Diindolylmethane in Treating Patients Undergoing Surgery for Stage I or Stage II Prostate Cancer - Full Text View

Sponsor:	University of Wisconsin, Madison
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00450229

Purpose

RATIONALE: Giving diindolylmethane, a substance found in cruciferous vegetables, may help doctors learn more about how diindolylmethane is used by the body.

PURPOSE: 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.

Condition	Intervention	Phase
Prostate Cancer	Drug: oral microencapsulated diindolylmethane Genetic: gene expression analysis Genetic: polymerase chain reaction Genetic: polymorphism analysis Other: immunoenzyme technique Other: immunohistochemistry staining method Other: laboratory biomarker analysis Other: mass spectrometry Other: pharmacological study Procedure: biopsy Procedure: conventional surgery Procedure: neoadjuvant therapy	Phase I

Study Type:	Interventional
Study Design:	Treatment, Randomized, Placebo Control
Official Title:	Phase Ib Placebo-Controlled Trial of Diindolylmethane (BR-DIM) in the Study of Modulation of Intermediate Endpoint Markers in Patients With Prostate Cancer Who Are Undergoing Prostatectomy

Resource links provided by NLM:

MedlinePlus related topics: Cancer Prostate Cancer Surgery

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Tissue levels of diindolylmethane (DIM) as measured by liquid chromatography/mass spectrometry (LC/MS) assay after completion of study treatment [ Designated as safety issue: No ]

Secondary Outcome Measures:

Ratio of urinary 2-hydroxyestrone:16-hydroxyestrone as measured by LC/MS assay at 2 weeks and after completion of study treatment [ Designated as safety issue: No ]
Ratio of plasma insulin-like growth factor (IGF)-1:IGF binding protein-3 and plasma total prostate-specific antigen (PSA) as measured by ELISA at 2 weeks and after completion of study treatment [ Designated as safety issue: No ]
Serum testosterone as measured at 2 weeks and after completion of study treatment [ Designated as safety issue: No ]
mRNA expression of CYP1A1, CYP1A2, CYP2B1, and CYP3A enzymes in serum and fresh frozen tissue as measured by semiquantitative real-time polymerase chain reaction [ Designated as safety issue: No ]
Polymorphisms of CYP1A1, CYP1A2, CYP2B1, and CYP3A enzymes in polymorphonuclear leukocytes (PMNs) as measured by genotyping at 2 weeks and after completion of study treatment [ Designated as safety issue: No ]
DIM blood steady-state concentrations as measured by LC/MS at 2 weeks and after completion of study treatment [ Designated as safety issue: No ]
PSA, androgen receptor, Ki-67, and caspase 3 as measured by immunohistochemistry at 2 weeks and after completion of study treatment [ Designated as safety issue: No ]
Safety as measured by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]

Estimated Enrollment:	45
Study Start Date:	October 2006

Detailed Description:

OBJECTIVES:

Primary

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

Compare the ratio of urinary 2-hydroxyestrone:16-hydroxyestrone in patients treated with these regimens.
Compare plasma levels of total prostate-specific antigen (PSA) in patients treated with these regimens.
Compare serum testosterone levels in patients treated with these regimens.
Compare the ratio of plasma insulin-like growth factor (IGF)-1:IGF binding protein-3 in patients treated with these regimens.
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.
Compare DIM blood steady-state concentrations in patients treated with these regimens.
Identify polymorphisms of CYP1A1, CYP1A2, CYP2B1, and CYP3A in circulating PMNs in patients treated with these regimens.
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.

PROJECTED ACCRUAL: A total of 45 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

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

PATIENT CHARACTERISTICS:

ECOG performance status (PS) 0-1 OR Karnofsky PS 80-100%
WBC normal
Platelet count ≥ 100,000/mm³
Hemoglobin ≥ 10 g/dL
Bilirubin normal
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

PRIOR CONCURRENT THERAPY:

No prior chemotherapy, hormonal therapy, brachytherapy, or external radiotherapy for prostate cancer
At least 21 days since prior surgery
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00450229

Locations

United States, Alabama
Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham
Birmingham, Alabama, United States, 35294
United States, California
South Coast Urological Medical Group
Laguna Hills, California, United States, 92653
United States, New York
James P. Wilmot Cancer Center at University of Rochester Medical Center
Rochester, New York, United States, 14642
United States, Texas
Urology San Antonio, PA - Fredericksburg
San Antonio, Texas, United States, 78229
United States, Wisconsin
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792-6164

Sponsors and Collaborators

University of Wisconsin, Madison

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Jason R. Gee, MD

University of Wisconsin, Madison

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000534115, WCCC-CO05186, WCCC-H2006-0255, WCCC-06-1270-02
Study First Received:	March 20, 2007
Last Updated:	February 24, 2009
ClinicalTrials.gov Identifier:	NCT00450229 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

adenocarcinoma of the prostate
stage I prostate cancer
stage II prostate cancer

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Site
Prostatic Diseases
Genital Neoplasms, Male

Urogenital Neoplasms
Genital Diseases, Male
Prostatic Neoplasms

ClinicalTrials.gov processed this record on November 27, 2009