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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10055113 |
E.1.2 | Term | Breast cancer metastatic |
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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 compare the treatment effect of denosumab with zoledronic acid on the first occurrence of a skeletal related event SRE in subjects with advanced breast cancer and bone metastases |
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E.2.2 | Secondary objectives of the trial |
To compare the treatment effect of denosumab with zoledronic acid on the first occurrence of SRE or hypercalcemia of malignancy HCM To compare the treatment effect of denosumab with zoledronic acid on the first use of radiation to bone To compare the treatment effect of denosumab with zoledronic acid on first-and-subsequent on study SRE multiple event analysis To compare the treatment effect of denosumab with zoledronic acid on pain and analgesic use 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 |
61623; adult man or woman with histologically or cytologically confirmed breast adenocarcinoma 61623; current or prior radiographic x-ray, magnetic resonance imaging MRI or computer tomography CT evidence of at least 1 bone metastasis 61623; life expectancy 6 months 61623; Eastern Cooperative Oncology Group ECOG performance status of 0, 1, or 2 61623; adequate organ function as defined by the following criteria - serum aspartate aminotransferase AST 61603; 5 x upper limit of normal ULN - serum alanine aminotransferase ALT 61603; 5 x ULN - serum total bilirubin 61603; 2 x ULN - creatinine clearance Cockroft-Gault 61619; 30 mL/min - albumin-adjusted serum calcium 61619; 2.0 mmol/L 8.0 mg/dL and 61603; 2.9 mmol/L 11.5 mg/dL 61623; before any study-specific procedure, the appropriate written informed consent must be obtained |
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E.4 | Principal exclusion criteria |
61623; current or prior IV bisphosphonate administration 61623; current or prior oral bisphosphonate treatment for bone metastasis 61623; prior administration of OPG construct ie, AMGN-0007, Fc-OPG or denosumab 61623; known brain metastases 61623; known impending fracture, defined as evidence of osteolytic lesions with cortical bone destruction exceeding 50 in the femur 61623; prior history or current evidence of osteonecrosis/osteomyelitis of the jaw 61623; active dental or jaw condition that requires oral surgery 61623; non-healed dental/oral surgery 61623; planned invasive dental procedure for the course of the study 61623; evidence of any of the following conditions per subject self report or medical chart review - subjects with prior malignancies except breast cancer, basal cell carcinoma or in situ cervical cancer may be enrolled if disease free for 61619; 3 years - unstable systemic disease including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, or myocardial infarction within 6 months before randomization - major surgery including surgery to bone , or significant traumatic injury occurring within 4 weeks before randomization - known infection with human immunodeficiency virus - active infection with Hepatitis B virus or Hepatitis C virus 61623; 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 61623; thirty days or less since receiving an unapproved ie, no marketing authorization has been granted in that country product or device in another clinical trial 61623; subjects must be surgically sterile, postmenopausal, or must agree to use effective contraception during the period of therapy. Female subjects with reproductive potential must have a negative pregnancy test serum or urine within 7 days before randomization. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate 61623; known sensitivity to any of the products to be administered during the study 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 ie, pathologic, radiation therapy to bone, 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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Information not present in EudraCT |
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 | Information not present in EudraCT |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 5 |