Efficacy and Safety of Systemic Treatments of Bone Metastases From Kidney Cancer in Patients Treated With Targeted Therapies
- Registration Number
- NCT03408652
- Lead Sponsor
- Centre Leon Berard
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 1
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A denosumab bone targeted treatment (denosumab or zoledronic acid)
- Primary Outcome Measures
Name Time Method Time to first Skeletal Related Event Up to 54 months after the first inclusion Defined as the time from randomization to first SRE. Patients without event will be censored at the time of the last clinical evaluation.
- Secondary Outcome Measures
Name Time Method Evolution of pain Every 3 months until the 18th month for each patient Proportion of patients that shifted from not taking a strong opioid at baseline
Number of specific event-free survivals Up to 54 months after the first inclusion Specific times from randomization to appearance of the first Skeletal Related Event.
Overall survival Up to 54 months after the first inclusion Measured from the date of randomization to the date of death from any cause
Cost-effectiveness analyses Up to 18 months for each patient All the hospitalization costs will be collected during the timeframe: outpatient, inpatient, and home care
Budget impact analysis Up to 18 months for each patient Quantification of financial consequences of rolling out this kind of medical supportive care strategy throughout the health system.
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 Every 3 months until the 18th month for each patient Incidence of adverse events (AEs) assessed using the National Cancer Institute - Common Terminology Criteria for Adverse Event (NCI-CTCAE) v4 grading scale, specific registration of ONJ or other osteonecrosis and rate of skeletal event per patient during study duration
Evolution of pain severity Every 3 months until the 18th month for each patient Proportion of patients with a clinically meaningful change in pain severity evaluated using a numerical rating scale (NRS)
Patient's condition evaluation Up to 18 months for each patient (evaluated at baseline, months 3, 6, 9 and 18) "EuroQoL 5 Dimensions 5 Levels" questionnaire is a scale used in the health state description. Each items is a three-level scale : having no problems, having some or moderate problems, being unable to do/having extreme problems.The respondents are asked to choose one of the statements which best describes their health status of surveyed day. Rated level can be coded as a number 1, 2, or 3, which indicates having no problems for 1, having some problems for 2, and having extreme problems for 3. As a result, a person's health status can be defined by a 5-digit number, ranging from 11111 (having no problems in all dimensions) to 33333 (having extreme problems in all dimensions).
Cost-utility analysis Up to 18 months for each patient All the hospitalization costs will be collected during the timeframe: outpatient, inpatient, and home care
Evaluation of the different practices for bone metastases treatments Up to 18 months for each patient Financial evaluation of centers' practices (home or hospitalization)
Trial Locations
- Locations (1)
Centre Leon Berard
🇫🇷Lyon, France