Bone Mineral Density in Postmenopausal Women at Increased Risk of Breast Cancer And Who Are Receiving Exemestane on MAP3

August 3, 2023 updated by: NCIC Clinical Trials Group

The Influence of Five Years of Exemestane on Bone Mineral Density in Postmenopausal Women at Increased Risk of Developing Breast Cancer

RATIONALE: Learning about the effect of exemestane on bone mineral density in postmenopausal women at increased risk of breast cancer may help plan treatment, decrease the risk of broken bones, and help patients live more comfortably.

PURPOSE: This research study is measuring bone mineral density in postmenopausal women at increased risk of developing breast cancer who are receiving exemestane on clinical trial CAN-NCIC-MAP3.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

To assess the percentage change in bone mineral density (BMD) as measured by dual x-ray absorptometry (DEXA) scans of the spine (L1-L4) and total hip 2 years after randomization (and registration to the MAP.3B protocol).

Secondary

To assess the percentage change in BMD as measured by DEXA scans of the spine (L1-L4), and total hip 5 years after randomization (and registration to the MAP.3B protocol).
To compare the proportion of women who develop BMD of the spine (L1-L4) and total hip below the absolute threshold value for osteoporosis (T score ≤ -2.5 SD below the mean peak bone mass in young women) in the treatment groups.
To examine the pattern of changes in BMD parameters and bone biomarkers (i.e., PINP and NTx) over time and the impact of covariants using exploratory longitudinal analyses.
To compare the proportion of women who develop clinical skeletal fractures in the treatment groups.

OUTLINE: Patients undergo bone mineral density (BMD) measurement by dual x-ray absorptometry (DEXA). Blood specimens are collected at baseline and at 1 year, and 5 years and stored in a central laboratory for future assays of the bone biomarkers.

If the subject withdraws from the core MAP.3 study before 5 years, a bone density measurement and serum for bone biomarkers is obtained unless performed within the past 3 months. Patients may continue to be followed on the MAP.3 core study for fractures (and other MAP.3 study endpoints) for a minimum of 5 years after randomization.

Study Type

Observational

Enrollment (Actual)

238

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Canada
- British Columbia
  - Kelowna, British Columbia, Canada, V1Y 5L3
    - BCCA - Cancer Centre for the Southern Interior
  - Vancouver, British Columbia, Canada, V5Z 4E6
    - BCCA - Vancouver Cancer Centre
- Ontario
  - London, Ontario, Canada, N6A 4L6
    - London Regional Cancer Program
  - Sudbury, Ontario, Canada, P3E 5J1
    - Northeast Cancer Center Health Sciences
  - Toronto, Ontario, Canada, M5G 2M9
    - Univ. Health Network-Princess Margaret Hospital
United States
- California
  - Torrance, California, United States, 90502
    - Los Angeles Biomedical Research Institute
- District of Columbia
  - Washington, District of Columbia, United States, 20037
    - The George Washington University
- Maine
  - Scarborough, Maine, United States, 04074-9308
    - Maine Center for Cancer Medicine and Blood Disorders
- Maryland
  - Bethesda, Maryland, United States, 20817
    - Suburban Hospital Cancer Program
- Massachusetts
  - Boston, Massachusetts, United States, 02115
    - Dana-Farber Cancer Institute
  - Boston, Massachusetts, United States, 02114
    - Massachusetts General Hospital
- Michigan
  - Detroit, Michigan, United States, 48201
    - Hutzel Women's Health Specialists
- New Jersey
  - Newark, New Jersey, United States, 07107
    - University of Medicine and Dentistry of New Jersey
- Oklahoma
  - Oklahoma City, Oklahoma, United States, 73104
    - University of Oklahoma
- Rhode Island
  - Pawtucket, Rhode Island, United States, 02860
    - The Memorial Hospital of Rhode Island
- Vermont
  - Burlington, Vermont, United States, 05401
    - Fletcher Allen Health Care
- Washington
  - Seattle, Washington, United States, 98109-1024
    - Fred Hutchinson Cancer Research Center
- Wisconsin
  - Madison, Wisconsin, United States, 53715
    - Univ. of Wisconsin Center for Women's Health and

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

35 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Eligible women consenting to be randomized to the core MAP.3 trial will be approached for participation in this companion study. They must have an acceptable quality BMD scan by DEXA taken within 12 months prior to randomization to MAP.3. A BMD T-score > -2.0 SD (i.e. 2.0 standard deviations below the average peak BMD of a young adult woman) has been established as the study population cut-off because postmenopausal women who have BMD T-scores as low as or lower than - 2.0 SD are currently recommended to consider pharmacological therapies for their bones

Description

DISEASE CHARACTERISTICS:

At increased risk of developing breast cancer and enrolled on clinical trial CAN-NCIC-MAP3
Bone mineral density (BMD) (as measured by dual x-ray absorptometry [DEXA] scans within 12 months prior to randomization to the core protocol [MAP.3]) T score > -2.0 standard deviation (i.e., 2.0 standard deviations below the average peak BMD of a young adult woman) of spine (L1-L4) and total hip
Serum for bone biomarkers (i.e., serum N-telopeptide and serum amino-terminal procollagen 1 extension peptide) must have been obtained within 8 weeks prior to registration to the study

PATIENT CHARACTERISTICS:

Postmenopausal, defined as one of the following:
- Over 50 years of age with no spontaneous menses for at least 12 months before study entry
- 50 years of age or under with no menses (spontaneous or secondary to hysterectomy) for at least 12 months before study entry AND with follicle-stimulating hormone level within postmenopausal range
- Underwent prior bilateral oophorectomy
Available for collection of serum samples and BMD (DEXA) scans at the protocol defined times (i.e., have BMD scans at years 2 and 5 at the same site)
No history of fragility fractures (i.e., a broken bone that occurs with a fall from a standing height or lesser amount of trauma)
No malabsorption syndrome (e.g., untreated celiac disease, clinically relevant vitamin D deficiency, or active hyper- or hypoparathyroidism)
No Paget disease or other metabolic bone diseases (e.g., osteomalacia or osteogenesis imperfecta)
No Cushing disease or other pituitary diseases
No inflammatory disease(s) (e.g., inflammatory bowel disease, rheumatoid arthritis, lupus, psoriasic arthritis, ankylosing spondylitis, or autoimmune hepatitis)

PRIOR CONCURRENT THERAPY:

More than 3 months since prior bone drugs, such as bisphosphonates, teriparatide (parathyroid hormone [PTH]), sodium fluoride, calcitonin (Miacalcin®), strontium, or high-dose vitamin D (i.e., vitamin D3 > 2,000 IU/day or calcitriol)
No prior bisphosphonate therapy duration of more than 6 months total during lifetime
No concurrent anabolic or chronic oral corticosteroids (the equivalent of 5 mg of prednisone a day or higher for more than 2 weeks within the past 6 months and will likely require ongoing therapy)
Concurrent inhaled steroids allowed
No concurrent medication that may have an effect on study endpoints for this study, including any of the following:
- Anticonvulsants
- Sodium fluoride at daily doses > 5 mg/day for a period exceeding 1 month
- Anabolic steroids
- Teriparatide (parathyroid hormone)
- Bisphosphonates, except for women who develop osteoporosis while on this study; these patients may be advised to start bone medication (i.e., strontium, calcitonin, or high-dose Vitamin D (i.e., Vitamin D3 > 2000 IU/day or calcitriol) at the discretion of their physician

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in bone mineral density (BMD) as measured by dual x-ray absorptometry (DEXA) scans of the spine (L1-L4) and total hip 2 years after randomization Time Frame: 2 years	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in BMD as measured by DEXA scans of the spine (L1-L4) and total hip 5 years after randomization on CAN-NCIC-MAP3 Time Frame: 5 years	5 years
Changes in markers of bone formation and resorption 1 and 5 years after randomization on CAN-NCIC-MAP3 Time Frame: 5 years	5 years
Development of osteoporosis either by sustaining a fragility fracture or by having a BMD T-score at or lower than - 2.5 SD at the spine (L1-L4) or total hip Time Frame: 2 years	2 years
Number of clinical skeletal fractures by radiology report Time Frame: 2 years	2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NCIC Clinical Trials Group

Investigators

Study Chair: Paul E. Goss, MD, PhD, Massachusetts General Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 10, 2008

Primary Completion (Actual)

October 31, 2011

Study Completion (Actual)

January 10, 2013

Study Registration Dates

First Submitted

May 30, 2008

First Submitted That Met QC Criteria