Clinical trial NCT00354302: Bone Mineral Density in Postmenopausal Women With Primary Breast Cancer Who Are Receiving Treatment on Clinical Trial
Official title: The Influence of Five Years of Adjuvant Anastrozole or Exemestane on Bone Mineral Density In Postmenopausal Women With Primary Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Osteoporosis
Keywords: osteoporosis
stage I breast cancer
stage II breast cancer
stage IIIA breast cancer
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: North Central Cancer Treatment Group
name: SWOG Cancer Research Network
First posted: 2006-07-20
Enrollment: 497
Sex: FEMALE
Minimum age (years): 45
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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

PURPOSE: This phase III trial is studying bone mineral density in postmenopausal women with primary breast cancer who are receiving treatment on clinical trial CAN-NCIC-MA27.

Detailed description: OBJECTIVES:

* Determine whether there is a clinically relevant difference in bone mineral density (BMD) at 2 years in postmenopausal women with primary breast cancer (with or without osteopenia or osteoporosis) treated with exemestane vs anastrozole on protocol CAN-NCIC-MA27.

OUTLINE: This is a multicenter, companion study. Patients are stratified according to baseline bone mineral density (BMD) measurement (T-score\* ≥ -2.0 standard deviation \[SD\] \[no osteopenia or osteoporosis\] vs T-score\* \< -2.0 SD).

NOTE: \*The lowest of the two T-scores: L1-L4 or total hip

Blood samples for the identification of bone biomarkers (formation marker: serum amino-terminal procollagen 1 extension peptide \[P1NP\] and resorption marker: serum N-telopeptide) are obtained at baseline and at 6 and 12 months. BMD is determined by dual-energy x-ray absorptiometry (DEXA) at baseline and then annually for 5 years (or for as long as patient is receiving treatment on protocol CAN-NCIC-MA27).

Patients receive oral calcium and oral cholecalciferol (vitamin D) daily. Patients with osteopenia or osteoporosis (stratum II) also receive oral bisphosphonate therapy

PROJECTED ACCRUAL: A total of 408 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Enrolled in and meets eligibility requirements for protocol CAN-NCIC-MA27
* Acceptable quality dual-energy x-ray absorptiometry (DEXA) of the L1-L4 postero-anterior spine and hip within 12 weeks prior to randomization on protocol CAN-NCIC-MA27
* Hormone receptor status:

  * Estrogen receptor- and/or progesterone receptor-positive tumor

PATIENT CHARACTERISTICS:

* Female
* Postmenopausal
* No malabsorption syndrome
* No known cholecalciferol (vitamin D) deficiency, active hyper- or hypoparathyroidism, or Paget's disease
* No uncontrolled thyroid disease, Cushing's disease, or other pituitary disease
* No other bone disease (including osteomalacia or osteogenesis imperfecta)

PRIOR CONCURRENT THERAPY:

* More than 6 months since prior drugs (investigational or not), including bisphosphonates, for the prevention of osteoporosis (stratum I)
* More than 12 months since prior and no concurrent anticonvulsants
* More than 6 months since prior and no concurrent corticosteroids at doses \> 5 mg/day of prednisone (or equivalent) for \> 2 weeks
* More than 12 months since prior and no concurrent anabolic steroids
* No prior bisphosphonates (stratum II)
* No concurrent sodium fluoride at daily doses ≥ 5 mg/day
* No long-term (i.e., \> 6 months) use of coumarins
* No concurrent drugs (investigational or not), including bisphosphonates, for the prevention of osteoporosis (for patients with no osteopenia or osteoporosis \[stratum I\])

Primary outcomes:
measure: Percentage change of bone mineral density (BMD) measured at 2 years (from baseline) in the L1-L4 region of the spine and the hip
timeFrame: 5 years
Secondary outcomes:
measure: Percentage change in BMD at 5 years (from baseline)
timeFrame: 5 years
measure: Mean percentage change in BMD at 1, 3, and 5 years (from baseline)
timeFrame: 5 years
measure: Proportion of patients without osteopenia or osteoporosis (stratum I) who develop BMD below the absolute threshold for osteopenia (< -2.0 standard deviation below the mean), suffer any osteoporotic fracture, or have an asymptomatic fracture revealed ...
timeFrame: 5 years
measure: Percentage of patients with osteopenia or osteoporosis (stratum II) who have ≥ 5% improvement of BMD at 2 years post randomization on protocol CAN-NCIC-MA27 and who have clinically apparent osteoporosis-related fracture of the long bones
timeFrame: 5 years
measure: Pattern of change in bone biomarkers from baseline
timeFrame: 5 years
measure: Clinical safety and tolerability of study medications
timeFrame: 5 years
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: BCCA - Vancouver Cancer Centre
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Moncton
country: Canada
facility: The Moncton Hospital
state: New Brunswick
city: Saint John
country: Canada
facility: Atlantic Health Sciences Corporation
state: New Brunswick
city: Cambridge
country: Canada
facility: Cambridge Memorial Hospital
state: Ontario
city: Sault Ste. Marie
country: Canada
facility: Algoma District Cancer Program
state: Ontario
city: Thunder Bay
country: Canada
facility: Thunder Bay Regional Health Science Centre
state: Ontario
city: Toronto
country: Canada
facility: Odette Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: Univ. Health Network-Princess Margaret Hospital
state: Ontario
city: Greenfield Park
country: Canada
facility: Hopital Charles LeMoyne
state: Quebec
city: Quebec City
country: Canada
facility: CHA-Hopital Du St-Sacrement
state: Quebec
city: Regina
country: Canada
facility: Allan Blair Cancer Centre
state: Saskatchewan
Study officials:
affiliation: Massachusetts General Hospital
name: Paul E. Goss, MD, PhD
role: STUDY_CHAIR
affiliation: Mayo Clinic
name: James N. Ingle, MD
role: STUDY_CHAIR
affiliation: Herbert Irving Comprehensive Cancer Center
name: Dawn Hershman, MD
role: STUDY_CHAIR
References:
citation: Goss PE, Hershman DL, Cheung AM, Ingle JN, Khosla S, Stearns V, Chalchal H, Rowland K, Muss HB, Linden HM, Scher J, Pritchard KI, Elliott CR, Badovinac-Crnjevic T, St Louis J, Chapman JA, Shepherd LE. Effects of adjuvant exemestane versus anastrozole on bone mineral density for women with early breast cancer (MA.27B): a companion analysis of a randomised controlled trial. Lancet Oncol. 2014 Apr;15(4):474-82. doi: 10.1016/S1470-2045(14)70035-X. Epub 2014 Mar 11.