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

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.

Study Overview

• Status: Terminated
• Conditions: Metastatic Renal Cell Carcinoma
• Intervention / Treatment: Drug: denosumab

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Lyon, France, 69008
    • Centre Leon Berard

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first Skeletal Related Event	Defined as the time from randomization to first SRE. Patients without event will be censored at the time of the last clinical evaluation.	Up to 54 months after the first inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of specific event-free survivals	Specific times from randomization to appearance of the first Skeletal Related Event.	Up to 54 months after the first inclusion
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	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	Every 3 months until the 18th month for each patient
Evolution of pain severity	Proportion of patients with a clinically meaningful change in pain severity evaluated using a numerical rating scale (NRS)	Every 3 months until the 18th month for each patient
Evolution of pain	Proportion of patients that shifted from not taking a strong opioid at baseline	Every 3 months until the 18th month for each patient
Patient's condition evaluation	"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.	Up to 9 months for each patient (evaluated at baseline, months 3, 6, 9)
Patient's condition evaluation	"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).	Up to 18 months for each patient (evaluated at baseline, months 3, 6, 9 and 18)
Overall survival	Measured from the date of randomization to the date of death from any cause	Up to 54 months after the first inclusion
Evaluation of the different practices for bone metastases treatments	Financial evaluation of centers' practices (home or hospitalization)	Up to 18 months for each patient
Cost-utility analysis	All the hospitalization costs will be collected during the timeframe: outpatient, inpatient, and home care	Up to 18 months for each patient
Cost-effectiveness analyses	All the hospitalization costs will be collected during the timeframe: outpatient, inpatient, and home care	Up to 18 months for each patient
Budget impact analysis	Quantification of financial consequences of rolling out this kind of medical supportive care strategy throughout the health system.	Up to 18 months for each patient

Collaborators and Investigators

• Sponsor: Centre Leon Berard
• Investigators: Principal Investigator: Sylvie NEGRIER, PhD, Centre Leon Berard

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2019
• Primary Completion (Actual): June 22, 2020
• Study Completion (Actual): June 22, 2020

Study Registration Dates

• First Submitted: January 8, 2018
• First Submitted That Met QC Criteria: January 23, 2018
• First Posted (Actual): January 24, 2018

Study Record Updates

• Last Update Posted (Actual): October 22, 2021
• Last Update Submitted That Met QC Criteria: October 14, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Bone Metastases
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplastic Processes; Kidney Neoplasms; Carcinoma, Renal Cell; Neoplasm Metastasis; Physiological Effects of Drugs; Bone Density Conservation Agents; Zoledronic Acid; Denosumab
• Other Study ID Numbers: MOSCAR; 2017-004075-31 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No