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
- Registration Number
- NCT00320710
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 416
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;
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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Zoledronic acid q 12 weeks Placebo Participants received 4 mg zoledronic acid IV q 12 weeks and received placebo to Zometa IV at the 4 week intervals between the q 12 week zoledronic acid infusions in order to maintain the blind. Placebo / zoledronic acid Placebo Participants randomized to this arm received placebo but the arm was later dropped and participants in this arm were swithced to the zoledronic acid q 4 weeks according to a study amendment. Zoledronic acid every (q) 4 weeks Zoledronic acid Participants received 4mg of zoledronic acid intravenously (IV) infusion q 4 weeks. Zoledronic acid q 12 weeks Zoledronic acid Participants received 4 mg zoledronic acid IV q 12 weeks and received placebo to Zometa IV at the 4 week intervals between the q 12 week zoledronic acid infusions in order to maintain the blind. Placebo / zoledronic acid Zoledronic acid Participants randomized to this arm received placebo but the arm was later dropped and participants in this arm were swithced to the zoledronic acid q 4 weeks according to a study amendment.
- Primary Outcome Measures
Name Time Method Proportion of Patients Who Experienced at Least One Skeletal Related Event (SRE) 52 weeks An SRE was defined as a pathologic fracture (vertebral and non-vertebral), spinal cord compression, radiation to bone or surgery to bone.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Mean Composite Brief Pain Inventory (BPI) Score baseline, 52 weeks 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.
Time to First Individual Type of SRE 52 weeks 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.
Change From Baseline in Urinary N-telopeptide / Creatinine Ratio baseline, 48 weeks Urine samples were collected to obtain n-telopeptide and creatinine values.
Change From Baseline in Serum Bone Specific Alkaline Phosphatase baseline, 48 weeks Serum samples were collected to obtain bone specific alkaline phosphatase values.
Skeletal Morbidity Rate 52 weeks 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).
Change From Baseline in Mean Analgesic Score baseline, 52 weeks 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.
Time to First SRE 52 weeks 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.
Trial Locations
- Locations (92)
Greenbaum Cancer Center
🇺🇸Baltimore, Maryland, United States
U of Pittsburgh Cancer Institute Magee-Womens Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Frederick Memorial Hospital
🇺🇸Frederick, Maryland, United States
Heritage Physicians Group Oncology
🇺🇸Hot Springs, Arkansas, United States
Providence Alaska Medical Center Cancer Research
🇺🇸Anchorage, Alaska, United States
The Center for Chest Care
🇺🇸Springdale, Arkansas, United States
Pacific Cancer Medical Center, Inc.
🇺🇸Anaheim, California, United States
South Bay Oncology Hematology Partners
🇺🇸Campbell, California, United States
Bay Area Cancer Research
🇺🇸Concord, California, United States
Pacific Coast Hem/Onc
🇺🇸Fountain Valley, California, United States
Kenmar Research Institute
🇺🇸Los Angeles, California, United States
Wilshire Oncology Medical Group
🇺🇸La Verne, California, United States
North Valley Hematology/Oncology Providence Holy Cross Medical
🇺🇸Northridge, California, United States
Medical Oncology Care Associates
🇺🇸Orange, California, United States
Ventura County Hematology and Oncology
🇺🇸Oxnard, California, United States
The Office of Dr. Swarna Chanduri, MD
🇺🇸Pomona, California, United States
University of California at Los Angeles
🇺🇸Sylmar, California, United States
Cancer and Blood of the Desert
🇺🇸Rancho Mirage, California, United States
Access Clinical Research
🇺🇸Rancho Mirage, California, United States
Eastern Connecticut Hematology & Oncology Associates
🇺🇸Norwich, Connecticut, United States
Georgetown University/Lombardi Cancer Center
🇺🇸Washington, District of Columbia, United States
Washington Hospital Center
🇺🇸Washington, District of Columbia, United States
Baptist Cancer Center
🇺🇸Jacksonville, Florida, United States
The Office of Dr. Elizabeth Tan-Chiu, MD PA
🇺🇸Planatation, Florida, United States
Pasco Hernando Oncology
🇺🇸New Port Richey, Florida, United States
Suburban Hematology-Oncology
🇺🇸Lawrenceville, Georgia, United States
NorthwesternUniv.Med.School/Robert H. Lurie Comp.Cancer Ctr
🇺🇸Chicago, Illinois, United States
Edward Cancer Center
🇺🇸Naperville, Illinois, United States
Evanston Northwestern Healthcare Medical Group
🇺🇸Evanston, Illinois, United States
Midwest Cancer Research Group
🇺🇸Skokie, Illinois, United States
Associated Physicians & Surgeons Clinic
🇺🇸Terre Haute, Indiana, United States
Cancer Care Center
🇺🇸New Albany, Indiana, United States
Medical Associates Clinic, PC
🇺🇸Dubuque, Iowa, United States
Siouxland Hematology-Oncology Associates LLP
🇺🇸Sioux City, Iowa, United States
University of Iowa Health Care
🇺🇸Iowa City, Iowa, United States
Cotton O'Neil Oncology Clinic
🇺🇸Topeka, Kansas, United States
Cancer Center of Kansas
🇺🇸Witchita, Kansas, United States
Southwest Oncology Associates Ltd.
🇺🇸Lafayette, Louisiana, United States
Kentucky Lung Clinic & Kentucky Sleep Clinic
🇺🇸Hazard, Kentucky, United States
Cabrini Center for Cancer Care
🇺🇸Alexandria, Louisiana, United States
Lexington Oncology Associates
🇺🇸Lexington, Kentucky, United States
St. Agnes Hospital
🇺🇸Baltimore, Maryland, United States
The Harry and Jeanette Weinberg Cancer Institute at Franklin
🇺🇸Baltimore, Maryland, United States
Caritas Holy Family Hospital
🇺🇸Methuen, Massachusetts, United States
St. Luke's Hospital and Health Network
🇺🇸Duluth, Minnesota, United States
Oncology Care Associates, PLLC
🇺🇸St. Joseph, Michigan, United States
Jackson Oncology Associates
🇺🇸Jackson, Mississippi, United States
Hubert H. Humphrey Cancer Center
🇺🇸Robbinsdale, Minnesota, United States
Capitol Comprehensive Cancer Care Clinic
🇺🇸Jefferson City, Missouri, United States
The Center for Cancer Care and Research
🇺🇸St. Louis, Missouri, United States
Nebraska Hematology-Oncology PC
🇺🇸Lincoln, Nebraska, United States
Center for Cancer and Hematologic Disease
🇺🇸Cherry Hill, New Jersey, United States
Somerset Hematology Oncology Associates
🇺🇸Somerset, New Jersey, United States
Advanced Oncology Associates
🇺🇸Armonk, New York, United States
Arena Oncology Associates, PC
🇺🇸Great Neck, New York, United States
Benedictine Hospital
🇺🇸Kingston, New York, United States
Beth Israel Medical Center
🇺🇸New York, New York, United States
Columbia Presbyterian Medical Center
🇺🇸New York, New York, United States
Jmaes P. Wilmot Cancer Center
🇺🇸Rochester, New York, United States
Alamance Regional Medical Cancer Center
🇺🇸Burlington, North Carolina, United States
Barberton Citizens Hospital
🇺🇸Barberton, Ohio, United States
Northeast Oncology Associates Suite 250
🇺🇸Concord, North Carolina, United States
Trilogy Cancer Care
🇺🇸Wooster, Ohio, United States
Gabrail Cancer Center
🇺🇸Canton, Ohio, United States
Hematology/Oncology Consultants Inc.
🇺🇸West Worthington, Ohio, United States
Ohio Cancer Specialists
🇺🇸Mansfield, Ohio, United States
Bay Area Hospital - Pharmacy
🇺🇸Coos Bay, Oregon, United States
The Corvallis Clinic, P.C.
🇺🇸Corvallis, Oregon, United States
Milton S Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Lancaster Cancer Center
🇺🇸Lancaster, Pennsylvania, United States
Guthrie Cancer Center
🇺🇸Sayre, Pennsylvania, United States
Mainline Oncology Hematology Assoc.
🇺🇸Wynnewood, Pennsylvania, United States
M. Francisco Gonzalez, MD., FACP
🇺🇸Columbia, South Carolina, United States
MD Anderson Cancer Center/University of Texas 1155 Herman Pressler Street
🇺🇸Houston, Texas, United States
Santee Hematology/Oncology
🇺🇸Sumter, South Carolina, United States
Seattle Cancer Care Alliance Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Providence Everett Medical Clinic
🇺🇸Everett, Washington, United States
Rockwood Clinic Rockwood Clinic, PS
🇺🇸Spokane, Washington, United States
Saint Barnabas Medical Center
🇺🇸Livingston, New Jersey, United States
Denver Health Medical Center CACZ885M2301
🇺🇸Denver, Colorado, United States
Investigative Clinical Research
🇺🇸Indianapolis, Indiana, United States
Center for Cancer & Blood Disorders
🇺🇸Bethesda, Maryland, United States
Wayne State University
🇺🇸Detroit, Michigan, United States
Henry Ford Hospital Oncology
🇺🇸Detroit, Michigan, United States
Fairview Clinical Trial Services
🇺🇸Minneapolis, Minnesota, United States
Univ. of Minnesota Cancer Center 420 Delaware St.
🇺🇸Minneapolis, Minnesota, United States
Nevada Cancer Centers 2851 North Tenaya Way
🇺🇸Las Vegas, Nevada, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Cancer Centers of South Texas
🇺🇸San Antonio, Texas, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
University of Michigan Clinical Trials Office
🇺🇸Ann Arbor, Michigan, United States
University of California Davis Cancer Center
🇺🇸Sacramento, California, United States