lack of recruitment

Multicenter, randomized, open-label, 2-arm, parallel-group, phase III study whose goal is to assess the efficacy and safety profile of bone-targeted treatments (Arm A: denosumab or zoledronic acid) versus the control arm (Arm B: no specific treatment) in patients with bone metastases under targeted therapy for Metastatic Renal Cell Carcinoma.

Inclusion Criteria:

• Age ≥ 18 years.
• Histologically proven mRCC.
• Administration of one of the systemic agents in use for the treatment of mRCC (no more than three prior systemic therapy regimens). Patients with at least 6 months of 1st line treatment and a bone event may be included.
• More than 1 bone metastasis.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 2.
• Adequate renal function (serum creatinine ≤ 200 mmol/L or creatinine clearance ≥ 30 mL/min according to Cockroft formula or MDRD formula for patients older than 65 years).
• Covered by a medical insurance.
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
• Signed informed consent.
• Accepting to use effective contraception during study treatment and within 5 months after final dose of study therapy.

Exclusion Criteria:

• Prior bisphosphonate or denosumab treatment in the year before inclusion.
• Imminent or ongoing nerve or spinal compression as per the investigator's judgement.
• Ongoing first-line therapy, started for less than 6 months (patients with BM at time of metastases diagnosis will initially benefit from the angiogenesis targeted agents used and are not at higher risk).
• Anticancer treatment under investigation.
• Paraneoplastic hypercalcemia (corrected total calcium > 2.7 mmol/L).
• Grade 4 toxicity under previous targeted agents.
• Liver failure (AST and/or ALT ≥ 5.0 x upper limit of normal (ULN) or total bilirubin beyond normal limits).
• Severe hypocalcaemia > 2.8 mmol/l.
• Fructose intolerance.
• Invasive dental procedure (i.e. tooth extraction, dental implants, oral surgery) within the 10 days prior to randomization or required dental procedures at the pre-inclusion dental examination.
• Psychological, familial, sociological, geographical conditions that would limit compliance with study protocol requirements.
• Pregnant or breastfeeding woman. Females of child-bearing potential must have a negative serum pregnancy test within 7 days prior inclusion.
• Life expectancy ≤ 3 months.
• Participation to another clinical trial that might interfere with the evaluation of the main criterion.
• Known hypersensitivity to the active substance or to any of the excipients of bisphosphonate or denosumab.