Prostate Cancer
Conditions
Keywords
adenocarcinoma of the prostate, stage I prostate cancer, stage II prostate cancer
Brief summary
RATIONALE: The use of diindolylmethane, a substance found in cruciferous vegetables, may slow the growth of tumor cells. PURPOSE: This phase II trial is studying how well diindolylmethane works in treating patients with stage I or stage II prostate cancer undergoing radical prostatectomy.
Detailed description
OBJECTIVES: Primary * To measure the level of diindolylmethane in prostate tissue after treatment with oral microencapsulated diindolylmethane (B-DIM) in patients with stage I or II adenocarcinoma of the prostate undergoing radical prostatectomy. Secondary * To measure serum biomarkers (e.g., total PSA, serum testosterone, and diindolylmethane levels) pre- and post-treatment with B-DIM. * To measure tissue biomarkers (e.g., androgen receptor, NF-κB, and PSA) pre- and post-treatment with B-DIM. OUTLINE: This is a multicenter study. Patients receive oral microencapsulated diindolylmethane (B-DIM) twice daily for 14-72 days in the absence of disease progression or unacceptable toxicity. Patients then undergo radical prostatectomy 1 day after the last dose of B-DIM. Patients undergo blood and tissue sample collection for correlative laboratory studies. Blood samples are analyzed for serum PSA, testosterone, and diindolylmethane levels by high performance liquid chromatography and tandem mass spectrometry (LC-MS/MS). Tissue samples are analyzed for diindolylmethane concentration by LC-MS/MS and for androgen receptor, activated NF-κB (p65 antibody), and PSA expression by IHC.
Interventions
DRUGB-Dim
B-DIM 225 mg orally twice daily x 14-72 days (based on scheduling of surgery)
PROCEDURERadical Prosatectomy
Sponsors
National Cancer Institute (NCI)
Barbara Ann Karmanos Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed adenocarcinoma of the prostate * Stage I or II (T1-T2 a, b, or c) disease * Disease confined to the prostate by clinical judgment of the surgeon * Deemed an appropriate candidate for surgery by clinical judgment of the surgeon PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * ANC ≥ 1,500/mm³ * Platelet count ≥ 100,000/mm³ * Hemoglobin ≥ 8.0 g/dL * Total bilirubin ≤ 1.5 times upper limit of normal (ULN) * AST and/or ALT ≤ 2.5 times ULN if alkaline phosphatase normal OR alkaline phosphatase ≤ 4 times ULN if AST and/or ALT normal * Serum creatinine ≤ 2.0 mg/dL * No history of allergic reactions attributed to compounds of similar chemical or biological composition to oral microencapsulated diindolylmethane * No concurrent uncontrolled illness including, but not limited to, any of the following: * Ongoing or active infection * Symptomatic congestive hart failure * Unstable angina pectoris * Cardiac arrhythmia * Psychiatric illness or social situation that would limit compliance with study requirements PRIOR CONCURRENT THERAPY: * No prior chemotherapy, hormonal therapy, brachytherapy, cryotherapy, external beam radiotherapy, or other therapy for prostate cancer * No concurrent micronutrient supplements or dietary soy products * No concurrent systemic therapy for any other cancer * No concurrent p450 inducers or inhibitors (e.g., carbamazepine, clarithromycin, fluconazole, fosphenytoin, itraconazole, ketoconazole, phenobarbital, phenytoin, rifabutin, or rifampin) * No concurrent finasteride or dutasteride * No other concurrent investigational or commercial agents or therapies for the malignancy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mean Level of Diindolylmethane in Prostate Tissue After Treatment | Within the first 24 months after radical prostatectomy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Levels of PSA, Testosterone, and Diindolylmethane | Pre and post radical prostatectomy | Serum levels of PSA, testosterone, and diindolylmethane (DIM) |
| Levels of Androgen Receptor in Prostate Tissue | Pre and post radical prostatectomy | Levels of androgen receptor in prostate tissue as measured by AR score (intensity x % cells stained), higher scores indicate higher levels of androgen receptor in prostate tissue. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| B-Dim, Radical Prosatectomy B-DIM 225 mg orally twice daily x 14-72 days (based on scheduling of surgery)
Radical Prostatectomy
B-Dim: B-DIM 225 mg orally twice daily x 14-72 days (based on scheduling of surgery)
Radical Prosatectomy | 41 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Change in surg date | 1 |
| Overall Study | Inelig. due to contraindication of med | 1 |
| Overall Study | Not enough oral meds before surgery | 3 |
| Overall Study | Problems swallowing oral meds. | 1 |
| Overall Study | Stopped meds due to headaches | 1 |
| Overall Study | Surgery aborted | 2 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | B-Dim, Radical Prosatectomy |
|---|---|
| Age, Continuous | 58 years |
| Region of Enrollment United States | 41 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 41 |
| serious Total, serious adverse events | 2 / 41 |
Outcome results
Primary
Mean Level of Diindolylmethane in Prostate Tissue After Treatment
Time frame: Within the first 24 months after radical prostatectomy.
Population: Patients that were eligible, evaluable, and compliant
| Arm | Measure | Value (MEAN) |
|---|---|---|
| B-Dim, Radical Prosatectomy | Mean Level of Diindolylmethane in Prostate Tissue After Treatment | 14.2 ng/g |
Secondary
Levels of Androgen Receptor in Prostate Tissue
Levels of androgen receptor in prostate tissue as measured by AR score (intensity x % cells stained), higher scores indicate higher levels of androgen receptor in prostate tissue.
Time frame: Pre and post radical prostatectomy
Population: All enrolled patients except for one patient who was deemed ineligible due to a disallowed concomitant medication and for one patient whose prostatectomy was cancelled because of adhesions found at the time of surgery.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| B-Dim, Radical Prosatectomy | Levels of Androgen Receptor in Prostate Tissue | Pre-BR-DIM Androgen Receptor | 278 AR score (intensity x % cells stained) |
| B-Dim, Radical Prosatectomy | Levels of Androgen Receptor in Prostate Tissue | Post-BR-DIM Androgen Receptor | 245 AR score (intensity x % cells stained) |
Secondary
Serum Levels of PSA, Testosterone, and Diindolylmethane
Serum levels of PSA, testosterone, and diindolylmethane (DIM)
Time frame: Pre and post radical prostatectomy
Population: All enrolled patients except for one patient who was deemed ineligible due to a disallowed concomitant medication and for one patient whose prostatectomy was cancelled because of adhesions found at the time of surgery.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| B-Dim, Radical Prosatectomy | Serum Levels of PSA, Testosterone, and Diindolylmethane | Pre-treatment PSA | 6.4 ng/ml |
| B-Dim, Radical Prosatectomy | Serum Levels of PSA, Testosterone, and Diindolylmethane | Post-treatment PSA | 5.8 ng/ml |
| B-Dim, Radical Prosatectomy | Serum Levels of PSA, Testosterone, and Diindolylmethane | Pre-treatment Testosterone | 301 ng/ml |
| B-Dim, Radical Prosatectomy | Serum Levels of PSA, Testosterone, and Diindolylmethane | Post-treatment Testosterone | 388 ng/ml |
| B-Dim, Radical Prosatectomy | Serum Levels of PSA, Testosterone, and Diindolylmethane | Pre-treatment DIM | 0.0 ng/ml |
| B-Dim, Radical Prosatectomy | Serum Levels of PSA, Testosterone, and Diindolylmethane | Post-treatment DIM | 7.5 ng/ml |