Indole-3-Carbinol in Preventing Breast Cancer in Nonsmoking Women Who Are at High Risk For Breast Cancer

Multiple Daily Dose Phase I Safety And Pharmacokinetic Clinical Study Of Indole-3-Carbinol

RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. Indole-3-carbinol may be effective in preventing breast cancer.

PURPOSE: Phase I trial to study the effectiveness of indole-3-carbinol in preventing breast cancer in nonsmoking women who are at high risk for breast cancer.

OBJECTIVES:

• Determine the safety and tolerability of indole-3-carbinol for the prevention of breast cancer in non-smoking women at high risk for breast cancer.
• Determine the pharmacokinetics of this drug in these participants.
• Determine the effect of this drug on metabolites of estrogen in urine of these participants.
• Determine other additional effects of this drug on selected indicators of drug metabolism and reproductive and hormonal function in these participants.
• Assess any possible antineoplastic activity of this drug in these participants.
• Determine the quality of life of participants receiving this drug.

OUTLINE: This is a single-blind study.

Participants ingest study compound twice daily on weeks 1-12 or 1-16. Study compound is dispensed on weeks 1, 5, and 9. At times, study compound is oral placebo, and at other times, oral indole-3-carbinol.

Quality of life is assessed at baseline and then every 4 weeks during study therapy.

PROJECTED ACCRUAL: A total of 18 participants will be accrued for this study within 9 months.

DISEASE CHARACTERISTICS:

• Women at high risk for breast cancer, defined by at least 1 of the following criteria:

  • Projected 5-year probability of invasive breast cancer at least 1.66%, as determined by the Breast Cancer Risk Assessment Tool
  • Prior node-negative breast cancer
  • Prior biopsy indicating atypical lobular or ductal hyperplasia or carcinoma in situ
  • Age 60 and over

• Non-smoker confirmed by urine cotinine test

• No concurrent breast cancer

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age:

• 18 to 70

Sex:

• Female

Menopausal status:

• Premenopausal (regular menstrual cycles of 24-36 days within the past 6 months) OR
• Postmenopausal (no menstrual cycle for at least 6 months)

Performance status:

• Not specified

Life expectancy:

• At least 1 year

Hematopoietic:

• Absolute granulocyte count greater than 1,500/mm^3
• Hemoglobin greater than 10 g/dL

Hepatic:

• Bilirubin less than 1.8 mg/dL
• Aspartate aminotransferase (AST) and Alanine transaminase (ALT) less than 110 U/L
• Alkaline phosphatase less than 300 U/L
• Albumin greater than 3 g/dL

Renal:

• Creatinine less than 2.0 mg/dL

Cardiovascular:

• No acute or unstable cardiovascular condition based on electrocardiogram

Other:

• Mild seasonal allergies allowed
• No serious or life-threatening drug allergies
• No other serious intolerances or allergies
• No more than 20% above or below ideal body weight
• No acute or unstable medical condition by physical examination or laboratory tests
• No chronic headaches, dysphoria, fatigue, dizziness, blurred vision, insomnia, rhinorrhea, nausea, vomiting, abdominal pain, diarrhea, constipation, or similar conditions
• No serious illness requiring chronic drug therapy
• No active malignancy
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception 1 month before, during, and for 1 month after study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• At least 2 months since prior hormonal therapy as contraception or hormone replacement therapy (HRT)
• No concurrent sex hormones as contraception for premenopausal women
• No concurrent HRT for postmenopausal women

Radiotherapy:

• Not specified

Surgery:

• Not specified

Other:

• At least 6 months since prior investigational drugs
• At least 1 month since prior weekly consumption of more than 3 medium servings (half cup each) of cruciferous vegetables
• No concurrent vegetarian diet or weekly consumption of more than 3 medium servings (half cup each) of cruciferous vegetables
• No continuous supplement intake
• No recent change in medications or dosage of medications