Bexarotene in Preventing Breast Cancer in Women at Genetic Risk

Baylor College of Medicine

Status and phase

Completed

Phase 1

Conditions

Breast Cancer

Treatments

Drug: bexarotene

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00055991

5U19CA086809 (U.S. NIH Grant/Contract)

CDR0000271913

Details and patient eligibility

About

RATIONALE: Chemoprevention therapy uses certain drugs to try to prevent the development or recurrence of cancer. It is not yet known whether bexarotene is effective in preventing breast cancer.

PURPOSE: Randomized clinical trial to study the effectiveness of bexarotene in preventing breast cancer in women who are at genetic risk of developing breast cancer.

Full description

OBJECTIVES:

Determine whether bexarotene can modify immunophenotypic markers related to breast cancer progression in women at high genetic risk for breast cancer.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to menopausal status (women with a uterus who have not had a menstrual period for more than 1 year vs any woman over 55 years old vs women 55 years and under without a uterus whose follicle-stimulating hormone is in the postmenopausal range). Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive oral bexarotene once daily on days 1-28.
Arm II: Patients receive oral placebo as in arm I. In both arms, treatment continues in the absence of unacceptable toxicity or elevation of triglycerides to greater than 800 mg/dL. Patients undergo 2 breast biopsies in the same location on days 1 and 29.

Patients are followed at 30 days.

PROJECTED ACCRUAL: A total of 100 patients (50 per treatment arm) will be accrued for this study within 4 years.

Enrollment

87 patients

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Known carrier of a BRCA-1 or BRCA-2 mutation
- Copy of laboratory report stating results must be available for review OR
At risk for carrying a BRCA-1 or BRCA-2 mutation
- At least 10% risk by Parmigiana probability model
Must have at least 1 breast that has never been involved with cancer and has not been irradiated
Hormone receptor status:
- Not specified

PATIENT CHARACTERISTICS:

Age

18 and over

Sex

Female

Menopausal status

Not specified

Performance status

Not specified

Life expectancy

Not specified

Hematopoietic

WBC greater than 4,000/mm^3
Platelet count greater than 100,000/mm^3
Hematocrit greater than 30%

Hepatic

Bilirubin no greater than 1.5 times upper limit of normal (ULN)
ALT no greater than 1.5 times ULN
Alkaline phosphatase no greater than 1.5 times ULN
Albumin no greater than 1.5 times ULN
No biliary tract disease

Renal

Creatinine no greater than 1.5 times ULN

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception for 1 month before, during, and for 1 month after study therapy
Triglycerides normal
Thyroid-stimulating hormone and thyroxine normal
Willing to undergo 2 duplicate needle biopsies of the breast
Willing to undergo genetic testing for BRCA-1 and BRCA-2
No uncontrolled hyperlipidemia
No nontoxic goiter or thyroid enlargement
No severe underlying chronic illness or disease
No uncontrolled diabetes
No history of pancreatitis
No cancer within the past year except skin cancer or carcinoma in situ of the cervix (defined from the date of first diagnosis)
No concurrent alcohol use (greater than 3 drinks or its equivalent per day)

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

More than 1 year since prior chemotherapy for a neoplasm

Endocrine therapy

More than 3 months since prior postmenopausal hormonal therapy (including estrogens or progestins)
More than 3 months since prior tamoxifen or other selective estrogen-receptor modulators
No concurrent hormone replacement therapy
Concurrent thyroid hormone supplementation allowed

Radiotherapy

See Disease Characteristics

Surgery

Not specified

Other

More than 30 days since prior investigational medications
More than 3 months since prior oral vitamin A supplements greater than the recommended daily requirement (5,000 IU) or therapeutic oral or topical vitamin A derivatives (e.g., isotretinoin)
No concurrent participation in a study of an investigational agent
No concurrent medications known to be associated with pancreatic toxicity or to increase triglyceride levels