Denosumab (AMG 162) in Bisphosphonate Naive Metastatic Breast Cancer

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

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

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Metastases; Bone Metastases in Subjects With Advanced Breast Cancer
• Intervention / Treatment: Biological: Denosumab; Drug: IV Bisphosphonates

• Study Type: Interventional
• Enrollment (Actual): 255
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria: - Histologically or cytologically confirmed breast adenocarcinoma

• At least one bone metastasis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• Campbell-Baird C, Lipton A, Sarkenshik M, Ma H, Jun S.Incidence of Acute Phase Events Following Denosumab or Intravenous Bisphosphonates: Results From a Randomized, Controlled Phase 2 Study in Patients With Breast Cancer and Bone Metastases.Journal-001752;2010;7:85-89.
• Lipton A, Steger GG, Figueroa J, Alvarado C, Solal-Celigny P, Body JJ, de Boer R, Berardi R, Gascon P, Tonkin KS, Coleman RE, Paterson AH, Gao GM, Kinsey AC, Peterson MC, Jun S. Extended efficacy and safety of denosumab in breast cancer patients with bone metastases not receiving prior bisphosphonate therapy. Clin Cancer Res. 2008 Oct 15;14(20):6690-6. doi: 10.1158/1078-0432.CCR-07-5234.
• Lipton A, Steger GG, Figueroa J, Alvarado C, Solal-Celigny P, Body JJ, de Boer R, Berardi R, Gascon P, Tonkin KS, Coleman R, Paterson AH, Peterson MC, Fan M, Kinsey A, Jun S. Randomized active-controlled phase II study of denosumab efficacy and safety in patients with breast cancer-related bone metastases. J Clin Oncol. 2007 Oct 1;25(28):4431-7. doi: 10.1200/JCO.2007.11.8604. Epub 2007 Sep 4.
• Peterson M, Rodriquez R., Gurrola E., Sohn W, Jun S (others??).Population pharmacokinetics and pharmacodynamics of denosumab in breast cancer patients with bone metastases.Journal-000709;

Helpful Links

• AmgenTrials clinical trials website
• Notice regarding posted summaries of trial results

Study record dates

Study Major Dates

• Study Start: September 1, 2004
• Primary Completion (Actual): November 1, 2005
• Study Completion (Actual): October 1, 2006

Study Registration Dates

• First Submitted: September 17, 2004
• First Submitted That Met QC Criteria: September 20, 2004
• First Posted (Estimate): September 21, 2004

Study Record Updates

• Last Update Posted (Estimate): January 28, 2014
• Last Update Submitted That Met QC Criteria: December 20, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Keywords: Breast Cancer; Cancer
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Neoplastic Processes; Breast Neoplasms; Neoplasm Metastasis; Neoplasms, Second Primary; Physiological Effects of Drugs; Bone Density Conservation Agents; Denosumab; Diphosphonates
• Other Study ID Numbers: 20040113