Prevention of Symptomatic Skeletal Events With Denosumab Administered Every 4 Weeks Versus Every 12 Weeks

Exclusion Criteria

• •Definite contraindication for denosumab (e.g. hypocalcaemia \[Albumin-corrected serum calcium \< 2.0 mmol/l\]).
• •History or current evidence of osteonecrosis of the jaw.
• •Non-healed mucosa in oral cavity (by surgery or as a side effect of any other treatment).
• •Jaw or dental conditions that require oral surgery or if surgery or invasive dental procedures are planned.
• •Prior use of denosumab for bone metastases (dose 120 mg every 4 weeks) or bisphosphonates to treat bone metastases. Patients treated with denosumab or bisphosphonates against osteopenia or osteoporosis are allowed to enter the trial if the last dose was more than 28 days before randomization.
• •Patients with known osteoporosis (T-score ≤ -2.5) at study entry (since fractures from osteoporosis are difficult to be discriminated from fractures through bone metastases).
• •Radiotherapy or surgery to the bone within the last two weeks before randomization or planned within 6 weeks after randomization.
• •Presence or history of CNS metastases or leptomeningeal disease. A MRI evaluation within 12 weeks before randomization must be performed in case of suspicious symptoms.
• •Psychiatric disorder precluding understanding of information on trial related topics, giving informed consent, filling out QoL forms.
• •Concurrent treatment in a clinical trial with SSE or SRE as primary endpoint.
• •Known hypersensitivity to trial drug or hypersensitivity to any other component of the trial drug (e.g. fructose).
• •Any concomitant drugs contraindicated for use with the trial drugs according to the approved product information.
• •Any psychological, familial, sociological or geographical condition potentially hampering compliance with the trial protocol.