Diindolylmethane in Treating Patients With Breast Cancer
|Stage IA Breast Cancer Stage IB Breast Cancer Stage II Breast Cancer Stage IIIA Breast Cancer||Dietary Supplement: diindolylmethane Dietary Supplement: placebo||Phase 2 Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Investigator)
Primary Purpose: Treatment
|Official Title:||Evaluation of Diindolylmethane Supplementation to Modulate Tamoxifen Efficacy in Breast Cancer The Diindolylmethane Efficacy Study|
- Urinary 2OHE1:16alpha OHE1 ratio [ Time Frame: Up to 18 months ]estrogen metabolites measured in ng/100ul; this outcome will also be reported as a ratio
- Plasma TAM metabolites (ng/mL) [ Time Frame: Up to 18 months ]measures of 4 primary metabolites (UCSF)
- Serum Estrogen (estradiol) (pg/mL) [ Time Frame: Up to 18 months ]measured at U Michigan
- Self reported vaginal bleeding [ Time Frame: 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 [ Time Frame: up to 18 months ]assessed by fat:water ratio magnetic resonance imaging AND mammographic density from clinical mammograms
|Study Start Date:||February 2011|
|Estimated Study Completion Date:||July 2016|
|Primary Completion Date:||September 2014 (Final data collection date for primary outcome measure)|
Experimental: Arm I (antineoplastic therapy)
Patients receive diindolylmethane (BioResponse) PO BID for approximately 18 months.
Dietary Supplement: diindolylmethane
Other Name: DIM
Placebo Comparator: Arm II (placebo)
Patients receive placebo PO BID for approximately 18 months.
Dietary Supplement: placebo
Other Name: PLCB
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01391689
|United States, Arizona|
|Arizona Cancer Center|
|Tucson, Arizona, United States, 85012|
|Principal Investigator:||Cynthia Thomson||University of Arizona|