Denosumab (AMG 162) in Bisphosphonate Naive Metastatic Breast Cancer

Breast Cancer Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00091832
• Other study ID #: 20040113
• Status: Completed
• Phase: Phase 2
• First received: September 17, 2004
• Last updated: December 20, 2013
• Start date: September 2004
• Est. completion date: October 2006

Study information

• Verified date: December 2013
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Human Research Ethics CommitteeAustralia: Therapeutic Goods AdministrationAustria: AGES - PharmaMed Austria Institut Wissenschaft & InformationAustria: Bundesamt fur Sicherheit im GesundheitswesenAustria: Bundesamt für Sicherheit im GesundheitswesenAustria: Central Ethics CommitteeAustria: Competant AuthorityAustria: Secretariat of HealthBelgium: Federal Agency for Medicines and Health Products, FAMHPBelgium: Directorate-General for Medicinal ProductsBelgium: Federal Public Service (FPS) Health, Food Chain Safety and EnvironmentBelgium: FPS of Public Health, Food Chain Security and EnvironmentBelgium: Pharmaceutical InspectorateAustralia: Department of Health and Ageing Therapeutic Goods AdministrationCanada: Health CanadaCanada: Health Products and Food BranchCanada: Institutional Review BoardEuropean Union: European Medicines AgencyFrance and Sweden: European Medicines AgencyFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)France: CCPPRB Central Ethics CommitteeFrance: Ministry of HealthGermany: Federal Institute for Drugs and Medical DevicesItaly: Local Ethics CommitteesItaly: Ministry of HealthMexico: COFEPRISMexico: Ministry of HealthBelgium: Service Public Federal Sante Publiquest, Securite de la Chaine alimentaire et EnvironnementBelgium: Service Public Fédéral Santé Publique, Sécurité de la Chaîne alimentaire et EnvironnementMexico: SSA (Secretaria de Salud Publica)Portugal: National Institute of Pharmacy and MedicinesSpain: Agencia Española de Medicamentos y Productos SanitariosSpain: Spanish Agency of MedicinesSpain: Spanish Drug AgencyUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 255
• Est. completion date: October 2006
• Est. primary completion date: November 2005
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria: - Histologically or cytologically confirmed breast adenocarcinoma

• At least one bone metastasis

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

Related Conditions & MeSH terms

• Bone Marrow Diseases
• Bone Metastases in Subjects With Advanced Breast Cancer
• Bone Neoplasms
• Breast Cancer
• Breast Neoplasms
• Metastases
• Neoplasm Metastasis

Intervention

Biological:
• Denosumab
Denosumab administered by subcutaneous injection

Drug:
• IV Bisphosphonates
Commercially available intravenous (IV) bisphosphonates administered per package insert, included pamidronate, ibandronic acid, and zoledronic acid

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

References & Publications (4)

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 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. Epub 2007 Sep 4. — View Citation

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. — View Citation

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;

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	Yes

External Links

•   AmgenTrials clinical trials website