Denosumab (AMG 162) in Bisphosphonate Naive Metastatic Breast Cancer

Phase 2

Completed

• Conditions: Breast Cancer; Bone Metastases in Subjects With Advanced Breast Cancer; Metastases
• Interventions: Biological: Denosumab; Drug: IV Bisphosphonates

• Registration Number: NCT00091832
• Lead Sponsor: Amgen

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study Start: 2004-09
• Study First Submitted: 2004-09-17
• Study First Submitted QC: 2004-09-20
• Study First Posted: 2004-09-21
• Primary Completion: 2005-11
• Study Completion: 2006-10
• Disposition First Submitted: 2009-11-23
• Disposition First Submitted QC: 2009-11-23
• Disposition First Posted: 2009-11-25
• Results First Submitted: 2010-12-09
• Results First Submitted QC: 2010-12-09
• Results First Posted: 2011-01-07
• Status Verified: 2013-12
• Last Update Submitted: 2013-12-20
• Last Update Posted: 2014-01-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 255

Inclusion Criteria

• Histologically or cytologically confirmed breast adenocarcinoma

• At least one bone metastasis

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Denosumab 60 mg every 12 weeks	Denosumab	Denosumab 60 mg by subcutaneous injection once every 12 weeks (Q12W) for 25 weeks.
Denosumab 120 mg every 4 weeks	Denosumab	Denosumab 120 mg by subcutaneous injection once every 4 weeks (Q4W) for 25 weeks.
Denosumab 180 mg every 4 weeks	Denosumab	Denosumab 180 mg by subcutaneous injection once every 4 weeks (Q4W) for 25 weeks.
IV bisphosphonates every 4 weeks	IV Bisphosphonates	Open label bisphosphonate every 4 weeks (Q4W) by intravenous infusion for 25 weeks.
Denosumab 180 mg every 12 weeks	Denosumab	Denosumab 180 mg by subcutaneous injection once every 12 weeks (Q12W) for 25 weeks.
Denosumab 30 mg every 4 weeks	Denosumab	Denosumab 30 mg by subcutaneous injection once every 4 weeks (Q4W) for 25 weeks.

Primary Outcome Measures

Name	Time	Method
Percent Change From Baseline to Week 13 in Creatinine-adjusted Urinary N-telopeptide (uNTx/Cr)	Baseline and Week 13	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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants Achieving 65% or More Reduction in Urinary N-telopeptide (uNTx) From Baseline at Week 13	Baseline and 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%.
Percent Change From Baseline to Week 25 in Urinary N-telopeptide (uNTx)	Baseline and Week 25	Percent change from Baseline to Week 25 in Urinary N-telopeptide (uNTx) calculated using ((Week 25 value - Baseline value) / Baseline value) x 100.
Number of Participants Achieving 65% or More Reduction in uNTX From Baseline at Week 25	Baseline and 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%.
Time to 65% or More Reduction in Urinary N-telopeptide (uNTX) From Baseline	Baseline to Week 57	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.
Percent Change From Baseline to Week 13 in Serum C-Telopeptide (CTX)	Baseline and week 13	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.
Percent Change From Baseline to Week 25 in Serum C-telopeptide (CTX)	Baseline and Week 25	Percent change from Baseline to Week 25 in type I serum C-telopeptide calculated using ((Week 25 value - Baseline value) / Baseline value) x 100.
Percent Change From Baseline to Week 13 in Procollagen I N-terminal Peptide (P1NP)	Baseline and Week 13	Percent change from Baseline to Week 13 in procollagen 1 N-terminal peptide calculated using ((Week 13 value - Baseline value) / Baseline value) x 100.
Percent Change From Baseline to Week 25 in P1NP	Baseline and Week 25	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.
Percent Change From Baseline to Week 13 in Tartrate-resistant Acid Phosphatase 5b (TRAP5b)	Baseline and Week 13	Percent change from Baseline to Week 13 in tartrate-resistant acid phosphatase 5b calculated using ((Week 13 value - Baseline value) / Baseline value) x 100.
Percent Change From Baseline to Week 25 in Tartrate-resistant Acid Phosphatase 5b (TRAP5b)	Baseline and Week 25	Percent change from Baseline to Week 25 in TRAP5b calculated using ((Week 25 value - Baseline value) / Baseline value) x 100.
Percent Change From Baseline to Week 13 in Bone Specific Alkaline Phosphatase (BSAP)	Baseline and Week 13	Percent change from Baseline to Week 13 in bone specific alkaline phosphatase (BSAP) calculated using ((Week 13 value - Baseline value) / Baseline value) x 100.
Percent Change From Baseline to Week 25 in Bone Specific Alkaline Phosphatase (BSAP)	Baseline and Week 25	Percent change from Baseline to Week 25 in BSAP calculated using ((Week 25 value - Baseline value) / Baseline value) x 100.
Percent Change From Baseline to Week 13 in Osteocalcin	Baseline and Week 13	Percent change from Baseline to Week 13 in osteocalcin calculated using ((Week 13 value - Baseline value) / Baseline value ) x 100.
Percent Change From Baseline to Week 25 in Osteocalcin	Baseline and Week 25	Percent change from Baseline to Week 25 in osteocalcin calculated using ((Week 25 value - Baseline value) / Baseline value) x 100.
Time to First Skeletal Related Event	Day 1 to Week 25	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).
Number of Participants With Skeletal Related Events	From Day 1 to Week 25	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).
Number of Participants With Hypercalcemia	Day 1 to Week 57	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.