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

Barbara Ann Karmanos Cancer Institute

Status and phase: Completed; Phase 1

Conditions: Prostate Cancer

Treatments: Drug: BR-DIM

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00305747

WSU-0507002581

WSU-D-2979

P30CA022453 (U.S. NIH Grant/Contract)

CDR0000462637

Details and patient eligibility

About

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.

Full 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.

Enrollment: 12 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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12 participants in 1 patient group

BR-DIM

Experimental group

Description:

BR-DIM will be administered at a starting dose of 75 mg po twice daily. Patients will be instructed to take tablets twice daily with 8 ozs. of water, with/without food. A study calendar will be provided and patients will be asked to fill the appropriate boxes when they take their study capsules. One treatment cycle is 28 days.

Treatment:

Drug: BR-DIM