Letrozole in Preventing Breast Cancer in Postmenopausal Women Who Are at Increased Risk for Breast Cancer Due to High Breast Density

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00238316
First received: October 12, 2005
Last updated: May 30, 2013
Last verified: September 2011
  Purpose

RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. The use of letrozole may stop cancer from forming or coming back in postmenopausal women who are at increased risk for breast cancer due to high breast density.

PURPOSE: This randomized phase II trial is studying how well letrozole works in preventing breast cancer in postmenopausal women who are at increased risk for breast cancer due to high breast density.


Condition Intervention Phase
Breast Cancer
Drug: letrozole
Other: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: A Randomized Feasibility Study of Letrozole in Postmenopausal Women at Increased Risk for Development of Breast Cancer as Evidenced by High Breast Density

Resource links provided by NLM:


Further study details as provided by NCIC Clinical Trials Group:

Primary Outcome Measures:
  • Percentage change of the BMD parameters from baseline BMD values [ Time Frame: 7 years ] [ Designated as safety issue: No ]
  • Percentage change of bone biomarker measurements (serum bone alkaline phosphatase and urine N-telopeptide) from baseline values [ Time Frame: 7 years ] [ Designated as safety issue: No ]

Enrollment: 68
Study Start Date: December 2000
Study Completion Date: February 2009
Primary Completion Date: April 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Letrozole Drug: letrozole
2.5 mg PO daily for 1 year
Placebo Comparator: Placebo Other: Placebo
2.5 mg PO daily for one 1 year

Detailed Description:

OBJECTIVES:

Primary

  • Determine the proportion of postmenopausal women who are at increased risk for the development or recurrence of breast cancer, based on high breast density (≥ grade 4), who achieve a decrease in breast density of ≥ 1 grade after treatment with letrozole for 1 year.

Secondary

  • Determine whether a decrease in breast density grade is sustained at 1 year in patients treated with this drug.
  • Correlate plasma estrogen profile (E1, E1S, E2) with breast density grade at baseline in these patients.
  • Determine the percentage of patients with breast tissue hyperplasia and atypical hyperplasia, as assessed by histopathological examination of breast tissue biopsies, before and after treatment with this drug.
  • Determine the changes in estrogen profile from baseline, at 1 year, and 1 year after cessation of this drug in these patients.
  • Compare changes in predetermined specific parameters of safety at the end of 1 year of treatment with this drug with baseline evaluations of these patients.
  • Determine whether modifications of these predetermined specific parameters of safety are sustained 1 year after cessation of treatment with this drug in these patients.
  • Determine the general safety of 1 year of treatment with this drug in these patients.
  • Compare the effects of this drug on menopause-specific quality of life of these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to breast density grade (4/6 vs 5/6 vs 6/6). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive oral letrozole once daily for 1 year in the absence of unacceptable toxicity.
  • Arm II: Patients receive oral placebo once daily for 1 year in the absence of unacceptable toxicity.

Menopause-specific quality of life is assessed at baseline and then at 12 and 24 months.

After completion of study treatment, patients are followed at 6 months and 1 year.

PROJECTED ACCRUAL: A total of 120 patients (80 in arm I and 40 in arm II) will be accrued for this study within 12 months.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • At increased risk for the development or recurrence of breast cancer, as defined by 1 of the following:

    • Baseline mammogram indicating mammographic density occupying ≥ 25% (grade 4/6, 5/6, or 6/6) of the breast tissue

      • No suspicion of breast cancer, unless subsequently ruled out
    • Prior ductal carcinoma in situ (DCIS)

      • Untreated disease OR > 6 months since completion of adjuvant endocrine therapy
      • Receptor status of lesion is not required
    • Prior invasive breast cancer

      • Breast cancer must have been surgically removed at time of original diagnosis with no evidence of metastases
  • No clinical evidence of breast cancer
  • Acceptable quality dual-energy x-ray absorptiometry (DEXA) of the L2-L4 postero-anterior (PA) spine and hip performed within past 6 months

    • Bone mass density T-score of either PA spine or hip must be ≥ 2.0 SD below the mean peak bone mass in young normal woman
  • Stable chronic leukemia allowed
  • Hormone receptor status:

    • Hormone receptor-negative, -positive, or -equivocal tumor

PATIENT CHARACTERISTICS:

Age

  • Postmenopausal

Sex

  • Female

Menopausal status

  • Postmenopausal, as defined by 1 of the following:

    • Over 55 years of age with spontaneous cessation of menses for ≥ 1 year
    • 55 years of age and under with spontaneous cessation of menses for ≤ 1 year, but amenorrheic (e.g., spontaneous or secondary to hysterectomy) AND follicle-stimulating hormone level > 34.4 IU/L
    • Bilateral oophorectomy

Performance status

  • Not specified

Life expectancy

  • Not specified

Hematopoietic

  • Not specified

Hepatic

  • Not specified

Renal

  • Not specified

Cardiovascular

  • No recent unstable myocardial infarction
  • No prior stroke
  • No high blood pressure
  • No other uncontrolled cardiovascular disease

Other

  • Other prior malignancies without metastatic disease allowed
  • Willing and able to complete quality of life questionnaires in either English or French
  • No uncontrolled metabolic or endocrine disease
  • No malabsorption syndrome

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No concurrent immunotherapy

Chemotherapy

  • No concurrent chemotherapy

Endocrine therapy

  • See Disease Characteristics
  • At least 3 months since prior and no concurrent hormone replacement therapy or raloxifene
  • At least 6 months since prior tamoxifen
  • No concurrent steroid therapy
  • No concurrent selective estrogen-receptor modulators
  • No other concurrent endocrine or hormonal therapy

Radiotherapy

  • Not specified

Surgery

  • See Disease Characteristics
  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: NCT00238316

Locations
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115-6084
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States, 02114
Canada, Alberta
Tom Baker Cancer Centre - Calgary
Calgary, Alberta, Canada, T2N 4N2
Canada, Nova Scotia
Nova Scotia Cancer Centre
Halifax, Nova Scotia, Canada, B3H 1V7
Canada, Ontario
Hamilton Osteoporosis Diagnostic Services
Hamilton, Ontario, Canada, L8N 1Y2
Ottawa Hospital Regional Cancer Centre - General Campus
Ottawa, Ontario, Canada, K1H 8L6
St. Catharines General Hospital at Niagara Health System
St. Catharines, Ontario, Canada, L2R 5K3
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Toronto Sunnybrook Regional Cancer Centre at Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada, M4N 3M5
Canada, Quebec
Hotel Dieu de Montreal
Montreal, Quebec, Canada, H2W 1T8
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: NCT00238316     History of Changes
Other Study ID Numbers: MAP1, CAN-NCIC-MAP1, CDR0000445442
Study First Received: October 12, 2005
Last Updated: May 30, 2013
Health Authority: United States: Federal Government

Keywords provided by NCIC Clinical Trials Group:
breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Letrozole
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 20, 2014