Clinical Trial: Letrozole in Preventing Breast Cancer in Healthy Postmenopausal Women at High Risk for Breast Cancer

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Phase I Dose-Finding Trial of Letrozole in Postmenopausal Women at High Risk for Breast Cancer

Brief Summary: This randomized phase I trial studies the side effects and the best dose of letrozole in preventing breast cancer in healthy postmenopausal women at high risk for breast cancer. Chemoprevention is the use of drugs to keep breast cancer from forming or coming back. The use of letrozole may keep cancer from forming in healthy postmenopausal women at high risk for breast cancer.

Detailed Summary:

PRIMARY OBJECTIVES:

I. Compare the effect of lower and intermittent doses of letrozole to standard letrozole therapy on estrogen suppression in postmenopausal women at high risk for developing breast cancer.

SECONDARY OBJECTIVES:

I. Comparison of the effect of lower and intermittent doses of letrozole to standard therapy on signs and symptoms of estrogen deficiency, including menopausal symptoms, serum lipid profile, and serum marker of bone turnover.

II. Comparison of the effect of lower and intermittent doses of letrozole to standard therapy on nuclear chromatin abnormality of breast epithelial cells collected by random periareolar fine needle aspiration (RPFNA).

TERTIARY OBJECTIVES:

I. Determine the prevalence of breast cancer stem cells in the fine needle breast aspirates and explore the potential intervention effect on the prevalence of breast cancer stem cells.

OUTLINE: Patients are randomized to 1 of 4 treatment arms.

ARM I: Patients receive 2.5 mg of letrozole orally (PO) thrice weekly for 6 months.

ARM II: Patients receive 1.0 mg of letrozole PO thrice weekly for 6 months.

ARM III: Patients receive 0.25 mg of letrozole PO thrice weekly for 6 months.

ARM IV: Patients receive 2.5 mg of letrozole PO once daily for 6 months.

After completion of study treatment, patients are followed up at week 30.


Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Percentage of serum estradiol suppression in postmenopausal women at high risk for breast cancer [ Time Frame: Baseline to week 30 ]

Three one-sided two-sample t-tests will be conducted on the ratios of the mean percentage of suppression simultaneously to test for non-inferiority. A multivariate t-distribution is used to derive the critical value and the power.


Original Primary Outcome: Percentage of serum estradiol suppression

Current Secondary Outcome:

  • Change in serum estrone levels [ Time Frame: Baseline to week 30 ]
    Three one-sided two-sample t-tests will be performed to evaluate the ratio of the mean changes (or percentage of changes) of each of the three intermittent dosing groups to that of the standard therapy control group simultaneously for each of the endpoints at an overall significance level of 5%.
  • Change in serum testosterone levels [ Time Frame: Baseline to week 30 ]
    Three one-sided two-sample t-tests will be performed to evaluate the ratio of the mean changes (or percentage of changes) of each of the three intermittent dosing groups to that of the standard therapy control group simultaneously for each of the endpoints at an overall significance level of 5%.
  • Menopausal symptoms as assessed by quality of life measures, as assessed by Medical Outcomes Study 36-item Short Form Health Survey (SF-36) and Menopause Specific Quality of Life Questionnaire (MENQOL) [ Time Frame: Up to week 30 ]
  • Nuclear chromatin abnormality as assessed by karyometry [ Time Frame: Up to week 30 ]


Original Secondary Outcome:

  • Effects of letrozole on serum estrone and testosterone levels
  • Menopausal symptoms as assessed by quality-of-life measures, lipid profile, and bone turnover
  • Nuclear chromatin abnormality


Information By: National Cancer Institute (NCI)

Dates:
Date Received: February 26, 2010
Date Started: March 2010
Date Completion:
Last Updated: October 17, 2014
Last Verified: October 2014