Diindolylmethane in Treating Patients With Breast Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by University of Arizona
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Arizona
ClinicalTrials.gov Identifier:
NCT01391689
First received: July 6, 2011
Last updated: March 20, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Ductal Breast Carcinoma in Situ
Lobular Breast Carcinoma in Situ
Recurrent Breast Cancer
Stage IA Breast Cancer
Stage IB Breast Cancer
Stage II Breast Cancer
Stage IIIA Breast Cancer
Drug: diindolylmethane
Other: placebo
Other: questionnaire administration
Procedure: digital mammography
Procedure: magnetic resonance imaging
Other: biomarker analysis of blood and urine
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Evaluation of Diindolylmethane Supplementation to Modulate Tamoxifen Efficacy in Breast Cancer The Diindolylmethane Efficacy Study

Resource links provided by NLM:


Further study details as provided by University of Arizona:

Primary Outcome Measures:
  • Mammographic Density [ Time Frame: Up to 18 months ] [ Designated as safety issue: No ]
    MRI imaging will be performed to assess mammographic density.


Secondary Outcome Measures:
  • Urinary 20HE1:16alpha OHE1 ratio [ Time Frame: Up to 24 months. ] [ Designated as safety issue: No ]
    Estrogen metabolites are often singly measured in units of ng/100ul, however the ratio is specified in the protocol and this outcome will be reported as a ratio.

  • Plasma TAM metabolites (ng/mL) [ Time Frame: Up to 18 months ] [ Designated as safety issue: No ]
  • Serum Estrogen (estradiol) (pg/mL) [ Time Frame: Up to 18 months ] [ Designated as safety issue: No ]
  • Self reported vaginal bleeding [ Time Frame: Up to 24 months ] [ Designated as safety issue: Yes ]
    If vaginal ultrasound is available via medical records, toxicity will be addressed through endometrial evaluation. Otherwise, evaluation will be based on self report.


Estimated Enrollment: 170
Study Start Date: February 2011
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (antineoplastic therapy)
Patients receive diindolylmethane PO BID for approximately 18 months.
Drug: diindolylmethane
Given PO
Other Name: DIM
Other: questionnaire administration
Ancillary studies
Procedure: digital mammography
Correlative studies
Procedure: magnetic resonance imaging
Correlative studies
Other Names:
  • MRI
  • NMR imaging
  • NMRI
  • nuclear magnetic resonance imaging
Other: biomarker analysis of blood and urine
Correlative studies
Other Name: Assays used in correlative studies include gas chromatagraphy, mass spectometry, liquid chromatography, and ELISA
Placebo Comparator: Arm II (placebo)
Patients receive placebo PO BID for approximately 18 months.
Other: placebo
Given PO
Other Name: PLCB
Other: questionnaire administration
Ancillary studies
Procedure: digital mammography
Correlative studies
Procedure: magnetic resonance imaging
Correlative studies
Other Names:
  • MRI
  • NMR imaging
  • NMRI
  • nuclear magnetic resonance imaging
Other: biomarker analysis of blood and urine
Correlative studies
Other Name: Assays used in correlative studies include gas chromatagraphy, mass spectometry, liquid chromatography, and ELISA

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.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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)
  • Breast cancer surgery resulted in intact contralateral breast for mammography/MRI evaluation
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01391689

Locations
United States, Arizona
Arizona Cancer Center Recruiting
Tucson, Arizona, United States, 85012
Contact: Cynthia A Thomson    520-626-1565    cthomson@email.arizona.edu   
Principal Investigator: Cynthia A Thomson         
Sponsors and Collaborators
University of Arizona
Investigators
Principal Investigator: Cynthia Thomson University of Arizona
  More Information

No publications provided

Responsible Party: University of Arizona
ClinicalTrials.gov Identifier: NCT01391689     History of Changes
Other Study ID Numbers: 10-0366-04, NCI-2011-00710
Study First Received: July 6, 2011
Last Updated: March 20, 2014
Health Authority: United States: Federal Government
United States: Institutional Review Board

Additional relevant MeSH terms:
Breast Neoplasms
Carcinoma
Carcinoma in Situ
Carcinoma, Intraductal, Noninfiltrating
Carcinoma, Ductal, Breast
Carcinoma, Lobular
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adenocarcinoma
Neoplasms, Ductal, Lobular, and Medullary
Carcinoma, Ductal

ClinicalTrials.gov processed this record on August 21, 2014