Letrozole in Treating Healthy Postmenopausal Women at High Risk for Breast Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01077453
First received: February 26, 2010
Last updated: August 11, 2014
Last verified: June 2014
  Purpose

This randomized phase I trial studies the side effects and the best dose of letrozole in treating healthy postmenopausal women at high risk for breast cancer. Letrozole may prevent breast cancer in postmenopausal women at high risk for breast cancer. It is not yet known which dose of letrozole is more effective in these women.


Condition Intervention Phase
Lobular Breast Carcinoma in Situ
Drug: letrozole
Other: quality-of-life assessment
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Phase I Dose-Finding Trial of Letrozole in Postmenopausal Women at High Risk for Breast Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Percentage of serum estradiol suppression in postmenopausal women at high risk for breast cancer [ Time Frame: Up to week 30 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Changes in serum estrone and testosterone levels [ Time Frame: Baseline to week 30 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Nuclear chromatin abnormality as assessed by karyometry [ Time Frame: Up to week 30 ] [ Designated as safety issue: No ]

Enrollment: 112
Study Start Date: March 2010
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (2.5 mg letrozole)
Patients receive 2.5 mg of letrozole PO thrice weekly for 6 months.
Drug: letrozole
Given orally
Other Names:
  • CGS 20267
  • Femara
  • LTZ
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm II (1.0 mg letrozole)
Patients receive 1.0 mg of letrozole PO thrice weekly for 6 months.
Drug: letrozole
Given orally
Other Names:
  • CGS 20267
  • Femara
  • LTZ
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm III (0.25 mg letrozole)
Patients receive 0.25 mg of letrozole PO thrice weekly for 6 months.
Drug: letrozole
Given orally
Other Names:
  • CGS 20267
  • Femara
  • LTZ
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm IV (2.5 mg letrozole)
Patients receive 2.5 mg of letrozole PO once daily for 6 months.
Drug: letrozole
Given orally
Other Names:
  • CGS 20267
  • Femara
  • LTZ
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   35 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy postmenopausal women at "high risk" for breast cancer will be eligible for the study; definition of menopause will be:

    • Amenorrhea for at least 12 months, or
    • History of hysterectomy and bilateral salpingo-oophorectomy, or
    • At least 55 years of age with prior hysterectomy with or without oophorectomy, or
    • Age 35 to 54 with a prior hysterectomy without oophorectomy OR with a status of ovaries unknown with documented follicle-stimulating hormone level demonstrating elevation in postmenopausal range
    • "High risk" for breast cancer will be defined as:

      • Prior histologically confirmed lobular carcinoma in situ (LCIS) treated by local excision only, or
      • At least 1.66% probability of invasive breast cancer within 5 years using the Breast Cancer Risk Assessment Tool
  • ECOG performance status 0 or 1; Karnofsky 80% or above
  • Leukocytes >= 3,000/uL
  • Absolute neutrophil count >= 1,500/uL
  • Platelets >= 100,000/uL
  • Total bilirubin =< 2.0 mg/dL
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.0 X institutional ULN
  • Creatinine =< 1 X institutional ULN
  • Recent mammogram negative for breast cancer, Breast Imaging-Reporting and Data System (BIRADS) score < 3 (within the last 12 months)
  • Ability to understand and the willingness to sign a written informed consent document; only potential participants with the ability to understand and the willingness to sign a written document will be presented with an informed consenting document

Exclusion Criteria:

  • Women diagnosed with osteoporosis (previously or on screening dual-energy X-ray absorptiometry [DEXA] for this study) and not on a stable dose of long or short-acting bisphosphonates therapy for at least 3 months will be excluded from the study; women diagnosed with osteoporosis and on raloxifene (Evista) therapy will be excluded from the study; use of calcium and/or vitamin D for osteoporosis prevention or treatment is allowed; women with osteopenia will be allowed to participate in this study
  • Have had invasive cancer within the past five years except non-melanoma skin cancer
  • Evidence of suspicious of malignant disease on bilateral mammogram within the past year unless ruled out by further evaluation
  • History of prior invasive breast cancer or intraductal carcinoma in situ, or history of prior radiation therapy to the chest or breast
  • Participants may not be receiving any other investigational agents; participants may not be concurrently enrolled in another breast cancer prevention intervention trial
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to letrozole
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Within 3 months since prior estrogen or progesterone replacement therapy, oral contraceptives, androgens, luteinizing hormone-releasing hormone analogs, prolactin inhibitors, or antiandrogens
  • Within 3 months since prior tamoxifen, raloxifene, or other selective estrogen-receptor modulators
  • Within 3 months since regular use (more than 2 times a week) of prior estrogenic supplements or herbal remedies
  • History of bleeding or clotting disorder; current or recent (within 3 months) use of Coumadin, Plavix or other systemic anticoagulant other than aspirin is not permitted if subject chooses to participate in the optional RPFNA procedure; if a subject chooses not to participate in the RPFNA procedure, prior or current treatment with systemic anticoagulants is permitted
  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: NCT01077453

Locations
United States, Arizona
Arizona Cancer Center - Tucson
Tucson, Arizona, United States, 85724-5024
University of Arizona Health Sciences Center
Tucson, Arizona, United States, 85724
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Investigators
Principal Investigator: Ana Lopez University of Arizona Health Sciences Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01077453     History of Changes
Other Study ID Numbers: NCI-2013-00757, NCI-2013-00757, 09-0869-04, UAZ08-12-02, N01CN35158, P30CA023074
Study First Received: February 26, 2010
Last Updated: August 11, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Carcinoma in Situ
Carcinoma, Lobular
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adenocarcinoma
Neoplasms, Ductal, Lobular, and Medullary
Letrozole
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 16, 2014