Denosumab (AMG 162) in Bisphosphonate Naive Metastatic Breast Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00091832
First received: September 17, 2004
Last updated: December 20, 2013
Last verified: December 2013
  Purpose

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


Condition Intervention Phase
Breast Cancer
Metastases
Bone Metastases in Subjects With Advanced Breast Cancer
Biological: Denosumab
Drug: IV Bisphosphonates
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: A Randomized Active-controlled Study of AMG 162 in Breast Cancer Subjects With Bone Metastasis Who Have Not Previously Been Treated With Bisphosphonate Therapy.

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Percent Change From Baseline to Week 13 in Creatinine-adjusted Urinary N-telopeptide (uNTx/Cr) [ Time Frame: Baseline and Week 13 ] [ Designated as safety issue: No ]
    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:
  • Percent Change From Baseline to Week 25 in Urinary N-telopeptide (uNTx) [ Time Frame: Baseline and Week 25 ] [ Designated as safety issue: No ]
    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 Urinary N-telopeptide (uNTx) From Baseline at Week 13 [ Time Frame: Baseline and Week 13 ] [ Designated as safety issue: No ]
    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%.

  • Number of Participants Achieving 65% or More Reduction in uNTX From Baseline at Week 25 [ Time Frame: Baseline and Week 25 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline to Week 57 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline and week 13 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline and Week 25 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline and Week 13 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Week 25 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline and Week 13 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline and Week 25 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline and Week 13 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline and Week 25 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Week 13 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Week 25 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 to Week 25 ] [ Designated as safety issue: No ]
    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 [ Time Frame: From Day 1 to Week 25 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 to Week 57 ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 255
Study Start Date: September 2004
Study Completion Date: October 2006
Primary Completion Date: November 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: 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 Name: 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 Name: AMG 162

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria: - Histologically or cytologically confirmed breast adenocarcinoma

  • At least one bone metastasis
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00091832

Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
Publications:
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00091832     History of Changes
Other Study ID Numbers: 20040113
Study First Received: September 17, 2004
Results First Received: December 9, 2010
Last Updated: December 20, 2013
Health Authority: Australia: Human Research Ethics Committee
Australia: Therapeutic Goods Administration
Austria: AGES - PharmaMed Austria Institut Wissenschaft & Information
Austria: Bundesamt fur Sicherheit im Gesundheitswesen
Austria: Bundesamt für Sicherheit im Gesundheitswesen
Austria: Central Ethics Committee
Austria: Competant Authority
Austria: Secretariat of Health
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Belgium: Directorate-General for Medicinal Products
Belgium: Federal Public Service (FPS) Health, Food Chain Safety and Environment
Belgium: FPS of Public Health, Food Chain Security and Environment
Belgium: Pharmaceutical Inspectorate
Australia: Department of Health and Ageing Therapeutic Goods Administration
Canada: Health Canada
Canada: Health Products and Food Branch
Canada: Institutional Review Board
European Union: European Medicines Agency
France and Sweden: European Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: CCPPRB Central Ethics Committee
France: Ministry of Health
Germany: Federal Institute for Drugs and Medical Devices
Italy: Local Ethics Committees
Italy: Ministry of Health
Mexico: COFEPRIS
Mexico: Ministry of Health
Belgium: Service Public Federal Sante Publiquest, Securite de la Chaine alimentaire et Environnement
Belgium: Service Public Fédéral Santé Publique, Sécurité de la Chaîne alimentaire et Environnement
Mexico: SSA (Secretaria de Salud Publica)
Portugal: National Institute of Pharmacy and Medicines
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Spain: Spanish Agency of Medicines
Spain: Spanish Drug Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Amgen:
Breast Cancer
Cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasm Metastasis
Neoplasms, Second Primary
Bone Neoplasms
Bone Marrow Diseases
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplastic Processes
Pathologic Processes
Bone Diseases
Musculoskeletal Diseases
Hematologic Diseases
Diphosphonates
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 26, 2014