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

Prostate Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00450229
• Other study ID #: NCI-2009-00905
• Secondary ID: CO05816CDR000065
• Status: Completed
• Phase: Phase 1
• First received: March 20, 2007
• Last updated: December 3, 2015
• Start date: February 2007
• Est. completion date: February 2010

Study information

• Verified date: May 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: February 2010
• Est. primary completion date: February 2010
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Criteria:

• Histologically confirmed adenocarcinoma of the prostate

• Clinical stage T1 or T2 a, b, or c (stage I-II disease)

• Disease is confined within the prostate gland

• Candidate for radical prostatectomy

• ECOG performance status (PS) 0-1 OR Karnofsky PS 80-100%

• WBC normal

• Platelet count >= 100,000/mm^3

• Hemoglobin >= 10 g/dL

• AST =< 1.5 times upper limit of normal

• Creatinine =< 2.0 mg/dL

• Fertile patients must use effective contraception

• No history of allergic reactions attributed to diindolylmethane (DIM^), any of the inactive ingredients contained in BioResponse-DIM^NG or placebo, or to compounds of similar chemical or biologic composition

• No concurrent uncontrolled illness including, but not limited to, any of the following: Ongoing or active infection, Symptomatic congestive heart failure, Unstable angina pectoris, Cardiac arrhythmia, No psychiatric illness or social situation that would preclude study compliance

• No prior chemotherapy, hormonal therapy, brachytherapy, or external radiotherapy for prostate cancer

• No concurrent nonsteroidal anti-inflammatory drugs, including acetylsalicylic acid, ibuprofen, naproxen sodium, or cyclooxygenase-2 inhibitors

• No concurrent systemic therapy for any other cancer

• No other concurrent investigational agents

• No concurrent p450 inducers or inhibitors, including any of the following:

Carbamazepine, Clarithromycin, Fluconazole, Fosphenytoin, Itraconazole, Ketoconazole, Phenobarbital, Phenytoin, Rifabutin, Rifampin

• No concurrent finasteride or dutasteride

• No more than 1 serving of cruciferous vegetables per day for duration of study

• Cruciferous vegetables include the following: broccoli, cauliflower, brussels sprouts, cabbage, arugula, watercress, bok-choy, turnip greens, mustard greens, collard greens, rutabaga, Napa or Chinese cabbage, radishes, turnips, kohlrabi, and kale

• Bilirubin normal

• At least 21 days since prior surgery

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Prostate
• Prostate Cancer
• Prostatic Neoplasms
• Stage I Prostate Cancer
• Stage II Prostate Cancer

Intervention

Drug:
• diindolylmethane
Given PO
• placebo
Given PO

Procedure:
• therapeutic conventional surgery
Undergo surgical resection

Other:
• laboratory biomarker analysis
Correlative studies
• pharmacological study
Correlative studies

Locations

Country	Name	City	State
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tissue levels of DIM	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).	Up to 5 years	No
Secondary	Urinary 2-hydroxyestrone/16-hydroxyestrone ratio	Will be summarized by treatment arm with descriptive statistics.	Up to 5 years	No
Secondary	Total PSA	Will be summarized by treatment arm with descriptive statistics.	Up to 5 years	No
Secondary	Serum testosterone	Will be summarized by treatment arm with descriptive statistics.	Up to 5 years	No
Secondary	IGF1:IGFBP-3 ratio	Will be summarized by treatment arm with descriptive statistics.	Up to 5 years	No
Secondary	Tissue measures of messenger RNA of CYPs (CYP1A2, CYP1A1, CYP2B1, CYP3A)	Will be summarized by treatment arm with descriptive statistics.	Up to 5 years	No
Secondary	DIM blood steady-state concentrations	Will be summarized by treatment arm with descriptive statistics.	Up to 5 years	No
Secondary	Measures of androgen receptor, PSA, Ki-67, caspase 3, and TUNEL	Will be summarized by treatment arm with descriptive statistics.	Up to 5 years	No