Center of Southern Nevada
state: Nevada
city: Las Vegas
country: United States
facility: CCOP - Nevada Cancer Research Foundation
state: Nevada
city: Hooksett
country: United States
facility: New Hampshire Oncology-Hematology, PA - Hooksett
state: New Hampshire
city: Laconia
country: United States
facility: Lakes Region General Hospital
state: New Hampshire
city: Manchester
country: United States
facility: Elliot Regional Cancer Center
state: New Hampshire
city: Nashua
country: United States
facility: Oncology Center at St. Joseph Hospital
state: New Hampshire
city: Jersey City
country: United States
facility: Jersey City Medical Center at Liberty Health
state: New Jersey
city: Voorhees
country: United States
facility: Cancer Institute of New Jersey at the Cooper University Hospital - Voorhees
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Staten Island
country: United States
facility: Nalitt Cancer Institute at Staten Island University Hospital
state: New York
city: Syracuse
country: United States
facility: CCOP - Hematology-Oncology Associates of Central New York
state: New York
city: Syracuse
country: United States
facility: Community General Hospital of Greater Syracuse
state: New York
city: Utica
country: United States
facility: Faxton Regional Cancer Center
state: New York
city: Asheville
country: United States
facility: Mission Hospitals - Memorial Campus
state: North Carolina
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
city: Goldsboro
country: United States
facility: Wayne Memorial Hospital, Incorporated
state: North Carolina
city: Hendersonville
country: United States
facility: Pardee Memorial Hospital
state: North Carolina
city: Kinston
country: United States
facility: Lenoir Memorial Cancer Center
state: North Carolina
city: Pinehurst
country: United States
facility: Moore Regional Community Hospital Comprehensive Cancer Center
state: North Carolina
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University
state: Ohio
city: Pittsburgh
country: United States
facility: Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Providence
country: United States
facility: Women and Infants Hospital of Rhode Island
state: Rhode Island
city: Providence
country: United States
facility: Miriam Hospital at Lifespan
state: Rhode Island
city: Greenville
country: United States
facility: CCOP - Greenville
state: South Carolina
city: Dallas
country: United States
facility: Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
state: Texas
city: Bennington
country: United States
facility: Southwestern Vermont Regional Cancer Center
state: Vermont
city: Berlin
country: United States
facility: Mountainview Medical
state: Vermont
city: Burlington
country: United States
facility: Fletcher Allen Health Care - University Health Center Campus
state: Vermont
city: Rutland
country: United States
facility: Community Cancer Center at Rutland Regional Medical Center
state: Vermont
city: Danville
country: United States
facility: Danville Regional Medical Center
state: Virginia
city: Huntington
country: United States
facility: St. Mary's Regional Cancer Center at St. Mary's Medical Center
state: West Virginia
Study officials:
affiliation: Ohio State University Comprehensive Cancer Center
name: Charles L. Shapiro, MD
role: STUDY_CHAIR
References:
citation: Shapiro CL, Halabi S, Gibson G, et al.: Effect of zoledronic acid (ZA) on bone mineral density (BMD) in premenopausal women who develop ovarian failure (OF) due to adjuvant chemotherapy (AdC): first results from CALGB trial 79809. [Abstract] J Clin Oncol 26 (Suppl 15): A-512, 2008.