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

Sponsor

Centre Leon Berard (Other)

Overall Status

Terminated

CT.gov ID

NCT03408652

Collaborator

(none)

Enrollment

Location

Arms

15.3

Actual Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Renal Cell Carcinoma	Drug: denosumab	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

1 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Supportive Care

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

Actual Study Start Date :

Mar 15, 2019

Actual Primary Completion Date :

Jun 22, 2020

Actual Study Completion Date :

Jun 22, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A bone targeted treatment (denosumab or zoledronic acid)	Drug: denosumab 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. Other Names: zoledronic acid
No Intervention: Arm B no specific treatment

Arm

Intervention/Treatment

Experimental: Arm A

bone targeted treatment (denosumab or zoledronic acid)

Drug: denosumab

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.

Other Names:

zoledronic acid

No Intervention: Arm B

no specific treatment

Outcome Measures

Primary Outcome Measures

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

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.
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.
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).
Overall survival [Up to 54 months after the first inclusion]
Measured from the date of randomization to the date of death from any cause
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.