Bone Mineral Density in Postmenopausal Women at Increased Risk of Developing Breast Cancer And Who Are Receiving Exemestane on Clinical Trial CAN-NCIC-MAP3

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00688246
First received: May 30, 2008
Last updated: November 11, 2013
Last verified: July 2012
  Purpose

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.


Condition Intervention
Breast Cancer
Osteoporosis
Other: biologic sample preservation procedure
Procedure: dual x-ray absorptometry

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Influence of Five Years of Exemestane on Bone Mineral Density in Postmenopausal Women at Increased Risk of Developing Breast Cancer

Resource links provided by NLM:


Further study details as provided by NCIC Clinical Trials Group:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Changes in markers of bone formation and resorption 1 and 5 years after randomization on CAN-NCIC-MAP3 [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Number of clinical skeletal fractures by radiology report [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Serum


Enrollment: 238
Study Start Date: January 2008
Study Completion Date: January 2013
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Other: biologic sample preservation procedure
    Increased bone turnover may be a risk factor for fracture [Lønning 2005]. However, it is uncertain whether markers of bone resorption and markers of bone formation are both associated with fracture risk [Looker 2000]. Therefore, we will measure bone formation and bone resorption markers at baseline, year 1 and year 5. Blood specimens will be shipped to and stored in a central laboratory for future assays of bone biomarkers. For markers of bone formation, the N-terminal Propeptide of Type I Collagen (PINP) will be measured. For bone resorption markers, serum levels of cross-linked N-telopeptides of type I collagen (NTx) will be measured. Note: Subjects must fast 12-14 hours prior to blood draw.
    Procedure: dual x-ray absorptometry
    BMD of the spine (L1-L4) and total hip will be done within 12 months prior to randomization to the MAP.3 core protocol. BMD by DEXA of the spine (L1-L4) and total hip will be repeated at year 2 and year 5 of the MAP.3 core study on the same Lunar or Hologic scanner.
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.

  Eligibility

Ages Eligible for Study:   35 Years and older
Genders Eligible for Study:   Female
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

Criteria

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
  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: NCT00688246

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

Additional Information:
No publications provided

Responsible Party: NCIC Clinical Trials Group
ClinicalTrials.gov Identifier: NCT00688246     History of Changes
Other Study ID Numbers: MAP3B, CAN-NCIC-MAP3B, PFIZER-NCIC-MAP3B, CDR0000586285
Study First Received: May 30, 2008
Last Updated: November 11, 2013
Health Authority: Canada: NCIC Clinical Trials Group
United States: Food and Drug Administration

Keywords provided by NCIC Clinical Trials Group:
osteoporosis
breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Osteoporosis
Bone Diseases
Bone Diseases, Metabolic
Breast Diseases
Musculoskeletal Diseases
Neoplasms
Neoplasms by Site
Skin Diseases

ClinicalTrials.gov processed this record on October 30, 2014