Clinical trial NCT00688246: Bone Mineral Density in Postmenopausal Women at Increased Risk of Breast Cancer And Who Are Receiving Exemestane on MAP3
Official title: The Influence of Five Years of Exemestane on Bone Mineral Density in Postmenopausal Women at Increased Risk of Developing Breast Cancer
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Breast Cancer
Osteoporosis
Keywords: osteoporosis
breast cancer
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
First posted: 2008-06-02
Enrollment: 238
Sex: FEMALE
Minimum age (years): 35
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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

Brief summary: 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.

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 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

Primary outcomes:
measure: 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
timeFrame: 2 years
Secondary outcomes:
measure: Change in BMD as measured by DEXA scans of the spine (L1-L4) and total hip 5 years after randomization on CAN-NCIC-MAP3
timeFrame: 5 years
measure: Changes in markers of bone formation and resorption 1 and 5 years after randomization on CAN-NCIC-MAP3
timeFrame: 5 years
measure: 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
timeFrame: 2 years
measure: Number of clinical skeletal fractures by radiology report
timeFrame: 2 years
Other outcomes:
Locations:
city: Torrance
country: United States
facility: Los Angeles Biomedical Research Institute
state: California
city: Washington
country: United States
facility: The George Washington University
state: District of Columbia
city: Scarborough
country: United States
facility: Maine Center for Cancer Medicine and Blood Disorders
state: Maine
city: Bethesda
country: United States
facility: Suburban Hospital Cancer Program
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Hutzel Women's Health Specialists
state: Michigan
city: Newark
country: United States
facility: University of Medicine and Dentistry of New Jersey
state: New Jersey
city: Oklahoma City
country: United States
facility: University of Oklahoma
state: Oklahoma
city: Pawtucket
country: United States
facility: The Memorial Hospital of Rhode Island
state: Rhode Island
city: Burlington
country: United States
facility: Fletcher Allen Health Care
state: Vermont
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Madison
country: United States
facility: Univ. of Wisconsin Center for Women's Health and
state: Wisconsin
city: Kelowna
country: Canada
facility: BCCA - Cancer Centre for the Southern Interior
state: British Columbia
city: Vancouver
country: Canada
facility: BCCA - Vancouver Cancer Centre
state: British Columbia
city: London
country: Canada
facility: London Regional Cancer Program
state: Ontario
city: Sudbury
country: Canada
facility: Northeast Cancer Center Health Sciences
state: Ontario
city: Toronto
country: Canada
facility: Univ. Health Network-Princess Margaret Hospital
state: Ontario
Study officials:
affiliation: Massachusetts General Hospital
name: Paul E. Goss, MD, PhD
role: STUDY_CHAIR
References: