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
Study Overview
Status
Conditions
Detailed 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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Wisconsin
-
Madison, Wisconsin, United States, 53792
- University of Wisconsin Hospital and Clinics
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: 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.
|
Correlative studies
Correlative studies
Other Names:
Undergo surgical resection
Given PO
Other Names:
|
|
Experimental: Arm II
Patients receive high-dose, nutritional-grade oral DIM twice daily as in arm I.
|
Correlative studies
Correlative studies
Other Names:
Undergo surgical resection
Given PO
Other Names:
|
|
Placebo Comparator: 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.
|
Correlative studies
Correlative studies
Other Names:
Undergo surgical resection
Given PO
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Tissue levels of DIM
Time Frame: Up to 5 years
|
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
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Urinary 2-hydroxyestrone/16-hydroxyestrone ratio
Time Frame: Up to 5 years
|
Will be summarized by treatment arm with descriptive statistics.
|
Up to 5 years
|
|
Total PSA
Time Frame: Up to 5 years
|
Will be summarized by treatment arm with descriptive statistics.
|
Up to 5 years
|
|
Serum testosterone
Time Frame: Up to 5 years
|
Will be summarized by treatment arm with descriptive statistics.
|
Up to 5 years
|
|
IGF1:IGFBP-3 ratio
Time Frame: Up to 5 years
|
Will be summarized by treatment arm with descriptive statistics.
|
Up to 5 years
|
|
Tissue measures of messenger RNA of CYPs (CYP1A2, CYP1A1, CYP2B1, CYP3A)
Time Frame: Up to 5 years
|
Will be summarized by treatment arm with descriptive statistics.
|
Up to 5 years
|
|
DIM blood steady-state concentrations
Time Frame: Up to 5 years
|
Will be summarized by treatment arm with descriptive statistics.
|
Up to 5 years
|
|
Measures of androgen receptor, PSA, Ki-67, caspase 3, and TUNEL
Time Frame: Up to 5 years
|
Will be summarized by treatment arm with descriptive statistics.
|
Up to 5 years
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Jason Gee, University of Wisconsin, Madison
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- NCI-2009-00905
- N01CN35153 (U.S. NIH Grant/Contract)
- CO05816
- CDR0000656281
- H2006-0255
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