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

• ClinicalTrials.gov Identifier: NCT00320710
• Recruitment Status: Completed
• First Posted: May 3, 2006
• Results First Posted: August 4, 2014
• Last Update Posted: August 22, 2014
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Tracking Information

• First Submitted Date: April 28, 2006
• First Posted Date: May 3, 2006
• Results First Submitted Date: July 8, 2014
• Results First Posted Date: August 4, 2014
• Last Update Posted Date: August 22, 2014
• Study Start Date: February 2006
• Actual Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 8, 2014)

Proportion of Patients Who Experienced at Least One Skeletal Related Event (SRE) [ Time Frame: 52 weeks ]

An SRE was defined as a pathologic fracture (vertebral and non-vertebral), spinal cord compression, radiation to bone or surgery to bone.

• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: August 18, 2014)

• Time to First SRE [ Time Frame: 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.
• Time to First Individual Type of SRE [ Time Frame: 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 Mean Composite Brief Pain Inventory (BPI) Score [ Time Frame: 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.
• Change From Baseline in Mean Analgesic Score [ Time Frame: 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.
• Change From Baseline in Urinary N-telopeptide / Creatinine Ratio [ Time Frame: baseline, 48 weeks ]
  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 ]
  Serum samples were collected to obtain bone specific alkaline phosphatase values.
• Skeletal Morbidity Rate [ Time Frame: 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).

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Breast Cancer

Intervention

• Drug: Zoledronic acid
  4mg IV
  Other Names:

  • Zoledronate
  • ZOL446
  • Zometa
• Drug: Placebo
  Placebo to zoledronic acid

Study Arms

• Experimental: Zoledronic acid every (q) 4 weeks
  Participants received 4mg of zoledronic acid intravenously (IV) infusion q 4 weeks.
  Intervention: Drug: Zoledronic acid
• 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.
  Interventions:

  • Drug: Zoledronic acid
  • Drug: Placebo
• 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.
  Interventions:

  • Drug: Zoledronic acid
  • Drug: Placebo

• Publications *: Hortobagyi GN, Van Poznak C, Harker WG, Gradishar WJ, Chew H, Dakhil SR, Haley BB, Sauter N, Mohanlal R, Zheng M, Lipton A. Continued Treatment Effect of Zoledronic Acid Dosing Every 12 vs 4 Weeks in Women With Breast Cancer Metastatic to Bone: The OPTIMIZE-2 Randomized Clinical Trial. JAMA Oncol. 2017 Jul 1;3(7):906-912. doi: 10.1001/jamaoncol.2016.6316.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 8, 2014): 416
• Original Enrollment: Not Provided
• Actual Study Completion Date: July 2013
• Actual Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States
• Removed Location Countries: Puerto Rico

Administrative Information

• NCT Number: NCT00320710
• Other Study ID Numbers: CZOL446E2352
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Novartis ( Novartis Pharmaceuticals )
• Original Responsible Party: Not Provided
• Current Study Sponsor: Novartis Pharmaceuticals
• Original Study Sponsor: Novartis
• Collaborators: Not Provided

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

• PRS Account: Novartis
• Verification Date: August 2014