Study to Determine Treatment Effects of Denosumab in Patients With Breast Cancer Receiving Aromatase Inhibitor Therapy

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Austrian Breast and Colorectal Cancer Study Group
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00556374
First received: November 8, 2007
Last updated: January 23, 2014
Last verified: January 2014
  Purpose

The purpose of this study is to determine whether denosumab compared to placebo, will reduce the rate of first clinical fracture in women with non-metastatic breast cancer receiving (non-steroidal) aromatase inhibitor therapy.


Condition Intervention Phase
Breast Cancer
Drug: Placebo
Drug: Denosumab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: A Randomised, Double-Blind, Placebo-Controlled, Multi-Centre Phase 3 Study to Determine the Treatment Effect of Denosumab in Subjects With Non-Metastatic Breast Cancer Receiving Aromatase Inhibitor Therapy.

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • The time to the first clinical fracture. [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The incidence of new vertebral fractures at Months 12, 24 and 36 months /End of Treatment visit. [ Time Frame: Annually ] [ Designated as safety issue: No ]
  • The incidence of a new or worsening of pre-existing vertebral fractures at Months 12, 24 and 36 months/End of Treatment visit. [ Time Frame: Annually ] [ Designated as safety issue: No ]
  • The percentage change in total lumbar spine, total hip and femoral neck bone mineral bone density from baseline to 12, 24 and 36 months/End of Treatment visit (at pre-selected sites). [ Time Frame: Annually ] [ Designated as safety issue: No ]
  • Disease-free survival (DFS) [ Time Frame: Annually ] [ Designated as safety issue: No ]
    Disease-free survival is defined as any evidence of disease recurrence or death from any cause.

  • Bone metastasis-free survival (BMFS) [ Time Frame: Annually ] [ Designated as safety issue: No ]
    Bone metastasis-free survival determined by the time to first occurrence of bone metastasis (either symptomatic or asymptomatic) or death from any cause.

  • Overall survival (OS) [ Time Frame: Annually ] [ Designated as safety issue: No ]

Enrollment: 3425
Study Start Date: December 2006
Estimated Study Completion Date: October 2019
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Denosumab Drug: Denosumab
Patients will be randomized 1:1 to receive denosumab 60 mg or placebo sub-cutaneously every 6 months.
Placebo Comparator: Placebo Drug: Placebo
Patients will be randomized 1:1 to receive denosumab 60 mg or placebo sub-cutaneously every 6 months.

  Eligibility

Ages Eligible for Study:   45 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed adenocarcinoma of the breast;
  • Female subjects with non-metastatic disease who are estrogen receptor (ER) and/or progesterone receptor (PR) positive, and who have completed their treatment pathway;
  • Subjects who are currently on, or will initiate an approved non-steroidal aromatase inhibitor therapy (eg, anastrazole) in the adjuvant setting;
  • Postmenopausal woman, defined as a woman fulfilling any one of the following criteria:

    • Having undergone a bilateral oophorectomy;
    • Age ≥ 60 years;
    • Aged < 60 years meeting the following requirements:
  • FSH and estradiol in the postmenopausal range;
  • A negative pregnancy test within 7 days prior to randomization. Subjects who have undergone a hysterectomy do not require a pregnancy test.
  • More criteria may apply.

Exclusion Criteria:

  • Aromatase inhibitor therapy for more than 24 months;
  • Prior or concurrent treatment with Selective Estrogen Receptor Modulators (eg, tamoxifen);
  • Evidence of metastatic disease;
  • Current or prior IV bisphosphonate administration;
  • Oral bisphosphonate treatment greater than or equal to 3 years continuously OR greater than 3 months but less than 3 years unless there was a washout period of at least 1 year prior to randomization OR any use during the 3-month period prior to randomization;
  • Prior administration of denosumab;
  • Known liver or renal deficiency;
  • Recurrence of the primary malignancy (eg, during the allowed interval of pretreatment with aromatase inhibitor);
  • Diagnosis of any second non-breast malignancy within the last 5 years, except for adequately treated basal cell or squamous cell skin cancer, or for in situ carcinoma of the cervix uteri;
  • Any kind of disorder that compromises the ability to give written informed consent and/or comply with study procedures;
  • More criteria may apply.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00556374

  Show 47 Study Locations
Sponsors and Collaborators
Amgen
Austrian Breast and Colorectal Cancer Study Group
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00556374     History of Changes
Other Study ID Numbers: 20050209, ABCSG-18, 2005-005275-15
Study First Received: November 8, 2007
Last Updated: January 23, 2014
Health Authority: Austria: AGES - PharmaMed Austria Institut Wissenschaft & Information
Sweden:MPA :Medical Products Agency

Keywords provided by Amgen:
confirmed adenocarcinoma
non-metastatic breast cancer
estrogen receptor positive
progesterone receptor positive
non-steroidal aromatase
aromatase inhibitor therapy
postmenopausal woman
adjuvant chemotherapy
neoadjuvant chemotherapy

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 16, 2014