Letrozole in Preventing Breast Cancer in Postmenopausal Women

This study has been completed.
Sponsor:
Collaborators:
Jonsson Comprehensive Cancer Center
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00090857
First received: September 7, 2004
Last updated: April 10, 2009
Last verified: October 2007
  Purpose

RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. Letrozole may be effective in preventing the development or recurrence of breast cancer in postmenopausal women who are at increased risk of developing breast cancer because of elevated estradiol levels.

PURPOSE: This randomized phase II trial is studying how well letrozole works in preventing breast cancer in postmenopausal women with elevated estradiol levels.


Condition Intervention Phase
Breast Cancer
Drug: letrozole
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Double-Blind
Primary Purpose: Prevention
Official Title: A Pilot Study of Aromatase Inhibitors for Women at Increased Risk of Breast Cancer Based on Estradiol Levels

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Safety, acceptability, and adherence [ Designated as safety issue: Yes ]
  • Effects on menopausal symptoms [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Effects on mammographic percent breast density [ Designated as safety issue: No ]

Estimated Enrollment: 110
Study Start Date: September 2000
Detailed Description:

OBJECTIVES:

Primary

  • Compare the safety, acceptability, and adherence to letrozole vs placebo in postmenopausal women at increased risk for the development or recurrence of breast cancer based on elevated plasma estradiol levels.
  • Compare the effects of these regimens on menopausal symptoms (including hot flushes, weight changes, sexual functioning, and genitourinary effects), blood lipid levels, markers of bone turnover, and multidimensional quality of life in patients treated with these regimens.

Secondary

  • Determine the effect of letrozole-induced reduction of plasma estradiol levels on mammographic percent breast density in these patients.

OUTLINE: This is a pilot, randomized, double-blind, placebo-controlled, multicenter study. Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive oral letrozole once daily for 1 year. Patients may then receive additional oral letrozole once daily for up to 4 years.
  • Arm II: Patients receive oral placebo once daily for 1 year. Patients may then receive oral letrozole once daily for up to 5 years.

In both arms, treatment continues in the absence of unacceptable toxicity or diagnosis of invasive breast cancer, ductal carcinoma in situ, or any non-breast primary cancer.

Quality of life is assessed at baseline and then at 3, 6, and 12 months.

PROJECTED ACCRUAL: A total of 110 patients (73 for arm I and 37 for arm II) will be accrued for this study.

  Eligibility

Ages Eligible for Study:   35 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • At increased risk for the development or recurrence of breast cancer, defined as an estradiol level ≥ 9 pg/mL
  • No evidence of suspicious or malignant disease, based on the following examinations:

    • Clinical bilateral breast examination within the past 6 months
    • Bilateral* mammogram within 3 months before randomization OR within 30 days after randomization
    • Pelvic exam normal within the past 5 years
    • General physical exam within the past 6 months NOTE: *Unilateral mammogram of the uninvolved breast for patients with prior invasive breast cancer or ductal carcinoma in situ (DCIS)
  • Bone density scan within 2 standard deviations from normal within the past 30 days

    • Bone density scan ≥ 2 standard deviations below normal allowed if approved by the study physician
  • At least 1 breast that has not been previously treated with radiotherapy or surgery (for patients with prior invasive breast cancer or DCIS)
  • Hormone receptor status:

    • Not specified

PATIENT CHARACTERISTICS:

Age

  • 35 and over

Sex

  • Female

Menopausal status

  • Postmenopausal, defined by any of the following criteria:

    • At least 12 months without spontaneous menstrual bleeding
    • Prior hysterectomy and bilateral salpingo-oophorectomy
    • ≥ 55 years of age with a prior hysterectomy with or without oophorectomy
    • < 55 years of age with a prior hysterectomy without oophorectomy OR the status of the ovaries is unknown AND follicle-stimulating hormone (FSH) level is in the postmenopausal range

Performance status

  • Normal activity must not be restricted for a significant portion of the day

Life expectancy

  • At least 10 years

Hematopoietic

  • Complete blood count with differential normal

    • Prior benign neutropenia allowed provided the granulocyte count is ≥ 1,500/mm^3

Hepatic

  • Bilirubin normal
  • Alkaline phosphatase normal
  • SGOT and SGPT normal

Renal

  • Creatinine normal

Cardiovascular

  • No uncontrolled cardiovascular disease

Other

  • Not pregnant
  • No other malignancy within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
  • No osteoporosis
  • No hyperlipidemia
  • No mental health status resulting in cognitive or emotional impairment that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • Not specified

Endocrine therapy

  • More than 30 days since prior AND no concurrent use of any of the following hormonal agents:

    • Estrogen or progesterone replacement therapy
    • Oral contraceptives
    • Raloxifene or other plasma estrogen receptor modulators (SERMs)
    • Androgens (e.g., danazol)
    • Luteinizing hormone-releasing hormone (LHRH) analogs (e.g., goserelin or leuprolide)
    • Prolactin inhibitors (e.g., bromocriptine)
    • Antiandrogens (e.g., cyproterone)
  • More than 60 days since prior AND no concurrent tamoxifen
  • No prior aromatase inhibitors (for patients with prior invasive breast cancer or DCIS)
  • No concurrent phytoestrogenic dietary supplements (e.g., soy, ginseng, or other natural products)

    • Dietary soy allowed

Radiotherapy

  • See Disease Characteristics

Surgery

  • See Disease Characteristics
  • No prior bilateral mastectomy

Other

  • More than 60 days since prior treatment for invasive breast cancer or DCIS
  • More than 30 days since prior bisphosphonates or calcitonin
  • No prior or concurrent participation on a treatment study for invasive breast cancer or DCIS
  • No concurrent participation in any other cancer prevention study or osteoporosis prevention study involving pharmacologic agents
  • No concurrent calcitonin
  • No concurrent bisphosphonate therapy
  • Concurrent cholecalciferol (vitamin D) and calcium to augment bone mineral density allowed
  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: NCT00090857

Locations
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104-4283
United States, Texas
Dan L. Duncan Cancer Center at Baylor College of Medicine
Houston, Texas, United States, 77030
Sponsors and Collaborators
Dana-Farber Cancer Institute
Jonsson Comprehensive Cancer Center
Investigators
Principal Investigator: Judy Garber, MD Dana-Farber Cancer Institute
Principal Investigator: Patricia A. Ganz, MD Jonsson Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00090857     History of Changes
Obsolete Identifiers: NCT00165529, NCT00577551
Other Study ID Numbers: CDR0000375585, DFCI-00024, UCLA-0210012-02
Study First Received: September 7, 2004
Last Updated: April 10, 2009
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
breast cancer
stage I breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
stage IV breast cancer
breast cancer in situ
ductal breast carcinoma in situ

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 September 30, 2014