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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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00320710
First received: April 28, 2006
Last updated: August 18, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: Zoledronic acid
Drug: Placebo
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Proportion of Patients Who Experienced at Least One Skeletal Related Event (SRE) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    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:
  • Time to First SRE [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    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.

  • Time to First Individual Type of SRE [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    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 Mean Composite Brief Pain Inventory (BPI) Score [ Time Frame: baseline, 52 weeks ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Mean Analgesic Score [ Time Frame: baseline, 52 weeks ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Urinary N-telopeptide / Creatinine Ratio [ Time Frame: baseline, 48 weeks ] [ Designated as safety issue: No ]
    Urine samples were collected to obtain n-telopeptide and creatinine values.

  • Change From Baseline in Serum Bone Specific Alkaline Phosphatase [ Time Frame: baseline, 48 weeks ] [ Designated as safety issue: No ]
    Serum samples were collected to obtain bone specific alkaline phosphatase values.

  • Skeletal Morbidity Rate [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    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).


Enrollment: 416
Study Start Date: February 2006
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Zoledronic acid every (q) 4 weeks
Participants received 4mg of zoledronic acid intravenously (IV) infusion q 4 weeks.
Drug: Zoledronic acid
4mg IV
Other Names:
  • Zoledronate
  • ZOL446
  • Zometa
Experimental: Zoledronic acid q 12 weeks
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.
Drug: Zoledronic acid
4mg IV
Other Names:
  • Zoledronate
  • ZOL446
  • Zometa
Drug: Placebo
Placebo to zoledronic acid
Experimental: Placebo / 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.
Drug: Zoledronic acid
4mg IV
Other Names:
  • Zoledronate
  • ZOL446
  • Zometa
Drug: Placebo
Placebo to zoledronic acid

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00320710

  Hide Study Locations
Locations
United States, Alaska
Providence Alaska Medical Center Cancer Research
Anchorage, Alaska, United States, 99508
United States, Arkansas
Heritage Physicians Group Oncology
Hot Springs, Arkansas, United States, 71913
The Center for Chest Care
Springdale, Arkansas, United States, 72764
United States, California
Pacific Cancer Medical Center, Inc.
Anaheim, California, United States, 92801
South Bay Oncology Hematology Partners
Campbell, California, United States, 95008
Bay Area Cancer Research
Concord, California, United States, 94520
Pacific Coast Hem/Onc
Fountain Valley, California, United States, 92708
Wilshire Oncology Medical Group
La Verne, California, United States, 91750
Kenmar Research Institute
Los Angeles, California, United States, 90057
North Valley Hematology/Oncology Providence Holy Cross Medical
Northridge, California, United States, 91328
Medical Oncology Care Associates
Orange, California, United States, 92868
Ventura County Hematology and Oncology
Oxnard, California, United States, 93030
The Office of Dr. Swarna Chanduri, MD
Pomona, California, United States, 91767
Access Clinical Research
Rancho Mirage, California, United States, 92270
Cancer and Blood of the Desert
Rancho Mirage, California, United States, 92270
University of California Davis Cancer Center
Sacramento, California, United States, 95817
University of California at Los Angeles
Sylmar, California, United States, 91342
United States, Colorado
Denver Health Medical Center CACZ885M2301
Denver, Colorado, United States, 80204-4507
United States, Connecticut
Eastern Connecticut Hematology & Oncology Associates
Norwich, Connecticut, United States, 06360
United States, District of Columbia
Georgetown University/Lombardi Cancer Center
Washington, District of Columbia, United States, 20007-2197
Washington Hospital Center
Washington, District of Columbia, United States, 20010
United States, Florida
Baptist Cancer Center
Jacksonville, Florida, United States, 32209
Pasco Hernando Oncology
New Port Richey, Florida, United States, 34652
The Office of Dr. Elizabeth Tan-Chiu, MD PA
Planatation, Florida, United States, 33324
United States, Georgia
Suburban Hematology-Oncology
Lawrenceville, Georgia, United States, 30045
United States, Illinois
NorthwesternUniv.Med.School/Robert H. Lurie Comp.Cancer Ctr
Chicago, Illinois, United States, 60611
Evanston Northwestern Healthcare Medical Group
Evanston, Illinois, United States, 60201
Edward Cancer Center
Naperville, Illinois, United States, 60540
Midwest Cancer Research Group
Skokie, Illinois, United States, 60077
United States, Indiana
Investigative Clinical Research
Indianapolis, Indiana, United States, 46254
Cancer Care Center
New Albany, Indiana, United States, 47150
Associated Physicians & Surgeons Clinic
Terre Haute, Indiana, United States, 47804
United States, Iowa
Medical Associates Clinic, PC
Dubuque, Iowa, United States, 52001
University of Iowa Health Care
Iowa City, Iowa, United States, 52242-1091
Siouxland Hematology-Oncology Associates LLP
Sioux City, Iowa, United States, 51101
United States, Kansas
Cotton O'Neil Oncology Clinic
Topeka, Kansas, United States, 66606
Cancer Center of Kansas
Witchita, Kansas, United States, 67214-3728
United States, Kentucky
Kentucky Lung Clinic & Kentucky Sleep Clinic
Hazard, Kentucky, United States, 41701
Lexington Oncology Associates
Lexington, Kentucky, United States, 40503
United States, Louisiana
Cabrini Center for Cancer Care
Alexandria, Louisiana, United States, 71301
Southwest Oncology Associates Ltd.
Lafayette, Louisiana, United States, 70503
United States, Maryland
St. Agnes Hospital
Baltimore, Maryland, United States, 21229
Greenbaum Cancer Center
Baltimore, Maryland, United States, 21201-1595
The Harry and Jeanette Weinberg Cancer Institute at Franklin
Baltimore, Maryland, United States, 21237
Center for Cancer & Blood Disorders
Bethesda, Maryland, United States, 20817
Frederick Memorial Hospital
Frederick, Maryland, United States, 21701
United States, Massachusetts
Caritas Holy Family Hospital
Methuen, Massachusetts, United States, 01844
United States, Michigan
University of Michigan Clinical Trials Office
Ann Arbor, Michigan, United States, 48109
Henry Ford Hospital Oncology
Detroit, Michigan, United States, 48202
Wayne State University
Detroit, Michigan, United States, 48201
Oncology Care Associates, PLLC
St. Joseph, Michigan, United States, 49085
United States, Minnesota
St. Luke's Hospital and Health Network
Duluth, Minnesota, United States, 55805
Fairview Clinical Trial Services
Minneapolis, Minnesota, United States, 55414
Univ. of Minnesota Cancer Center 420 Delaware St.
Minneapolis, Minnesota, United States, 55455
Hubert H. Humphrey Cancer Center
Robbinsdale, Minnesota, United States, 55422
United States, Mississippi
Jackson Oncology Associates
Jackson, Mississippi, United States, 39202
United States, Missouri
Capitol Comprehensive Cancer Care Clinic
Jefferson City, Missouri, United States, 65109
The Center for Cancer Care and Research
St. Louis, Missouri, United States, 63141
United States, Nebraska
Nebraska Hematology-Oncology PC
Lincoln, Nebraska, United States, 68506
United States, Nevada
Nevada Cancer Centers 2851 North Tenaya Way
Las Vegas, Nevada, United States, 89109
United States, New Jersey
Center for Cancer and Hematologic Disease
Cherry Hill, New Jersey, United States, 08003
Saint Barnabas Medical Center
Livingston, New Jersey, United States, 07039
Somerset Hematology Oncology Associates
Somerset, New Jersey, United States, 08873
United States, New York
Advanced Oncology Associates
Armonk, New York, United States, 10504
Arena Oncology Associates, PC
Great Neck, New York, United States, 11021
Benedictine Hospital
Kingston, New York, United States, 12401
Beth Israel Medical Center
New York, New York, United States, 10003
Columbia Presbyterian Medical Center
New York, New York, United States, 10032
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Jmaes P. Wilmot Cancer Center
Rochester, New York, United States, 14642
United States, North Carolina
Alamance Regional Medical Cancer Center
Burlington, North Carolina, United States, 27215
Northeast Oncology Associates Suite 250
Concord, North Carolina, United States, 28025
United States, Ohio
Barberton Citizens Hospital
Barberton, Ohio, United States, 44203
Gabrail Cancer Center
Canton, Ohio, United States, 44718
Ohio Cancer Specialists
Mansfield, Ohio, United States, 44907
Hematology/Oncology Consultants Inc.
West Worthington, Ohio, United States, 43235
Trilogy Cancer Care
Wooster, Ohio, United States, 44691
United States, Oregon
Bay Area Hospital - Pharmacy
Coos Bay, Oregon, United States, 97420
The Corvallis Clinic, P.C.
Corvallis, Oregon, United States, 97330
United States, Pennsylvania
Milton S Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
Lancaster Cancer Center
Lancaster, Pennsylvania, United States, 17601
U of Pittsburgh Cancer Institute Magee-Womens Hospital
Pittsburgh, Pennsylvania, United States, 15213
Guthrie Cancer Center
Sayre, Pennsylvania, United States, 18840
Mainline Oncology Hematology Assoc.
Wynnewood, Pennsylvania, United States, 19096
United States, South Carolina
M. Francisco Gonzalez, MD., FACP
Columbia, South Carolina, United States, 29203
Santee Hematology/Oncology
Sumter, South Carolina, United States, 29150
United States, Texas
MD Anderson Cancer Center/University of Texas 1155 Herman Pressler Street
Houston, Texas, United States, 77031
Cancer Centers of South Texas
San Antonio, Texas, United States, 78229
United States, Washington
Providence Everett Medical Clinic
Everett, Washington, United States, 98201
Seattle Cancer Care Alliance Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
Rockwood Clinic Rockwood Clinic, PS
Spokane, Washington, United States, 99202
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Additional Information:
No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00320710     History of Changes
Other Study ID Numbers: CZOL446E2352
Study First Received: April 28, 2006
Results First Received: July 8, 2014
Last Updated: August 18, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
Breast cancer
zoledronic acid
bone metastases

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasm Metastasis
Breast Diseases
Neoplasms
Neoplasms by Site
Neoplastic Processes
Pathologic Processes
Skin Diseases
Diphosphonates
Zoledronic acid
Bone Density Conservation Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 20, 2014