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: July 8, 2014
Last verified: July 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 composite score was calculated as the average of items 3, 4, 5 and 6 (worst pain, least pain, average pain and pain right now). A positive change from baseline indicates improvement.

  • 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 improvement.

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

  Show 92 Study Locations
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: July 8, 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
Bone Neoplasms
Bone Marrow Diseases
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplastic Processes
Pathologic Processes
Bone Diseases
Musculoskeletal Diseases
Hematologic Diseases
Zoledronic acid
Diphosphonates
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 18, 2014