Prostate Cancer
Conditions
Keywords
recurrent prostate cancer, stage I prostate cancer, stage II prostate cancer, stage III prostate cancer, adenocarcinoma of the prostate, stage IV prostate cancer
Brief summary
RATIONALE: Diindolylmethane may slow the growth of prostate cancer cells. PURPOSE: This phase I trial is studying the side effects and best dose of diindolylmethane in treating patients with nonmetastatic prostate cancer that has not responded to previous hormone therapy.
Detailed description
OBJECTIVES: Primary * Establish the maximum tolerated dose, dose-limiting toxicity, and a recommended phase II dose of absorption-enhanced diindolylmethane (BioResponse-DIM\^® \[BR-DIM\]) in patients with nonmetastatic, hormone-refractory prostate cancer and rising serum prostate-specific antigen (PSA) levels. * Evaluate the toxicities of BR-DIM. Secondary * Evaluate the plasma pharmacokinetics of twice daily oral administration of BR-DIM in this patient population. * Evaluate the effect of BR-DIM supplementation on serum PSA level. * Correlate changes in expression levels of lymphocytes NF-kB with serum PSA levels in patients taking BR-DIM supplementation. * Determine quality of life measures in patients taking BR-DIM supplementation. OUTLINE: This is an open-label, dose-escalation study. Patients receive oral absorption-enhanced absorption-enhanced diindolylmethane (BioResponse-DIM\^® \[BR-DIM\]) twice daily on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of BR-DIM until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD. Quality of life is assessed at baseline, on day 1 of each course, and at the completion of study therapy. PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.
Interventions
DRUGBR-DIM
75 mg orally (po) twice daily. May continue treatment for 12 months, however patients will be taken off study if their disease progresses, or have intolerable side effects.
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 No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically proven adenocarcinoma of the prostate * Prostate specific antigen (PSA)-only failure after local therapy (surgery, radiation therapy, brachytherapy, or cryotherapy) * Rising PSA despite androgen-deprivation therapy with castrate levels of testosterone (\< 50 ng/dL) * Two successive rising PSA levels at least 1 week apart * PSA ≥ 5 ng/mL * Patients with a history of combined hormonal therapy must continue luteinizing-hormone releasing-hormone agonist treatment but must demonstrate rising PSA after anti-androgen withdrawal * No evidence of distant metastasis by bone scan and CT scan * No known brain metastases requiring active therapy PATIENT CHARACTERISTICS: * ECOG performance status ≤ 3 * Life expectancy ≥ 12 weeks * Absolute neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Hemoglobin ≥ 8.0 g/dL * Total bilirubin ≤ 1.5 times upper limit of normal (ULN) * SGOT and/or SGPT ≤ 2.5 times ULN AND alkaline phosphatase normal OR alkaline phosphatase ≤ 4 times ULN AND SGOT and/or SGPT normal * Creatinine clearance ≥ 60 mL/min OR creatinine normal * Fertile patients must use effective contraception * None of the following conditions within the past 6 months: * Myocardial infarction * Severe or unstable angina * Symptomatic congestive heart failure * Cerebrovascular accident or transient ischemic attack * Coronary/peripheral artery bypass grafting * No other severe acute or chronic medical or psychiatric condition or laboratory abnormality that would preclude study participation PRIOR CONCURRENT THERAPY: * See Disease Characteristics * At least 28 days since prior radiotherapy * At least 28 days since prior investigational agents for treatment of prostate cancer * At least 4 weeks since prior flutamide * At least 6 weeks since prior bicalutamide * No other concurrent antineoplastic agents * No concurrent warfarin-related anticoagulants * No concurrent proton-pump inhibitor drugs for gastroesophageal reflux disease (e.g., rabeprazole, esomeprazole magnesium, lansoprazole, omeprazole, or pantoprazole sodium) * No concurrent micronutrient supplements or dietary soy products * One daily multivitamin allowed
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum tolerated dose (MTD), Dose limiting toxicity (DLT) & toxicities during study and for 30 days after | During study and for 30 days after |
Secondary
| Measure | Time frame |
|---|---|
| Plasma pharmacokinetics as measured by occurrences of toxicity | At baseline; Cycle 1 Day 1 at 20, 60, 120, 180, 240, and 480 minutes |
| Serum prostate specific antigen as measured by complete plasma concentration-time profile | At baseline, Day 1 of each cycle and at study termination |
| Correlate changes in expression levels of NF-kB lymphocytes in with serum prostate specific antigen levels by serum prostate specific antigen level | At baseline, Cycle 2 and study termination |
| Quality of life (QOL) by Life Orient. Test-Rev., Duke-UNC Func. Social Support Questionnaire, EORTC QOL questionnaire, QLQ-PR25 questionnaire, and the Hosp. Anxiety & Depression Scale | At baseline, day 1 of each cycle and study termination |
Countries
United States
Outcome results
None listed