Clinical trial NCT00055991: Bexarotene in Preventing Breast Cancer in Women at Genetic Risk
Official title: A Multicenter Randomized Double-Blind Trial Of Targretin Capsules Modifying Immunophenotypic Markers Related To Breast Cancer Progression In Breast Tissue From Genetically Identified High Risk Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breast Cancer
Keywords: breast cancer
Lead sponsor: Baylor Breast Care Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-03-07
Enrollment: 87
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

Detailed 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.

Eligibility 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

Primary outcomes:
measure: Chemopreventive effect as determine by a modification of the immunophenotypic characteristics of normal breast tissue at day 29 during study treatment and day 30 after study completion
Secondary outcomes:
measure: Apoptosis at day 29 during study treatment
Other outcomes:
Locations:
city: Washington
country: United States
facility: Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
state: District of Columbia
city: Houston
country: United States
facility: M.D. Anderson Cancer Center at University of Texas
state: Texas
city: Houston
country: United States
facility: Dan L. Duncan Cancer Center at Baylor College of Medicine
state: Texas
city: San Antonio
country: United States
facility: Cancer Therapy and Research Center
state: Texas
Study officials:
affiliation: Baylor College of Medicine
name: Richard M. Elledge, MD
role: STUDY_CHAIR
References: