E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of bone metastases in subjects with advanced breast cancer. |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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). 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. |
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E.2.2 | Secondary objectives of the trial |
- 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.
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal 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. |
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E.4 | Principal 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. - 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. - Thirty days or less since receiving an investigational product or device (ie, does not have marketing authorization) in another clinical trial. - Subject with reproductive potential who will not agree to use effective contraception (as defined by the principal investigator or designee). - Known sensitivity to any of the products to be administered during dosing (eg, zoledronic acid, mammalian derived products, calcium or vitamin D).
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E.5 End points |
E.5.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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End of study is defined as 4 weeks after the anticipated date that the 745th subject experiences their first on-study SRE. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 10 |