Bexarotene in Preventing Breast Cancer in Women at Genetic Risk

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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: bexarotene

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.

• Study Type: Interventional
• Enrollment (Actual): 87
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
  • Texas
    • Houston, Texas, United States, 77030-4009
      • M.D. Anderson Cancer Center at University of Texas
    • Houston, Texas, United States, 77030
      • Dan L. Duncan Cancer Center at Baylor College of Medicine
    • San Antonio, Texas, United States, 78229
      • Cancer Therapy and Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bexarotene; Bexarotene / Targretin	Drug: bexarotene; 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.; Other Names: Targretin
Placebo Comparator: Sugar Pill; Sugar pill / placebo	Drug: bexarotene; 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.; Other Names: Targretin

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure
Apoptosis at day 29 during study treatment

Collaborators and Investigators

• Sponsor: Baylor Breast Care Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Richard M. Elledge, MD, Baylor College of Medicine

Study record dates

Study Major Dates

• Study Start: September 1, 2001
• Primary Completion (Actual): September 1, 2006
• Study Completion (Actual): September 1, 2006

Study Registration Dates

• First Submitted: March 6, 2003
• First Submitted That Met QC Criteria: March 6, 2003
• First Posted (Estimate): March 7, 2003

Study Record Updates

• Last Update Posted (Estimate): February 5, 2013
• Last Update Submitted That Met QC Criteria: February 4, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Keywords: breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Antineoplastic Agents; Bexarotene
• Other Study ID Numbers: CDR0000271913; 5U19CA086809 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No