Efficacy and Safety of Systemic Treatments of Bone Metastases From Kidney Cancer in Patients Treated With Targeted Therapies

Multicenter Randomized Phase III Study Evaluating the Efficacy and Safety of Systemic Treatments of Bone Metastases From Kidney Cancer in Patients Treated With Targeted Therapies

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.