Metastatic Renal Cell Carcinoma
Conditions
Keywords
Bone Metastases
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.
Interventions
DRUGdenosumab
Single subcutaneous injection of denosumab 120 mg every 4 weeks One intravenous infusion of zoledronic acid 4 mg every 4 weeks, according to labelled use.
Sponsors
Centre Leon Berard
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| 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 |
| Patient's condition evaluation | Up to 9 months for each patient (evaluated at baseline, months 3, 6, 9) | Functional Assessment of cancer Therapy-General (FACT-G) questionnaire, made of 27 items measuring the respondents' health state, each of which is answered using a five-point scale from 0 (not at all) to 4 (very much). Questions are phrased so that higher numbers indicate a better health state. Subscale scores are added to obtain total score. |
| 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. |
| Evaluation of the different practices for bone metastases treatments | Up to 18 months for each patient | Financial evaluation of centers' practices (home or hospitalization) |
| 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 |
| 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. |
| Overall survival | Up to 54 months after the first inclusion | Measured from the date of randomization to the date of death from any cause |
Countries
France
Outcome results
None listed