Denosumab (AMG 162) in Bisphosphonate Naive Metastatic Breast Cancer

Study Overview
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Brief Summary
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This study is to evaluate various doses and schedules for denosumab administration and characterize the safety profile in this indication.

Official Title
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A Randomized Active-controlled Study of AMG 162 in Breast Cancer Subjects With Bone Metastasis Who Have Not Previously Been Treated With Bisphosphonate Therapy.

Conditions
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Breast Cancer, Metastases, Bone Metastases in Subjects With Advanced Breast Cancer

Intervention / Treatment
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* Biological: Denosumab
* Drug: IV Bisphosphonates


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Histologically or cytologically confirmed breast adenocarcinoma At least one bone metastasis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Denosumab 60 mg every 12 weeks<br>Denosumab 60 mg by subcutaneous injection once every 12 weeks (Q12W) for 25 weeks. | Biological: Denosumab<br>* Denosumab administered by subcutaneous injection<br>* Other names: AMG 162;|
| Experimental: Denosumab 120 mg every 4 weeks<br>Denosumab 120 mg by subcutaneous injection once every 4 weeks (Q4W) for 25 weeks. | Biological: Denosumab<br>* Denosumab administered by subcutaneous injection<br>* Other names: AMG 162;|
| Experimental: Denosumab 180 mg every 4 weeks<br>Denosumab 180 mg by subcutaneous injection once every 4 weeks (Q4W) for 25 weeks. | Biological: Denosumab<br>* Denosumab administered by subcutaneous injection<br>* Other names: AMG 162;|
| Active Comparator: IV bisphosphonates every 4 weeks<br>Open label bisphosphonate every 4 weeks (Q4W) by intravenous infusion for 25 weeks. | Drug: IV Bisphosphonates<br>* Commercially available intravenous (IV) bisphosphonates administered per package insert, included pamidronate, ibandronic acid, and zoledronic acid<br>|
| Experimental: Denosumab 180 mg every 12 weeks<br>Denosumab 180 mg by subcutaneous injection once every 12 weeks (Q12W) for 25 weeks. | Biological: Denosumab<br>* Denosumab administered by subcutaneous injection<br>* Other names: AMG 162;|
| Experimental: Denosumab 30 mg every 4 weeks<br>Denosumab 30 mg by subcutaneous injection once every 4 weeks (Q4W) for 25 weeks. | Biological: Denosumab<br>* Denosumab administered by subcutaneous injection<br>* Other names: AMG 162;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline to Week 13 in Creatinine-adjusted Urinary N-telopeptide (uNTx/Cr) | Percent change from Baseline to Week 13 in Urinary N-telopeptide corrected by creatinine (uNTx/Cr) calculated using ((Week 13 value - Baseline value) / Baseline value ) x 100. | Baseline and Week 13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline to Week 25 in Urinary N-telopeptide (uNTx) | Percent change from Baseline to Week 25 in Urinary N-telopeptide (uNTx) calculated using ((Week 25 value - Baseline value) / Baseline value) x 100. | Baseline and Week 25 | 
| Number of Participants Achieving 65% or More Reduction in Urinary N-telopeptide (uNTx) From Baseline at Week 13 | The number of participants achieving a 65% reduction or more in uNTx from Baseline at Week 13. Calculation used is ((Week 13 value - Baseline value) / Baseline value ) x 100 and participants were considered having a 65% reduction or more if their value was ≤ -65%. | Baseline and Week 13 | 
| Number of Participants Achieving 65% or More Reduction in uNTX From Baseline at Week 25 | The number of participants achieving a 65% reduction or more in uNTX from Baseline at Week 25. Calculation used is ((Week 25 value - Baseline value) / Baseline value) x 100 and participants were considered having a 65% reduction or more if their value was ≤ -65%. | Baseline and Week 25 | 
| Time to 65% or More Reduction in Urinary N-telopeptide (uNTX) From Baseline | Kaplan-Meier estimate of the median time from enrollment to the first occurrence of a reduction of uNTx of ≥ 65% compared to Baseline. For participants whose uNTx did not fall below 65% of the Baseline value, the time was censored at time of last evaluation of uNTx. | Baseline to Week 57 | 
| Percent Change From Baseline to Week 13 in Serum C-Telopeptide (CTX) | Percent change from Baseline to Week 13 in type I serum C-telopeptide (CTX) calculated using ((Week 13 value - Baseline value) / Baseline value) x 100. | Baseline and week 13 | 
| Percent Change From Baseline to Week 25 in Serum C-telopeptide (CTX) | Percent change from Baseline to Week 25 in type I serum C-telopeptide calculated using ((Week 25 value - Baseline value) / Baseline value) x 100. | Baseline and Week 25 | 
| Percent Change From Baseline to Week 13 in Procollagen I N-terminal Peptide (P1NP) | Percent change from Baseline to Week 13 in procollagen 1 N-terminal peptide calculated using ((Week 13 value - Baseline value) / Baseline value) x 100. | Baseline and Week 13 | 
| Percent Change From Baseline to Week 25 in P1NP | Percent change from Baseline to Week 25 in procollagen 1 N-terminal peptide (P1NP) calculated using ((Week 25 value - Baseline value) / Baseline value ) x 100. | Baseline and Week 25 | 
| Percent Change From Baseline to Week 13 in Tartrate-resistant Acid Phosphatase 5b (TRAP5b) | Percent change from Baseline to Week 13 in tartrate-resistant acid phosphatase 5b calculated using ((Week 13 value - Baseline value) / Baseline value) x 100. | Baseline and Week 13 | 
| Percent Change From Baseline to Week 25 in Tartrate-resistant Acid Phosphatase 5b (TRAP5b) | Percent change from Baseline to Week 25 in TRAP5b calculated using ((Week 25 value - Baseline value) / Baseline value) x 100. | Baseline and Week 25 | 
| Percent Change From Baseline to Week 13 in Bone Specific Alkaline Phosphatase (BSAP) | Percent change from Baseline to Week 13 in bone specific alkaline phosphatase (BSAP) calculated using ((Week 13 value - Baseline value) / Baseline value) x 100. | Baseline and Week 13 | 
| Percent Change From Baseline to Week 25 in Bone Specific Alkaline Phosphatase (BSAP) | Percent change from Baseline to Week 25 in BSAP calculated using ((Week 25 value - Baseline value) / Baseline value) x 100. | Baseline and Week 25 | 
| Percent Change From Baseline to Week 13 in Osteocalcin | Percent change from Baseline to Week 13 in osteocalcin calculated using ((Week 13 value - Baseline value) / Baseline value ) x 100. | Baseline and Week 13 | 
| Percent Change From Baseline to Week 25 in Osteocalcin | Percent change from Baseline to Week 25 in osteocalcin calculated using ((Week 25 value - Baseline value) / Baseline value) x 100. | Baseline and Week 25 | 
| Time to First Skeletal Related Event | Skeletal Related Event (SRE) defined as ≥ 1 of the following: pathological bone fracture, spinal cord compression, surgery or radiation therapy to bone (including the use of radioisotopes). | Day 1 to Week 25 | 
| Number of Participants With Skeletal Related Events | Skeletal Related Events (SRE) are defined as ≥ 1 of the following: pathological bone fracture, spinal cord compression, surgery or radiation therapy to bone (including the use of radioisotopes). | From Day 1 to Week 25 | 
| Number of Participants With Hypercalcemia | Occurrence of grade 3 or 4 hypercalcemia according to the Common Terminology Criteria for Adverse Events (CTCAE) v3. A summary of hypercalcemia events is reported under adverse events. | Day 1 to Week 57 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer, Cancer