Continued Efficacy and Safety of Zoledronic Acid (q 4 Wks vs. q 12 Wks) in the 2nd Year of Treatment in Patients With Bone Metastases From Breast Cancer

Breast Cancer Clinical Trial

Official title:

A Prospective, Randomized, Double-blind, Stratified, Multi-center, 2-arm Trial of the Continued Efficacy and Safety of Zoledronic Acid (Every 4 Weeks vs. Every 12 Weeks) in in the 2nd Year of Treatment in Patients With Documented Bone Metastases From Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00320710
• Other study ID #: CZOL446E2352
• Status: Completed
• Phase: Phase 3
• First received: April 28, 2006
• Last updated: August 18, 2014
• Start date: February 2006
• Est. completion date: July 2013

Study information

• Verified date: August 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Clinical trial in breast cancer patients with bone metastases pretreated for approximately 1 year with a standard zoledronic acid regimen. Looking at the continued effectiveness and safety of giving zoledronic acid every 4 weeks versus every 12 weeks given over 1 year. This study is prospective, double-blind, stratified, multi-center, and two-arm.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 416
• Est. completion date: July 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Female patients = 18 years of age. Confirmed breast cancer with bone metastasis. Pretreated with Zometa®, or Aredia (pamidronate) or all sequential regimens of both, for a minimum of 9 doses;

Exclusion Criteria:

Abnormal kidney function determined by serum creatinine levels. Current active dental problems including: ongoing infection of the teeth or jawbone; current exposed bone in the mouth; and current or prior diagnosis of osteonecrosis of the jaw.

Recent (within 8 weeks) or planned dental or jaw surgery (e.g., extraction, implants).

Diagnosis of metabolic bone disease other than osteoporosis (e.g., Paget's disease of bone).

Known hypersensitivity to Zometa. Treatment with other investigational drugs within 30 days prior to randomization.

Other protocol-defined exclusion criteria may have applied.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Zoledronic acid
4mg IV
• Placebo
Placebo to zoledronic acid

Locations

Country	Name	City	State
United States	Cabrini Center for Cancer Care	Alexandria	Louisiana
United States	Pacific Cancer Medical Center, Inc.	Anaheim	California
United States	Providence Alaska Medical Center Cancer Research	Anchorage	Alaska
United States	University of Michigan Clinical Trials Office	Ann Arbor	Michigan
United States	Advanced Oncology Associates	Armonk	New York
United States	Greenbaum Cancer Center	Baltimore	Maryland
United States	St. Agnes Hospital	Baltimore	Maryland
United States	The Harry and Jeanette Weinberg Cancer Institute at Franklin	Baltimore	Maryland
United States	Barberton Citizens Hospital	Barberton	Ohio
United States	Center for Cancer & Blood Disorders	Bethesda	Maryland
United States	Alamance Regional Medical Cancer Center	Burlington	North Carolina
United States	South Bay Oncology Hematology Partners	Campbell	California
United States	Gabrail Cancer Center	Canton	Ohio
United States	Center for Cancer and Hematologic Disease	Cherry Hill	New Jersey
United States	NorthwesternUniv.Med.School/Robert H. Lurie Comp.Cancer Ctr	Chicago	Illinois
United States	M. Francisco Gonzalez, MD., FACP	Columbia	South Carolina
United States	Bay Area Cancer Research	Concord	California
United States	Northeast Oncology Associates Suite 250	Concord	North Carolina
United States	Bay Area Hospital - Pharmacy	Coos Bay	Oregon
United States	The Corvallis Clinic, P.C.	Corvallis	Oregon
United States	Denver Health Medical Center CACZ885M2301	Denver	Colorado
United States	Henry Ford Hospital Oncology	Detroit	Michigan
United States	Wayne State University	Detroit	Michigan
United States	Medical Associates Clinic, PC	Dubuque	Iowa
United States	St. Luke's Hospital and Health Network	Duluth	Minnesota
United States	Evanston Northwestern Healthcare Medical Group	Evanston	Illinois
United States	Providence Everett Medical Clinic	Everett	Washington
United States	Pacific Coast Hem/Onc	Fountain Valley	California
United States	Frederick Memorial Hospital	Frederick	Maryland
United States	Arena Oncology Associates, PC	Great Neck	New York
United States	Kentucky Lung Clinic & Kentucky Sleep Clinic	Hazard	Kentucky
United States	Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	Heritage Physicians Group Oncology	Hot Springs	Arkansas
United States	MD Anderson Cancer Center/University of Texas 1155 Herman Pressler Street	Houston	Texas
United States	Investigative Clinical Research	Indianapolis	Indiana
United States	University of Iowa Health Care	Iowa City	Iowa
United States	Jackson Oncology Associates	Jackson	Mississippi
United States	Baptist Cancer Center	Jacksonville	Florida
United States	Capitol Comprehensive Cancer Care Clinic	Jefferson City	Missouri
United States	Benedictine Hospital	Kingston	New York
United States	Wilshire Oncology Medical Group	La Verne	California
United States	Southwest Oncology Associates Ltd.	Lafayette	Louisiana
United States	Lancaster Cancer Center	Lancaster	Pennsylvania
United States	Nevada Cancer Centers 2851 North Tenaya Way	Las Vegas	Nevada
United States	Suburban Hematology-Oncology	Lawrenceville	Georgia
United States	Lexington Oncology Associates	Lexington	Kentucky
United States	Nebraska Hematology-Oncology PC	Lincoln	Nebraska
United States	Saint Barnabas Medical Center	Livingston	New Jersey
United States	Kenmar Research Institute	Los Angeles	California
United States	Ohio Cancer Specialists	Mansfield	Ohio
United States	Caritas Holy Family Hospital	Methuen	Massachusetts
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Fairview Clinical Trial Services	Minneapolis	Minnesota
United States	Univ. of Minnesota Cancer Center 420 Delaware St.	Minneapolis	Minnesota
United States	Edward Cancer Center	Naperville	Illinois
United States	Cancer Care Center	New Albany	Indiana
United States	Pasco Hernando Oncology	New Port Richey	Florida
United States	Beth Israel Medical Center	New York	New York
United States	Columbia Presbyterian Medical Center	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	North Valley Hematology/Oncology Providence Holy Cross Medical	Northridge	California
United States	Eastern Connecticut Hematology & Oncology Associates	Norwich	Connecticut
United States	Medical Oncology Care Associates	Orange	California
United States	Ventura County Hematology and Oncology	Oxnard	California
United States	U of Pittsburgh Cancer Institute Magee-Womens Hospital	Pittsburgh	Pennsylvania
United States	The Office of Dr. Elizabeth Tan-Chiu, MD PA	Planatation	Florida
United States	The Office of Dr. Swarna Chanduri, MD	Pomona	California
United States	Access Clinical Research	Rancho Mirage	California
United States	Cancer and Blood of the Desert	Rancho Mirage	California
United States	Hubert H. Humphrey Cancer Center	Robbinsdale	Minnesota
United States	Jmaes P. Wilmot Cancer Center	Rochester	New York
United States	University of California Davis Cancer Center	Sacramento	California
United States	Cancer Centers of South Texas	San Antonio	Texas
United States	Guthrie Cancer Center	Sayre	Pennsylvania
United States	Seattle Cancer Care Alliance Seattle Cancer Care Alliance	Seattle	Washington
United States	Siouxland Hematology-Oncology Associates LLP	Sioux City	Iowa
United States	Midwest Cancer Research Group	Skokie	Illinois
United States	Somerset Hematology Oncology Associates	Somerset	New Jersey
United States	Rockwood Clinic Rockwood Clinic, PS	Spokane	Washington
United States	The Center for Chest Care	Springdale	Arkansas
United States	Oncology Care Associates, PLLC	St. Joseph	Michigan
United States	The Center for Cancer Care and Research	St. Louis	Missouri
United States	Santee Hematology/Oncology	Sumter	South Carolina
United States	University of California at Los Angeles	Sylmar	California
United States	Associated Physicians & Surgeons Clinic	Terre Haute	Indiana
United States	Cotton O'Neil Oncology Clinic	Topeka	Kansas
United States	Georgetown University/Lombardi Cancer Center	Washington	District of Columbia
United States	Washington Hospital Center	Washington	District of Columbia
United States	Hematology/Oncology Consultants Inc.	West Worthington	Ohio
United States	Cancer Center of Kansas	Witchita	Kansas
United States	Trilogy Cancer Care	Wooster	Ohio
United States	Mainline Oncology Hematology Assoc.	Wynnewood	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Patients Who Experienced at Least One Skeletal Related Event (SRE)	An SRE was defined as a pathologic fracture (vertebral and non-vertebral), spinal cord compression, radiation to bone or surgery to bone.	52 weeks	No
Secondary	Time to First SRE	An SRE was defined as a pathologic bone fracture (vertebral and non-vertebral), spinal cord compression, radiation to bone, or surgery to bone. The time to first individual SRE was defined as the date of randomization to the date of first occurrence of any SRE.	52 weeks	No
Secondary	Time to First Individual Type of SRE	Types of SREs analyzed were pathologic fractures (vertebral and non-vertebral), spinal cord compression, radiation to bone and surgery to bone. The time to first indvidual SRE was defined as the date of randomization to the date of the first occurrence of any individual SRE.	52 weeks	No
Secondary	Change From Baseline in Mean Composite Brief Pain Inventory (BPI) Score	Participants completed a BPI short form which is a 9 item self-administered questionnaire used to evaluate the severity of a participant's pain and the impact of this pain on the participant's daily functioning. The participant rates his or her worst, least, average, and current pain intensity, lists current treatments and perceived effectiveness, and rates the degree that pain interferes with general activity, mood, walking ability, normal work, relations with other persons, sleep, and enjoyment of life on a 10 point scale. The BPI composite score, which was calculated as the average of items 3, 4, 5 and 6 (worst pain, least pain, average pain and pain right now), ranged from 0 (best possible outcome, no pain) to 10 (worst possible outcome, pain as bad as you can imagine). A positive change from baseline indicates worsening.	baseline, 52 weeks	No
Secondary	Change From Baseline in Mean Analgesic Score	The analgesic score indicates the types of pain medication used. The scores range as follows: 0 = none medication; 1 = minor analgesics (aspirin, NSAID, acetaminophen, propoxyphene, etc.); 2 = Tranquilizers, antidepressants, muscle relaxants, and steroids; 3 = Mild narcotics (oxycodone, meperidine, codeine, etc.); and 4 = Strong narcotics (morphine, hydromorphone, etc.). A positive change from baseline indicates worsening.	baseline, 52 weeks	No
Secondary	Change From Baseline in Urinary N-telopeptide / Creatinine Ratio	Urine samples were collected to obtain n-telopeptide and creatinine values.	baseline, 48 weeks	No
Secondary	Change From Baseline in Serum Bone Specific Alkaline Phosphatase	Serum samples were collected to obtain bone specific alkaline phosphatase values.	baseline, 48 weeks	No
Secondary	Skeletal Morbidity Rate	An SMR for a patient was defined as the "number of occurrences" of any (or a particular) SRE allowing for only 1 event in any 3-week interval, divided by the "time at risk" in years. The "number of occurrences" and the "time at risk" were counts of SRE and the time from the randomization date. Counting began from randomization in the way that every counted event was followed by a 20-day period during which no SRE was counted, nor was the time counted as "at risk". For example, if a patient had 1 SRE during the study, the "time at risk" was calculated as the total number of days in the study minus the 20-day follow-up period for that SRE. If a patient had no SRE events, the entire study period was counted as "time at risk". This SMR calculation method had the advantage of avoiding multiple counts of possibly interdependent SREs (e.g. having 1 fracture increases the probability of having a subsequent SRE).	52 weeks	No

External Links

•   Breast Cancer