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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00022087
• Other study ID #: CALGB-79809
• Secondary ID: U10CA031946CALGB
• Status: Completed
• Phase: Phase 3
• First received: August 10, 2001
• Last updated: July 15, 2016
• Start date: December 2001
• Est. completion date: February 2009

Study information

• Verified date: July 2016
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 439
• Est. completion date: February 2009
• Est. primary completion date: March 2007
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 40 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Osteoporosis

Intervention

Dietary Supplement:
• calcium salts
1000 mg PO per day
• cholecalciferol
400 IU PO per day

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

Locations

Country	Name	City	State
United States	Arroyo Grande Community Hospital	Arroyo Grande	California
United States	Mission Hospitals - Memorial Campus	Asheville	North Carolina
United States	Sturdy Memorial Hospital	Attleboro	Massachusetts
United States	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland
United States	Harry and Jeanette Weinberg Cancer Institute at Franklin Square Hospital Center	Baltimore	Maryland
United States	Southwestern Vermont Regional Cancer Center	Bennington	Vermont
United States	Mountainview Medical	Berlin	Vermont
United States	Hematology Oncology Associates of the Quad Cities	Bettendorf	Iowa
United States	St. Joseph Medical Center	Bloomington	Illinois
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts
United States	Faulkner Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Fletcher Allen Health Care - University Health Center Campus	Burlington	Vermont
United States	Graham Hospital	Canton	Illinois
United States	Memorial Hospital	Carthage	Illinois
United States	Iowa Blood and Cancer Care	Cedar Rapids	Iowa
United States	Mercy Regional Cancer Center at Mercy Medical Center	Cedar Rapids	Iowa
United States	St. Luke's Hospital	Cedar Rapids	Iowa
United States	Saint Luke's Hospital	Chesterfield	Missouri
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University	Columbus	Ohio
United States	Bethke Cancer Center at Emerson Hospital	Concord	Massachusetts
United States	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas
United States	Danville Regional Medical Center	Danville	Virginia
United States	Kent General Hospital at Bayhealth Medical Center	Dover	Delaware
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Union Hospital Cancer Center at Union Hospital	Elkton MD	Maryland
United States	Eureka Community Hospital	Eureka	Illinois
United States	Michael & Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital	Fort Lauderdale	Florida
United States	Galesburg Clinic	Galesburg	Illinois
United States	Galesburg Cottage Hospital	Galesburg	Illinois
United States	InterCommunity Cancer Center of Western Illinois	Galesburg	Illinois
United States	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina
United States	CCOP - Greenville	Greenville	South Carolina
United States	Mason District Hospital	Havana	Illinois
United States	Pardee Memorial Hospital	Hendersonville	North Carolina
United States	Memorial Cancer Institute at Memorial Regional Hospital	Hollywood	Florida
United States	New Hampshire Oncology-Hematology, PA - Hooksett	Hooksett	New Hampshire
United States	Hopedale Medical Complex	Hopedale	Illinois
United States	St. Mary's Regional Cancer Center at St. Mary's Medical Center	Huntington	West Virginia
United States	Jersey City Medical Center at Liberty Health	Jersey City	New Jersey
United States	Ella Milbank Foshay Cancer Center at Jupiter Medical Center	Jupiter	Florida
United States	CCOP - Kansas City	Kansas City	Missouri
United States	Kewanee Hospital	Kewanee	Illinois
United States	Lenoir Memorial Cancer Center	Kinston	North Carolina
United States	La Grange Memorial Hospital	La Grange	Illinois
United States	Rebecca and John Moores UCSD Cancer Center	La Jolla	California
United States	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana
United States	Lakes Region General Hospital	Laconia	New Hampshire
United States	CCOP - Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Beebe Medical Center	Lewes	Delaware
United States	Central Maine Medical Center	Lewiston	Maine
United States	Lowell General Hospital	Lowell	Massachusetts
United States	McDonough District Hospital	Macomb	Illinois
United States	Elliot Regional Cancer Center	Manchester	New Hampshire
United States	Suniti Medical Corporation	Merrillville	Indiana
United States	CCOP - Mount Sinai Medical Center	Miami Beach	Florida
United States	Fairview University Medical Center - University Campus	Minneapolis	Minnesota
United States	El Camino Hospital	Mountain View	California
United States	Oncology Center at St. Joseph Hospital	Nashua	New Hampshire
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	BroMenn Regional Medical Center	Normal	Illinois
United States	Community Cancer Center	Normal	Illinois
United States	Advocate Christ Medical Center	Oak Lawn	Illinois
United States	Methodist Cancer Center at Methodist Hospital - Omaha	Omaha	Nebraska
United States	Community Hospital of Ottawa	Ottawa	Illinois
United States	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Oncology/Hematology Associates of Central Illinois, P.C.	Peoria	Illinois
United States	OSF St. Francis Medical Center	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois Valley Community Hospital	Peru	Illinois
United States	Moore Regional Community Hospital Comprehensive Cancer Center	Pinehurst	North Carolina
United States	Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital	Pittsburgh	Pennsylvania
United States	Cancer Research Network, Incorporated	Plantation	Florida
United States	Perry Memorial Hospital	Princeton	Illinois
United States	Miriam Hospital at Lifespan	Providence	Rhode Island
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Women and Infants Hospital of Rhode Island	Providence	Rhode Island
United States	Community Cancer Center at Rutland Regional Medical Center	Rutland	Vermont
United States	Naval Medical Center - San Diego	San Diego	California
United States	Veterans Affairs Medical Center - San Diego	San Diego	California
United States	Maine Center for Cancer Medicine and Blood Disorders - Scarborough	Scarborough	Maine
United States	CCOP - Northern Indiana CR Consortium	South Bend	Indiana
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Saint Joseph Regional Medical Center	South Bend	Indiana
United States	St. Margaret's Hospital	Spring Valley	Illinois
United States	Valley Cancer Center	Spring Valley	Illinois
United States	Siteman Cancer Center at Barnes-Jewish Hospital	St Louis	Missouri
United States	Missouri Baptist Cancer Center	St. Louis	Missouri
United States	Nalitt Cancer Institute at Staten Island University Hospital	Staten Island	New York
United States	CCOP - Hematology-Oncology Associates of Central New York	Syracuse	New York
United States	Community General Hospital of Greater Syracuse	Syracuse	New York
United States	Faxton Regional Cancer Center	Utica	New York
United States	Cancer Institute of New Jersey at the Cooper University Hospital - Voorhees	Voorhees	New Jersey
United States	Lombardi Comprehensive Cancer Center at Georgetown University Medical Center	Washington	District of Columbia
United States	Sibley Memorial Hospital	Washington	District of Columbia
United States	Washington Cancer Institute at Washington Hospital Center	Washington	District of Columbia
United States	Missouri Cancer Care, P. C. - Wentzville	Wentzville	Missouri
United States	Cleveland Clinic Florida - Weston	Weston	Florida
United States	St. Francis Hospital	Wilmington	Delaware

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Bone mineral density in the lumbar spine		12 months from randomization	No
Secondary	Bone mineral density in the lumbar spine		36 months post randomization	No