Study of Denosumab vs. Zoledronic Acid to Treat Bone Metastases in Subjects With Advanced Cancer or Multiple Myeloma.

Study Overview
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Brief Summary
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The purpose of this study is to determine if denosumab is non-inferior to zoledronic acid (Zometa®) in the treatment of bone metastases (lytic bone lesions from multiple myeloma) in subjects with advanced cancer and multiple myeloma (excluding breast and prostate cancer)

Official Title
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A Randomized, Double-Blind, Multicenter Study of Denosumab Compared With Zoledronic Acid (Zometa) in the Treatment of Bone Metastases in Subjects With Advanced Cancer (Excluding Breast and Prostate Cancer) or Multiple Myeloma.

Conditions
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Bone Metastases

Intervention / Treatment
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* Biological: Denosumab
* Drug: Zoledronic Acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults with histologically/cystologically confirmed advanced cancers including solid tumors, multiple myeloma, and lymphoma Radiographic evidence of at least one bone metastasis (or lytic bone lesion from multiple myeloma); ECOG performance status 0, 1, or 2 Adequate organ function Exclusion Criteria: Diagnosis of breast or prostate cancer Current or prior intravenous bisphosphonate administration Current or prior oral bisphosphonates for bone metastases, life expectancy of less than 6 months Prior history or current evidence of osteonecrosis/osteomyelitis of the jaw

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: zoledronic acid<br>denosumab placebo with active zoledronic acid | Drug: Zoledronic Acid<br>* 4 milligrams intravenous Zoledronic Acid over minimum 15 minutes every 4 weeks<br>* Other names: Zometa;|
| Experimental: denosumab<br>active denosumab with zoledronic acid placebo | Biological: Denosumab<br>* 120 milligrams by subcutaneous injection every 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to the First On-Study Skeletal-Related Event (Non-Inferiority) | Time to the first on-study skeletal-related event (SRE) using a non-inferiority analysis. Median was estimated using the Kaplan-Meier method. | up to 33 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First On-Study Skeletal-Related Event (Superiority) | Time to first on-study skeletal-related event (SRE) using a test for superiority. Median was estimated using the Kaplan-Meier method. | up to 33 months | 
| Time to the First-and-Subsequent On-Study Skeletal-Related Event | Time to the first-and-subsequent on-study skeletal-related event (SRE) using multiple event analysis. To be considered a subsequent SRE, the event must occur at least 21 days after the previous SRE. This outcome measure utilizes multiple event times, was analyzed based on a proportional mean model, and is therefore more appropriately summarized by the cumulative mean number of events. | up to 33 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bone metastases, lytic bone lesions, advanced cancer, multiple myeloma, lymphoma, solid tumors, skeletal related events, skeletal fractures, spinal cord compressions, radiation to bone, surgery to bone, bisphosphonates, denosumab