Diindolylmethane in Treating Patients Undergoing Surgery for Stage I or Stage II Prostate Cancer
- Conditions
- Stage I Prostate CancerStage II Prostate CancerAdenocarcinoma of the ProstateProstate Cancer
- Interventions
- Drug: diindolylmethaneDrug: placeboProcedure: therapeutic conventional surgeryOther: laboratory biomarker analysisOther: pharmacological study
- Registration Number
- NCT00450229
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 45
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm II therapeutic conventional surgery Patients receive high-dose, nutritional-grade oral DIM twice daily as in arm I. Arm I diindolylmethane 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 I pharmacological study 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 III laboratory biomarker analysis 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. Arm I laboratory biomarker analysis 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 diindolylmethane Patients receive high-dose, nutritional-grade oral DIM twice daily as in arm I. Arm III therapeutic conventional surgery 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. Arm III pharmacological study 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. Arm I therapeutic conventional surgery 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 laboratory biomarker analysis Patients receive high-dose, nutritional-grade oral DIM twice daily as in arm I. Arm II pharmacological study Patients receive high-dose, nutritional-grade oral DIM twice daily as in arm I. Arm III placebo 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.
- Primary Outcome Measures
Name Time Method Tissue levels of DIM 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).
- Secondary Outcome Measures
Name Time Method DIM blood steady-state concentrations Up to 5 years Will be summarized by treatment arm with descriptive statistics.
Tissue measures of messenger RNA of CYPs (CYP1A2, CYP1A1, CYP2B1, CYP3A) Up to 5 years Will be summarized by treatment arm with descriptive statistics.
Total PSA Up to 5 years Will be summarized by treatment arm with descriptive statistics.
Measures of androgen receptor, PSA, Ki-67, caspase 3, and TUNEL Up to 5 years Will be summarized by treatment arm with descriptive statistics.
Urinary 2-hydroxyestrone/16-hydroxyestrone ratio Up to 5 years Will be summarized by treatment arm with descriptive statistics.
Serum testosterone Up to 5 years Will be summarized by treatment arm with descriptive statistics.
IGF1:IGFBP-3 ratio Up to 5 years Will be summarized by treatment arm with descriptive statistics.
Trial Locations
- Locations (1)
University of Wisconsin Hospital and Clinics
🇺🇸Madison, Wisconsin, United States