Diindolylmethane in Treating Patients With Breast Cancer

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

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.

Study Overview

• Status: Completed
• Conditions: Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer
• Intervention / Treatment: Dietary supplement: diindolylmethane; Dietary supplement: placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 144
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85012
      • Arizona Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (antineoplastic therapy); Patients receive diindolylmethane (BioResponse) PO BID for approximately 18 months.	Dietary supplement: diindolylmethane; Given PO; Other Names: DIM
Placebo Comparator: Arm II (placebo); Patients receive placebo PO BID for approximately 18 months.	Dietary supplement: placebo; Given PO; Other Names: PLCB

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urinary 2OHE1:16alpha OHE1 ratio	estrogen metabolites measured in ng/100ul; this outcome will also be reported as a ratio	Up to 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma TAM metabolites (ng/mL)	measures of 4 primary metabolites (UCSF)	Up to 18 months
Serum Estrogen (estradiol) (pg/mL)	measured at U Michigan	Up to 18 months
Self reported vaginal bleeding	If vaginal ultrasound is available via medical records, toxicity will be addressed through endometrial evaluation. Otherwise, evaluation will be based on self report.	Up to 24 months
mammographic density	assessed by fat:water ratio magnetic resonance imaging AND mammographic density from clinical mammograms	up to 18 months

Collaborators and Investigators

• Sponsor: University of Arizona
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Cynthia Thomson, University of Arizona

Publications and helpful links

General Publications

• Thomson CA, Chow HHS, Wertheim BC, Roe DJ, Stopeck A, Maskarinec G, Altbach M, Chalasani P, Huang C, Strom MB, Galons JP, Thompson PA. A randomized, placebo-controlled trial of diindolylmethane for breast cancer biomarker modulation in patients taking tamoxifen. Breast Cancer Res Treat. 2017 Aug;165(1):97-107. doi: 10.1007/s10549-017-4292-7. Epub 2017 May 30.

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): July 31, 2016

Study Registration Dates

• First Submitted: July 6, 2011
• First Submitted That Met QC Criteria: July 11, 2011
• First Posted (Estimate): July 12, 2011

Study Record Updates

• Last Update Posted (Actual): November 6, 2017
• Last Update Submitted That Met QC Criteria: October 31, 2017
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Protective Agents; Anticarcinogenic Agents; 3,3'-diindolylmethane
• Other Study ID Numbers: 10-0366-04; NCI-2011-00710 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); R01CA149417-01A1 (U.S. NIH Grant/Contract)