Letrozole in Preventing Breast Cancer in Postmenopausal Women

NCT ID: NCT00090857

Last Updated: 2018-03-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-02-28
• Study Completion Date: 2013-03-31

Brief Summary

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.

Detailed Description

OBJECTIVES:

Primary

• The primary outcome of the study is the change in bone mineral density following a year on letrozole vs. a year on placebo.

Secondary

• 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 through evaluation of menopausal symptoms (including hot flushes, weight changes, sexual functioning, and genitourinary effects), blood lipid levels, markers of bone turnover, and multidimensional quality of life.
• Determine the effect of letrozole-induced reduction of plasma estradiol levels on mammographic percent breast density.
• Obtain background information for a future large chemoprevention trial to address the question of whether a reduction in plasma estradiol levels can reduce the risk of breast cancer in postmenopausal women.

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

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

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Letrozole

Participants in this arm received 2.5 mg of letrozole per day for a duration of 12 months; followed by an optional 4 years. Treatment continued in the absence of unacceptable toxicity or diagnosis of invasive breast cancer, ductal carcinoma in situ, or any non-breast primary cancer.

Group Type: EXPERIMENTAL

Letrozole

Intervention Type: DRUG

Placebo

Participants in this arm received 1 tablet per day which contained the inert ingredients from the letrozole tablet, for a duration of 12 months; followed by an optional 5 years of letrozole.Treatment continued in the absence of unacceptable toxicity or diagnosis of invasive breast cancer, ductal carcinoma in situ, or any non-breast primary cancer.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Interventions

Letrozole

Intervention Type: DRUG

Placebo

Intervention Type: OTHER

Other Intervention Names

Femara

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Jonsson Comprehensive Cancer Center

OTHER

Sponsor Role: collaborator

Dana-Farber Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Judy E. Garber, MD

Garber, Judith MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Judy Garber, MD

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Patricia A. Ganz, MD

Role: PRINCIPAL_INVESTIGATOR

Jonsson Comprehensive Cancer Center

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Dan L. Duncan Cancer Center at Baylor College of Medicine

Houston, Texas, United States

Countries

United States

Other Identifiers

P50CA089393

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA006516

Identifier Type: NIH

Identifier Source: secondary_id

View Link

DFCI-00024

Identifier Type: -

Identifier Source: secondary_id

UCLA-0210012-02

Identifier Type: -

Identifier Source: secondary_id

DFCI-00024

Identifier Type: -

Identifier Source: org_study_id

NCT00165529

Identifier Type: -

Identifier Source: nct_alias

NCT00577551

Identifier Type: -

Identifier Source: nct_alias