Back to resultsEfficacy and Safety of Systemic Treatments of Bone Metastases From Kidney Cancer in Patients Treated With Targeted Therapies (MOSCAR)
Primary Purpose
Metastatic Renal Cell Carcinoma
Status
Terminated
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
denosumab
Sponsored by
About this trial
This is an interventional supportive care trial for Metastatic Renal Cell Carcinoma focused on measuring Bone Metastases
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.
Sites / Locations
- Centre Leon Berard
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Arm A
Arm B
Arm Description
bone targeted treatment (denosumab or zoledronic acid)
no specific treatment
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Number of specific event-free survivals
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
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
Proportion of patients with a clinically meaningful change in pain severity evaluated using a numerical rating scale (NRS)
Evolution of pain
Proportion of patients that shifted from not taking a strong opioid at baseline
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.
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).
Overall survival
Measured from the date of randomization to the date of death from any cause
Evaluation of the different practices for bone metastases treatments
Financial evaluation of centers' practices (home or hospitalization)
Cost-utility analysis
All the hospitalization costs will be collected during the timeframe: outpatient, inpatient, and home care
Cost-effectiveness analyses
All the hospitalization costs will be collected during the timeframe: outpatient, inpatient, and home care
Budget impact analysis
Quantification of financial consequences of rolling out this kind of medical supportive care strategy throughout the health system.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03408652
Brief Title
Efficacy and Safety of Systemic Treatments of Bone Metastases From Kidney Cancer in Patients Treated With Targeted Therapies
Acronym
MOSCAR
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
2. Study Status
Record Verification Date
October 2021
Overall Recruitment Status
Terminated
Why Stopped
lack of recruitment
Study Start Date
March 15, 2019 (Actual)
Primary Completion Date
June 22, 2020 (Actual)
Study Completion Date
June 22, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Leon Berard
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Renal Cell Carcinoma
Keywords
Bone Metastases
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A
Arm Type
Experimental
Arm Description
bone targeted treatment (denosumab or zoledronic acid)
Arm Title
Arm B
Arm Type
No Intervention
Arm Description
no specific treatment
Intervention Type
Drug
Intervention Name(s)
denosumab
Other Intervention Name(s)
zoledronic acid
Intervention Description
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.
Primary Outcome Measure Information:
Title
Time to first Skeletal Related Event
Description
Defined as the time from randomization to first SRE. Patients without event will be censored at the time of the last clinical evaluation.
Time Frame
Up to 54 months after the first inclusion
Secondary Outcome Measure Information:
Title
Number of specific event-free survivals
Description
Specific times from randomization to appearance of the first Skeletal Related Event.
Time Frame
Up to 54 months after the first inclusion
Title
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Description
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
Time Frame
Every 3 months until the 18th month for each patient
Title
Evolution of pain severity
Description
Proportion of patients with a clinically meaningful change in pain severity evaluated using a numerical rating scale (NRS)
Time Frame
Every 3 months until the 18th month for each patient
Title
Evolution of pain
Description
Proportion of patients that shifted from not taking a strong opioid at baseline
Time Frame
Every 3 months until the 18th month for each patient
Title
Patient's condition evaluation
Description
"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.
Time Frame
Up to 9 months for each patient (evaluated at baseline, months 3, 6, 9)
Title
Patient's condition evaluation
Description
"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).
Time Frame
Up to 18 months for each patient (evaluated at baseline, months 3, 6, 9 and 18)
Title
Overall survival
Description
Measured from the date of randomization to the date of death from any cause
Time Frame
Up to 54 months after the first inclusion
Title
Evaluation of the different practices for bone metastases treatments
Description
Financial evaluation of centers' practices (home or hospitalization)
Time Frame
Up to 18 months for each patient
Title
Cost-utility analysis
Description
All the hospitalization costs will be collected during the timeframe: outpatient, inpatient, and home care
Time Frame
Up to 18 months for each patient
Title
Cost-effectiveness analyses
Description
All the hospitalization costs will be collected during the timeframe: outpatient, inpatient, and home care
Time Frame
Up to 18 months for each patient
Title
Budget impact analysis
Description
Quantification of financial consequences of rolling out this kind of medical supportive care strategy throughout the health system.
Time Frame
Up to 18 months for each patient
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sylvie NEGRIER, PhD
Organizational Affiliation
Centre Leon Berard
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre Leon Berard
City
Lyon
ZIP/Postal Code
69008
Country
France
12. IPD Sharing Statement
Learn more about this trial
Efficacy and Safety of Systemic Treatments of Bone Metastases From Kidney Cancer in Patients Treated With Targeted Therapies
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