Safety and Efficacy of Zoledronic Acid in Patients With Breast Cancer With Metastatic Bone Lesions

NCT00375427 | Completed Phase 3 Results

• 1 other identifier: CZOL446EIT14
• Study Type: interventional
• Target: 430
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this study is to assess the clinical benefit of two different dosing schedules of zoledronic acid in patients with metastatic bone lesions from breast cancer who have already been treated with zoledronic acid for about one year.

Conditions

Breast Cancer With Bone Metastasis

Keywords

Breast cancer; Zoledronic acid; Skeletal related events (SRE)

Outcome Measures

Primary Outcomes (1)

• Annual Overall Skeletal Morbidity Rate (SMR)

  The SMR was computed by summing all Skeletal Related Event(s) (SREs)which occurred during the observation period and dividing it by the ratio "days of observation period / 365.25", for each participant. SRE was defined as: pathologic bone fracture, spinal cord compression, surgery to bone both curative and prophylactic, radiation therapy to bone, or hypercalcemia of malignancy. SMR (years) = 365.25 x SMR(days) where SMR (days) = total number of SREs / total SRE risk period (days). Risk period for SMR was computed as the days from randomization date to the date of last visit.

  12 months

Secondary Outcomes (8)

• Percentage of Participants Experiencing Skeletal Related Event(s) (SREs)

  12 month

• Annual Incidence of Any Skeletal Related Events (SREs)

  12 months

• Median Time to First Skeletal Related Event(s) (SRE)

  12 month

• Percentage of Participants Skeletal Related Event (SRE) Free

  12 months

• Composite Bone Pain Score According to the Brief Pain Inventory (BPI) Questionnaire

  At Baseline, Month 3, Month 6, Month 9 and Month 12

Study Arms (2)

Every 3 months

EXPERIMENTAL

Zoledronic acid as a 15-minute (at least) intravenous (i.v.) infusion every three months. The dose of study drug will be the same administered before the study entry, that is 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Randomized patients will receive a maximum of 4 infusions in this group.

Drug: Zoledronic acid

Every 4 weeks

EXPERIMENTAL

Zoledronic acid as a 15-minute (at least) intravenous (i.v.) infusion every 4 weeks. The dose of study drug will be the same administered before the study entry, that is 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg. Patients randomized to this group will receive up to 12 infusions.

Drug: Zoledronic acid

Interventions

Zoledronic acid DRUG

Zoledronic acid as a 15-minute (at least) intravenous (i.v.) infusion. The dose of study drug will be the same administered before the study entry, that is 4 mg or a reduced dose, i.e. 3.5 mg, or 3.3 mg or 3.0 mg.

Also known as: ZOL446, Zometa®

Every 3 months; Every 4 weeks

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female patients ≥ 18 years of age.
• Written informed consent given.
• Histologically confirmed Stage IV breast cancer with at least one bone metastasis radiologically confirmed.
• Previous treatment with zoledronic acid every 3-4 weeks, for 9-12 infusions over no more than 15 months.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2 .
• Life expectancy ≥ 1 year.

You may not qualify if:

• More than 3 months since last infusion of Zoledronic Acid (Zometa®).
• Treatments with other bisphosphonate than Zoledronic Acid (Zometa®) at any time prior to study entry.
• Serum creatinine \> 3 mg/dL (265 μmol/L) or calculated (Cockcroft-Gault formula) creatinine clearance (CLCr) \< 30 mL/min CrCl = ({\[140-age (years)\] x weight(kg)}/ \[72 x serum creatinine (mg/dL)\])x 0.85
• Corrected (adjusted for serum albumin) serum calcium \< 8 mg/dl (2 mmol/L) or \> 12 mg/dL ( 3.0 mmol/L).
• Current active dental problem including infection of the teeth or jawbone (maxilla or mandibular); dental or fixture trauma, or a recurrent or prior diagnosis of osteonecrosis of the jaw (ONJ), of exposed bone in the mouth, or of slow healing after dental procedures.
• Recent (within 6 weeks) or planned dental or jaw surgery (e.g. extraction, implants).
• Pregnant patients (with a positive pregnancy test prior to study entry) or lactating patients. Women of childbearing potential not using effective methods of birth control (e.g. abstinence, oral contraceptives or implants, IUD, vaginal diaphragm or sponge, or condom with spermicide).
• History of non-compliance to medical regimens or potential unreliable behavior.
• Known sensitivity to study drug(s) or class of study drug(s).
• Patients with severe medical condition(s) that in the view of the investigator prohibits participation in the study
• Use of any other investigational agent in the last 30 days.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (1)

Novartis Investigative Site

Forlì, Italy

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Zoledronic Acid

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2006
• First Posted: September 13, 2006
• Study Start: February 1, 2006
• Primary Completion: February 1, 2010
• Last Updated: April 11, 2012
• Results First Posted: August 4, 2011

Record last verified: 2011-07

Locations

IT (1)