Clinical trial NCT03408652: Efficacy and Safety of Systemic Treatments of Bone Metastases From Kidney Cancer in Patients Treated With Targeted Therapies
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Metastatic Renal Cell Carcinoma
Keywords: Bone Metastases
Lead sponsor: Centre Leon Berard
Sponsor class: OTHER
First posted: 2018-01-24
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Time to first Skeletal Related Event
timeFrame: Up to 54 months after the first inclusion
Secondary outcomes:
measure: Number of specific event-free survivals
timeFrame: Up to 54 months after the first inclusion
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: Every 3 months until the 18th month for each patient
measure: Evolution of pain severity
timeFrame: Every 3 months until the 18th month for each patient
measure: Evolution of pain
timeFrame: Every 3 months until the 18th month for each patient
measure: Patient's condition evaluation
timeFrame: Up to 9 months for each patient (evaluated at baseline, months 3, 6, 9)
measure: Patient's condition evaluation
timeFrame: Up to 18 months for each patient (evaluated at baseline, months 3, 6, 9 and 18)
measure: Overall survival
timeFrame: Up to 54 months after the first inclusion
measure: Evaluation of the different practices for bone metastases treatments
timeFrame: Up to 18 months for each patient
measure: Cost-utility analysis
timeFrame: Up to 18 months for each patient
measure: Cost-effectiveness analyses
timeFrame: Up to 18 months for each patient
measure: Budget impact analysis
timeFrame: Up to 18 months for each patient
Other outcomes:
Locations:
city: Lyon
country: France
facility: Centre Leon Berard
Study officials:
affiliation: Centre Leon Berard
name: Sylvie NEGRIER, PhD
role: PRINCIPAL_INVESTIGATOR
References: