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

NCT ID: NCT00305747

Last Updated: 2014-01-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-08-31
• Study Completion Date: 2010-09-30

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.

Conditions

Prostate Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

BR-DIM

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.

Group Type: EXPERIMENTAL

BR-DIM

Intervention Type: DRUG

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.

Interventions

BR-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.

Intervention Type: DRUG

Other Intervention Names

oral microencapsulated diindolylmethane

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Barbara Ann Karmanos Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Elisabeth Heath

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Elisabeth I. Heath, MD

Role: STUDY_CHAIR

Barbara Ann Karmanos Cancer Institute

Locations

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Weisberg Cancer Treatment Center

Detroit, Michigan, United States

Countries

United States

Other Identifiers

P30CA022453

Identifier Type: NIH

Identifier Source: secondary_id

View Link

WSU-D-2979

Identifier Type: -

Identifier Source: secondary_id

WSU-0507002581

Identifier Type: -

Identifier Source: secondary_id

CDR0000462637

Identifier Type: -

Identifier Source: org_study_id