Antineoplastic Agents

All Drugs and Chemicals

3,3'-diindolylmethane

Protective Agents

Participants receive a single dose of diindolylmethane PO on day 1.

Participants receive a single dose of placebo orally (PO) on day 1.

diindolylmethane

placebo

pharmacological study

laboratory biomarker analysis

quality-of-life assessment

Aryeh Hurwitz

This phase I clinical trial studies the side effects and best dose of diindolylmethane in preventing cancer in healthy volunteers. Diindolylmethane is formed in the stomachs of people who eat a chemical that is normally found in vegetables, including cabbage, broccoli, Brussels sprouts, cauliflower, and watercress. Diindolylmethane may prevent the development of cancer.

PRIMARY OBJECTIVES:

I. To determine single oral doses of 3,3' di-indolylmethane (DIM) (diindolylmethane) that are safe and well- tolerated.

II. To determine the pharmacokinetics of these single oral doses of DIM.

OUTLINE: This is a dose-escalation study. Participants are randomized to 1 of 2 treatment arms.

ARM I: Participants receive a single dose of diindolylmethane orally (PO) on day 1.

ARM II: Participants receive a single dose of placebo orally (PO) on day 1.

After completion of study treatment, participants are followed up on days 2, 3, and 6.

Diindolylmethane in Preventing Cancer in Healthy Volunteers

Phase I Ascending Single Dose Pharmacokinetics (PK) and Safety Study of 3,3' Di-indolylmethane (DIM)

Frequencies and percents will be used to summarize the toxicities seen at each dose level and overall. Descriptive statistics will be calculated on all variables of interest: frequencies and percentages will be used to summarize categorical variables and medians, and ranges will summarize quantitative variables.

Pharmacokinetic parameters such as half-life, maximum concentration (Cmax), time of Cmax (Tmax), and area under the concentration-time curve (AUC) will be calculated for all subjects who complete the study. It is anticipated that a one-compartment elimination model will fit the data. These parameters will be summarized at each dose and overall with median and ranges.

National Cancer Institute (NCI)

Symptoms and General Pathology

All Conditions

Neoplasms

Rare Diseases

Recurrence

Papilloma

Neoplasms, Squamous Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Laryngeal Papillomatosis

once-time 585 nm pulsed dye laser (PDL) treatment on the lesions, immediately followed by 3-month oral taking diindolylmethane (DIM, at 1.2-1.75mg/kg/day), in 15 subjects

once-time PDL treatment on the lesions, then followed by 3-month oral taking DIM placebo, in other 15 subjects

diindolylmethane (DIM)

585 nm pulsed dye laser

Zhi Wang, MD

This study will determine efficacy of a new and combined treatment of laryngeal recurrent respiratory papillomatosis (RRP), by using a 585 nm pulsed dye laser (PDL) and a dietary supplement, diindolylmethane (DIM). We will compare this new treatment with PDL-only, in a total of 30 children (15 of each treatment), to determine whether this combined treatment would be effective and safe in preventing the RRP recurrence. This is the first study to combine PDL technique with DIM, to develop a new, voice-preserving and long-term effective method of managing laryngeal RRP in children.

Previous studies have demonstrated that PDL can be used to remove lesions on the vocal cords and elsewhere in the throat causing less damage to surface tissues than other commonly used lasers. In our proposed clinical study, we seek to compare treatment efficacy for RRP by combining PDL with DIM, versus PDL-only treatment, in a total of 30 children with laryngeal papilloma. We will determine whether this combined treatment would be effective and safe in preventing or delaying the RRP recurrence while preserving voice quality. 30 children will be divided randomly into two treatment groups, 15 in each. The experimental group will receive one-time PDL treatment, followed by 3-month oral administration of DIM and an additional 12 months with no treatment. The other group will be treated with PDL-only, as a control, and take a placebo pill for 3 months. All of the patients will be followed for a total of 15 months. We will compare lesion recurrence and laboratory tests between the two groups, to determine efficacy and safety of the new treatment. This is the first study to combine new PDL laser technique with DIM, to develop a new, voice-preserving and long-term effective method of managing laryngeal RRP in children.

laser only vs laser+ a dietary agent (DIM)

treatment to be selected based on a randomized number table, blinded to participants

New Therapy of Laryngeal Papilloma In Children

Voice Preserving Therapy of Laryngeal Papilloma In Children

no such meaningful data available due to insufficient recruitment

vocal lesion size and area after 5 month with surgery visible lesion found in \>50% of the treated tissue area, after surgery

determine side-effect by comparing Estradiol level in blood before and after treatment

National Institute on Deafness and Other Communication Disorders (NIDCD)

Boston University

Professor and Director

PDL+DIM Pill

once-time PDL treatment by PDL on the lesions, then followed by 3-month oral taking DIM placebo, in other 15 subjects

PDL+Placebo Pill

once-time 585 nm pulsed dye laser (PDL) treatment on the lesions, immediately followed by 3-month oral taking diindolylmethane (DIM, at 1.2-1.75mg/kg/day), in 15 subjects

diindolylmethane (DIM): 3-month DIM

585 nm pulsed dye laser: once-time PDL

once-time PDL treatment on the lesions, then followed by 3-month oral taking DIM placebo, in other 15 subjects

585 nm pulsed dye laser: once-time PDL

Total

Age, Categorical

Sex: Female, Male

United States

Region of Enrollment

There was only one participant due to difficulty in recruitment which resulted in early termination of the trial.

Intervention

Placebo

participants received at least one of two interventions

Number of Cases With Recurrence of Laryngeal Papilloma in 5 Months

failure for any meaningful analysis as only 1 participant in this study

Estradiol Level in Blood Pre Treatment

Estradiol Level in Blood Post Treatment

Overall Study

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Adenocarcinoma

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Patients receive low-dose, nutritional-grade oral diindolylmethane (DIM) twice daily for 21-28 days in the absence of disease progression or unacceptable toxicity. Treatment may continue for up to 60 days, if surgery is delayed.

Patients receive high-dose, nutritional-grade oral DIM twice daily as in arm I.

Patients receive oral placebo twice daily for 21-28 days in the absence of disease progression or unacceptable toxicity. Treatment may continue for up to 60 days, if surgery is delayed.

therapeutic conventional surgery

Jason Gee

Giving diindolylmethane, a substance found in cruciferous vegetables, may help doctors learn more about how diindolylmethane is used by the body. This randomized phase I trial is studying the side effects and best dose of diindolylmethane compared with a placebo in treating patients undergoing radical prostatectomy for stage I or stage II prostate cancer.

PRIMARY OBJECTIVES:

I. Compare neoadjuvant prostatic diindolylmethane (DIM\^) concentrations in patients with stage I or II adenocarcinoma of the prostate treated with DIM vs placebo prior to radical prostatectomy.

SECONDARY OBJECTIVES:

I. Compare the ratio of urinary 2-hydroxyestrone:16-hydroxyestrone in patients treated with these regimens.

II. Compare plasma levels of total prostate-specific antigen (PSA) in patients treated with these regimens.

III. Compare serum testosterone levels in patients treated with these regimens. IV. Compare the ratio of plasma insulin-like growth factor (IGF)-1:IGF binding protein-3 in patients treated with these regimens.

V. Compare cytochrome p450 mRNA expression of CYP1A1, CYP1A2, CYP2B1, and CYP3A enzymes in circulating polymorphonuclear leukocytes (PMNs) and in fresh frozen tissue in patients treated with these regimens.

VI. Compare DIM blood steady-state concentrations in patients treated with these regimens.

VII. Identify polymorphisms of CYP1A1, CYP1A2, CYP2B1, and CYP3A in circulating PMNs in patients treated with these regimens.

VIII. Compare tissue levels of PSA, androgen receptor, Ki-67, and caspase 3 in patients treated with these regimens.

OUTLINE:

This is a randomized, placebo-controlled, multicenter study. Patients are randomized to 1 of 3 treatment arms.

Arm I: Patients receive low-dose, nutritional-grade oral diindolylmethane (DIM) twice daily for 21-28 days in the absence of disease progression or unacceptable toxicity. Treatment may continue for up to 60 days, if surgery is delayed.

Arm II: Patients receive high-dose, nutritional-grade oral DIM twice daily as in arm I.

Arm III: Patients receive oral placebo twice daily for 21-28 days in the absence of disease progression or unacceptable toxicity. Treatment may continue for up to 60 days, if surgery is delayed.

Patients in all arms undergo surgical resection of their tumor within 1 day after completion of DIM or placebo.

Patients undergo blood, tissue, and urine sample collection periodically during study for immunohistochemical (IHC)/molecular analyses and pharmacokinetic and pharmacogenomic correlative studies. Patient specimens are assessed for DIM levels in plasma and tissue (by liquid chromatography/mass spectrometry \[LC/MS\]) and for biologic response to DIM (by TUNEL assay). Intermediate biomarkers of DIM activity are also assessed, including urinary 2-hydroxyestrone:16-hydroxyestrone ratio (by LC/MS assay), plasma total prostate-specific antigen (PSA), plasma insulin-like growth factor (IGF)-1:IGF binding protein-3 ratio (by ELISA), and tissue androgen receptor, PSA, Ki-67, and caspase 3 (by immunohistochemistry). Cytochrome p450 induction and gene expression (CYP1A1, CYP1A2, CYP2B1, CYP3A) are also assessed in tissue and plasma by semiquantitative real-time polymerase chain reaction.

Diindolylmethane in Treating Patients Undergoing Surgery for Stage I or Stage II Prostate Cancer

Phase Ib Placebo-Controlled Trial of Diindolylmethane (BR-DIM) in the Study of the Modulation of Intermediate Endpoint Markers in Patients With Prostate Cancer Who Are Undergoing Prostatectomy

The distribution of levels of DIM will be summarized by treatment arm with descriptive statistics. For the primary comparison between the placebo group and the DIM groups combined, tissue levels of DIM will be compared using Student t-test. In the case of violation of normality assumptions, an appropriate transformation of the data such as logarithm will be considered or a nonparametric test such as Wilcoxon rank-sum test will be used for comparison. A dose-response relation will be explored based on the analysis of covariance (ANCOVA).

Will be summarized by treatment arm with descriptive statistics.

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Bone Density Conservation Agents

Tamoxifen

Patients receive diindolylmethane (BioResponse) PO BID for approximately 18 months.

Patients receive placebo PO BID for approximately 18 months.

Cynthia Thomson

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.

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.

Diindolylmethane in Treating Patients With Breast Cancer

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

estrogen metabolites measured in ng/100ul; this outcome will also be reported as a ratio

If vaginal ultrasound is available via medical records, toxicity will be addressed through endometrial evaluation. Otherwise, evaluation will be based on self report.

assessed by fat:water ratio magnetic resonance imaging AND mammographic density from clinical mammograms

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Diindolylmethane in Preventing Cancer in Healthy Volunteers	NCT00784394	Healthy, no Evi...	diindolylmethan... placebo pharmacological... laboratory biom... quality-of-life...	18 Years - 70 Years	National Cancer Institute (NCI)
New Therapy of Laryngeal Papilloma In Children	NCT00591305	Papilloma	diindolylmethan... 585 nm pulsed d...	10 Years - 21 Years	Boston University
Diindolylmethane in Treating Patients Undergoing Surgery for Stage I or Stage II Prostate Cancer	NCT00450229	Adenocarcinoma ... Prostate Cancer Stage I Prostat... Stage II Prosta...	diindolylmethan... placebo therapeutic con... laboratory biom... pharmacological...	18 Years -	National Cancer Institute (NCI)
Diindolylmethane in Treating Patients With Breast Cancer	NCT01391689	Stage IA Breast... Stage IB Breast... Stage II Breast... Stage IIIA Brea...	diindolylmethan... placebo	19 Years -	University of Arizona
Diindolylmethane in Treating Patients With Breast Cancer	NCT01391689	Stage IA Breast... Stage IB Breast... Stage II Breast... Stage IIIA Brea...	diindolylmethan... placebo	19 Years -	University of Arizona
Diindolylmethane in Treating Patients Undergoing Surgery for Stage I or Stage II Prostate Cancer	NCT00450229	Adenocarcinoma ... Prostate Cancer Stage I Prostat... Stage II Prosta...	diindolylmethan... placebo therapeutic con... laboratory biom... pharmacological...	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for diindolylmethane