Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Diindolylmethane in Treating Patients With Nonmetastatic Prostate Cancer That Has Not Responded To Previous Hormone Therapy

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Closed	18 and over	NCI	WSU-D-2979 WSU-0507002581, NCT00305747

Objectives

Primary

1. 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.
2. Evaluate the toxicities of BR-DIM.

Secondary

1. Evaluate the plasma pharmacokinetics of twice daily oral administration of BR-DIM in this patient population.
2. Evaluate the effect of BR-DIM supplementation on serum PSA level.
3. Correlate changes in expression levels of lymphocytes NF-kB with serum PSA levels in patients taking BR-DIM supplementation.
4. Determine quality of life measures in patients taking BR-DIM supplementation.

Entry 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

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

Patient Characteristics:

• ECOG performance status ≤ 3
• Life expectancy ≥ 12 weeks
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• 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

Expected Enrollment

A total of 36 patients will be accrued for this study.

Outcomes

Maximum tolerated dose during study and for 30 days after
Dose limiting toxicity during study and for 30 days after
Toxicity during study and for 30 days after

Plasma pharmacokinetics as measured by occurrences of toxicity at baseline, 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 course, 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, second course, 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 course, and study termination

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.

Trial Contact Information

Trial Lead Organizations

Barbara Ann Karmanos Cancer Institute

Elisabeth Heath, MD, Protocol chair		Ph: 313-576-8715; 800-527-6266 Email: heathe@karmanos.org

Registry Information
Official Title		Phase I Study of Bioresponse-dim® in Non-Metastatic, Hormone-Refractory Prostate Cancer Patients with Rising Serum PSA
Trial Start Date		2005-08-24
Trial Completion Date		2013-08-24 (estimated)
Registered in ClinicalTrials.gov		NCT00305747
Date Submitted to PDQ		2005-12-05
Information Last Verified		2008-08-23
NCI Grant/Contract Number		CA22453