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: June 27, 2016
Last verified: June 2016
  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
Drug: Non-steroidal aromatase inhibitor therapy
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:
  • Time to First Clinical Fracture [ Time Frame: From randomization until the primary analysis cut-off date of 26 March 2014; maximum time on study was 87 months. ] [ Designated as safety issue: No ]
    The time to first on-study clinical fracture defined as the number of days from randomization to the date of the x-ray confirming the clinical fracture. A clinical fracture is any clinically evident fracture with associated symptoms and confirmed by x-ray. Participants who died or withdrew without experiencing a clinical fracture were censored at the date of last contact or study termination whichever was earlier.


Secondary Outcome Measures:
  • Percent Change From Baseline in Total Lumbar Spine Bone Mineral Density (BMD) at Month 36 at Pre-selected Sites [ Time Frame: Baseline and Month 36 ] [ Designated as safety issue: No ]
    Bone mineral density was assessed by dual x-ray absorptiometry.

  • Percent Change From Baseline in Total Hip BMD at Month 36 at Pre-selected Sites [ Time Frame: Baseline and Month 36 ] [ Designated as safety issue: No ]
    Bone mineral density was assessed by dual x-ray absorptiometry.

  • Percent Change From Baseline in Femoral Neck BMD at Month 36 at Pre-selected Sites [ Time Frame: Baseline and Month 36 ] [ Designated as safety issue: No ]
    Bone mineral density was assessed by dual x-ray absorptiometry.

  • Number of Participants With New Vertebral Fractures [ Time Frame: 36 months ] [ Designated as safety issue: No ]

    Assessment of vertebral fractures was performed by an expert radiologist at the central imaging center using a semiquantitative grading scale: Grade 1, 20% to 25% reduction in vertebral height (anterior, middle, or posterior); Grade 2, 25% to 40% reduction in height; Grade 3, greater than 40% reduction in height.

    A new vertebral fracture is defined as a fracture in a previously undeformed vertebrae including new compression fractures, defined as those compression fractures having a decrease in total anterior or posterior height of at least 25% from baseline. New vertebral fractures includes morphometric vertebral fractures identified from on study x-rays and clinical vertebral fractures confirmed by x-rays.


  • Number of Participants With New or Worsening Vertebral Fractures [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    Assessment of vertebral fractures was performed by an expert radiologist at the central imaging center using a semiquantitative grading scale: Grade 1, 20% to 25% reduction in vertebral height (anterior, middle, or posterior); Grade 2, 25% to 40% reduction in height; Grade 3, greater than 40% reduction in height. A new vertebral fracture is defined as a fracture in a previously undeformed vertebrae including new compression fractures, defined as those compression fractures having a decrease in total anterior or posterior height of at least 25% from baseline. New vertebral fractures includes morphometric vertebral fractures identified from on study x-rays and clinical vertebral fractures confirmed by x-rays. Worsening of pre-existing fractures is defined as an increase in fracture severity of at least 1 grade on the semiquantitative scale.

  • Disease-free Survival [ Time Frame: Participants will be followed for disease-free survival (DFS) once every 12 months for 66 months after primary completion date. ] [ Designated as safety issue: No ]
    Disease-free survival (DFS) determined by the time from randomization to the first observation of disease recurrence or death from any cause. DFS will be analyzed after long-term follow-up is complete.

  • Bone Metastases-free Survival [ Time Frame: Participants will be followed for bone metastasis-free survival once every 12 months for 66 months after primary completion date. ] [ Designated as safety issue: No ]
    Bone metastasis-free survival (BMFS) determined by the time from randomization to the first observation of bone metastasis or death from any cause. BMFS will be analyzed after long-term follow-up is complete.

  • Overall Survival [ Time Frame: Participants will be followed for overall survival once every 12 months for 66 months after primary completion date. ] [ Designated as safety issue: No ]
    Overall survival (OS) determined by the time from randomization to death from any cause. OS will be analyzed after long-term follow-up is complete.


Enrollment: 3420
Study Start Date: December 2006
Estimated Study Completion Date: October 2019
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Denosumab
Participants received 60 mg denosumab subcutaneous injection once every 6 months. All participants continued to receive an approved non-steroidal aromatase inhibitor therapy.
Drug: Denosumab Drug: Non-steroidal aromatase inhibitor therapy
An approved non-steroidal aromatase inhibitor therapy (eg, anastrazole) in the adjuvant setting
Placebo Comparator: Placebo
Participants received placebo subcutaneous injection once every 6 months. All participants continued to receive an approved non-steroidal aromatase inhibitor therapy.
Drug: Placebo Drug: Non-steroidal aromatase inhibitor therapy
An approved non-steroidal aromatase inhibitor therapy (eg, anastrazole) in the adjuvant setting

  Eligibility

Ages Eligible for Study:   45 Years to 100 Years   (Adult, Senior)
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:
  • Follicle-stimulating hormone (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 intravenous (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 (e.g., 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:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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
Results First Received: October 6, 2015
Last Updated: June 27, 2016
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
Denosumab
Aromatase Inhibitors
Bone Density Conservation Agents
Physiological Effects of Drugs
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on July 26, 2016