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
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: 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 September 29, 2014