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Diindolylmethane in Treating Patients With Breast Cancer

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ClinicalTrials.gov Identifier: NCT01391689
Recruitment Status : Completed
First Posted : July 12, 2011
Last Update Posted : November 6, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Arizona

Tracking Information
First Submitted Date  ICMJE July 6, 2011
First Posted Date  ICMJE July 12, 2011
Last Update Posted Date November 6, 2017
Study Start Date  ICMJE February 2011
Actual Primary Completion Date September 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 3, 2014)
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
Original Primary Outcome Measures  ICMJE
 (submitted: July 11, 2011)
Mammographic Density [ Time Frame: Up to 18 months ]
MRI imaging will be performed to assess mammographic density.
Change History Complete list of historical versions of study NCT01391689 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 3, 2014)
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: July 11, 2011)
  • Urinary 20HE1:16alpha OHE1 ratio [ Time Frame: Up to 24 months. ]
    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 ]
  • Serum Estrogen (estradiol) (pg/mL) [ Time Frame: Up to 18 months ]
  • 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Diindolylmethane in Treating Patients With Breast Cancer
Official Title  ICMJE Evaluation of Diindolylmethane Supplementation to Modulate Tamoxifen Efficacy in Breast Cancer The Diindolylmethane Efficacy Study
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Stage IA Breast Cancer
  • Stage IB Breast Cancer
  • Stage II Breast Cancer
  • Stage IIIA Breast Cancer
Intervention  ICMJE
  • Dietary Supplement: diindolylmethane
    Given PO
    Other Name: DIM
  • Dietary Supplement: placebo
    Given PO
    Other Name: PLCB
Study Arms  ICMJE
  • Experimental: Arm I (antineoplastic therapy)
    Patients receive diindolylmethane (BioResponse) PO BID for approximately 18 months.
    Intervention: Dietary Supplement: diindolylmethane
  • Placebo Comparator: Arm II (placebo)
    Patients receive placebo PO BID for approximately 18 months.
    Intervention: Dietary Supplement: placebo
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 3, 2014)
144
Original Estimated Enrollment  ICMJE
 (submitted: July 11, 2011)
170
Actual Study Completion Date  ICMJE July 31, 2016
Actual Primary Completion Date September 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 19 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01391689
Other Study ID Numbers  ICMJE 10-0366-04
NCI-2011-00710 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
R01CA149417-01A1 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Arizona
Study Sponsor  ICMJE University of Arizona
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Cynthia Thomson University of Arizona
PRS Account University of Arizona
Verification Date April 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP