Bexarotene in Preventing Breast Cancer in Women at Genetic Risk

Study Overview
=================
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.

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

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Drug: bexarotene


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bexarotene<br>Bexarotene / Targretin | Drug: bexarotene<br>* This drug is a retinoid. The anti-tumor action of retinoids, as well as their potential in chemoprevention, supports the need to further identify the spectrum of responsive tumors, to identify the molecular mechanisms associated with retinoid action, and to identify and develop new retinoids that have unique properties and an improved therapeutic index.<br>* Other names: Targretin;|
| Placebo Comparator: Sugar Pill<br>Sugar pill / placebo | Drug: bexarotene<br>* This drug is a retinoid. The anti-tumor action of retinoids, as well as their potential in chemoprevention, supports the need to further identify the spectrum of responsive tumors, to identify the molecular mechanisms associated with retinoid action, and to identify and develop new retinoids that have unique properties and an improved therapeutic index.<br>* Other names: Targretin;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Apoptosis at day 29 during study treatment |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
breast cancer