Trial Information

Evaluation of Diindolylmethane Supplementation to Modulate Tamoxifen Efficacy in Breast Cancer The Diindolylmethane Efficacy Study

PRIMARY OBJECTIVES:

I. Assess change in breast density using mammogram-based breast density measures as well as
a novel, quantitative fat-water ratio breast magnetic resonance imaging (FWR-MRI).

II. Evaluate the effect of an escalating daily dose of DIM on serum steroid hormones
(estrogen, sex hormone binding globulin [SHBG]) and urinary 2-hydroxyestrone:16
alpha-hydroxyestrone (2OHE1:16 alpha OHE1) ratio as well as serum tamoxifen (TAM)
metabolites (endoxifen). The study will be initiated at a dose of 75 mg twice daily (BID)
(total daily dose of 150 mg) for the first 10 study participants and then the dose will be
escalated to 150 mg DIM BID (total daily dose of 300 mg) if no treatment-related serious
adverse events (SAEs) are reported in the initial 10 subjects thru 3 months of treatment.

III. Expand on currently available toxicity and safety of DIM-TAM combination by assessing
reports of treatment associated side effects/adverse events including TAM-associated
endometrial toxicity (self-reported vaginal bleeding patterns and physician ordered vaginal
ultrasound), chemistry profiles, Functional Assessment of Cancer Therapy-Endocrine Subscale
(FACT-ES) scores and standard Common Terminology Criteria for Adverse Events (CTCAE)
tracking.

SECONDARY OBJECTIVES:

I. Collect fine-needle aspiration breast tissue samples (in a subset) and blood samples (all
participants) in order to explore change in mammary gland tissue architecture and
cellularity; and tissue markers and their association with change in breast density and to
explore changes in biomarkers of disease risk (e.g. cyclooxygenase-2 [COX-2],
deoxyribonucleic acid [DNA] adducts, oxidative stress, inflammation, etc) over time (pre and
post treatment) in both study arms.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive diindolylmethane orally (PO) BID for approximately 36 months.

ARM II: Patients receive placebo PO BID for approximately 36 months.

In both arms, treatment continues in the absence of unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.