Stage IA Breast Cancer, Stage IB Breast Cancer, Stage II Breast Cancer, Stage IIIA Breast Cancer
Conditions
Brief summary
This phase II/III trial studies how well diindolylmethane (DIM) works and compares it to placebo in treating patients with breast cancer. DIM may slow the growth of tumor cells and be an effective treatment for breast cancer.
Detailed description
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.
Interventions
DIETARY_SUPPLEMENTdiindolylmethane
Given PO
DIETARY_SUPPLEMENTplacebo
Given PO
Sponsors
National Cancer Institute (NCI)
University of Arizona
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Prescribed TAM as adjuvant therapy for early stage (0, I, II, IIIa) breast cancer or as chemoprevention in women at high risk for breast cancer * New or planned prescription of TAM therapy; ineligible for randomization until on TAM for \> 3 months with the expectation to continue use for \> 18 months * Mammogram with Breast Imaging Reporting and Data System (BIRADS) score of \>= 2; (equivalent to the following and similar breast density descriptive terms found in mammogram reports: 2 = scattered fibroglandular elements/densities; 3 = heterogeneously dense tissue; 4 = extremely dense tissue) * No use of soy-based dietary supplements or willingness to discontinue use, complete a 4-week wash-out period, prior to randomization, and refrain from use during trial period * If pre-menopausal, non-pregnant (confirmed with urinary pregnancy test); practicing birth control or s/p oophorectomy * Able to complete study run-in activities, including taking study-provided placebo pill twice daily (AM & PM) and recording pill intake and any symptoms experienced on a study calendar, with a compliance rate of at least 80% * Normal blood chemistry test that includes sodium and specific kidney and liver function tests (creatinine, alanine amino transferase-ALT, aspartate amino transferase-AST) within 30 days of study enrollment; (Informed Consent Form signed) * No history of hyponatremia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Urinary 2OHE1:16alpha OHE1 ratio | Up to 18 months | estrogen metabolites measured in ng/100ul; this outcome will also be reported as a ratio |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma TAM metabolites (ng/mL) | Up to 18 months | measures of 4 primary metabolites (UCSF) |
| Serum Estrogen (estradiol) (pg/mL) | Up to 18 months | measured at U Michigan |
| Self reported vaginal bleeding | Up to 24 months | If vaginal ultrasound is available via medical records, toxicity will be addressed through endometrial evaluation. Otherwise, evaluation will be based on self report. |
| mammographic density | up to 18 months | assessed by fat:water ratio magnetic resonance imaging AND mammographic density from clinical mammograms |
Countries
United States
Outcome results
None listed