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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00688246
• Other study ID #: MAP3B
• Secondary ID: CAN-NCIC-MAP3BPF
• Status: Completed
• Start date: July 10, 2008
• Est. completion date: January 10, 2013

Study information

• Verified date: March 2020
• Source: Canadian Cancer Trials Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 238
• Est. completion date: January 10, 2013
• Est. primary completion date: October 31, 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 35 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Osteoporosis

Intervention

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.

Locations

Country	Name	City	State
Canada	BCCA - Cancer Centre for the Southern Interior	Kelowna	British Columbia
Canada	London Regional Cancer Program	London	Ontario
Canada	Northeast Cancer Center Health Sciences	Sudbury	Ontario
Canada	Univ. Health Network-Princess Margaret Hospital	Toronto	Ontario
Canada	BCCA - Vancouver Cancer Centre	Vancouver	British Columbia
United States	Suburban Hospital Cancer Program	Bethesda	Maryland
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Fletcher Allen Health Care	Burlington	Vermont
United States	Hutzel Women's Health Specialists	Detroit	Michigan
United States	Univ. of Wisconsin Center for Women's Health and	Madison	Wisconsin
United States	University of Medicine and Dentistry of New Jersey	Newark	New Jersey
United States	University of Oklahoma	Oklahoma City	Oklahoma
United States	The Memorial Hospital of Rhode Island	Pawtucket	Rhode Island
United States	Maine Center for Cancer Medicine and Blood Disorders	Scarborough	Maine
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Los Angeles Biomedical Research Institute	Torrance	California
United States	The George Washington University	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
NCIC Clinical Trials Group

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		2 years
Secondary	Change in BMD as measured by DEXA scans of the spine (L1-L4) and total hip 5 years after randomization on CAN-NCIC-MAP3		5 years
Secondary	Changes in markers of bone formation and resorption 1 and 5 years after randomization on CAN-NCIC-MAP3		5 years
Secondary	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		2 years
Secondary	Number of clinical skeletal fractures by radiology report		2 years