Treatment of bone metastases in subjects with advanced breast cancer. MedDRA version: 8.1 Level: LLT Classification code 10027452 Term: Metastases to bone
Conditions
Interventions
Product Name: Denosumab
Product Code: AMG 162
Pharmaceutical Form: Solution for injection
CAS Number: 615258-40-7
Current Sponsor code: AMG 162
Other descriptive name: Abx 1-6 CHO OPG Ligand mAb IgG2
Human Monoclonal Antibody to RANKL
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 70-
Pharmaceutical form of the placebo: Solution for injection
Rout
Sponsors
Amgen Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Adult (men included) with histologically or cytologically confirmed breast adenocarcinoma. - Current or prior radiographic (ie, x-ray, computer tomography [CT], or magnetic resonance imaging [MRI]) evidence of at least 1 bone metastasis. - Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2. - Adequate organ function as defined by the following criteria: 1. Serum aspartate aminotransferase (AST) less than or equal to 5 x upper limit of normal (ULN). 2. Serum alanine aminotransferase (ALT) less than or equal to 5 x ULN. 3. Serum total bilirubin less than or equal to 2 x ULN. 4. Creatinine clearance greater than or equal to 30 mL/min. 5. Albumin-adjusted serum calcium greater than or equal to 2.0 mmol/L (8.0 mg/dL) and less than or equal to 2.9 mmol/L (11.5 mg/dL). Albumin-adjusted serum calcium, if applicable, will be calculated by the central laboratory. - Before any study-specific procedure, the appropriate written informed consent must be obtained. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Current or prior IV bisphosphonate administration. - Current or prior oral bisphosphonate treatment for bone metastasis. - Planned radiation therapy or surgery to bone. - Prior administration of denosumab. - Known brain metastases. - Life expectancy less than 6 months. - Prior history or current evidence of osteonecrosis/osteomyelitis of the jaw. - Active dental or jaw condition which requires oral surgery. - Non-healed dental/oral surgery. - Planned invasive dental procedure for the course of the study. - Evidence of any of the following conditions per subject self report or medical chart review: 1. Any prior malignancy (other than breast cancer, basal cell carcinoma, or in situ cervical cancer) with active disease within 3 years before randomization. 2. Known infection with human immunodeficiency virus. 3. Active infection with Hepatitis B or Hepatitis C virus. 4. Any organic or psychiatric disorder that, in the opinion of the investigator, might prevent the subject from completing the study or interfere with the interpretation of the study results. 5. Thirty days or less since receiving an investigational product or device (ie, does not have marketing authorization) in another clinical trial. 6. Subject with reproductive potential who will not agree to use effective contraception (as defined by the principal investigator or designee). 7. Known sensitivity to any of the products to be administered during dosing (eg, zoledronic acid, mammalian derived products, calcium or vitamin D).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine if denosumab is non-inferior to zoledronic acid (Zometa) with respect to the first on-study occurrence of a skeletal related event (SRE) in subjects with advanced breast cancer and bone metastases. SRE is defined as pathologic fracture (vertebral or non-vertebral), radiation therapy to bone (including the use of radioisotopes), surgery to bone, or spinal cord compression in subjects with advanced breast cancer and bone metastases.;Secondary Objective: - To determine if denosumab is superior to zoledronic acid with respect to the first on study SRE. - To determine if denosumab is superior to zoledronic acid with respect to the first-and-subsequent on-study SRE (multiple event analysis). - To assess the safety and tolerability of denosumab compared with zoledronic acid. ;Primary end point(s): Time to the first on-study SRE (non-inferiority) SRE is an aggregate endpoint that includes pathologic fracture (vertebral or non vertebral), radiation therapy to bone (including the use of radioisotopes), surgery to bone, or spinal cord compression. | — |
Countries
Austria, Czech Republic, Denmark, Estonia, Germany, Hungary, Italy, Latvia, Lithuania, Netherlands, Spain, Sweden, United Kingdom
Outcome results
None listed