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

Prostate Cancer Clinical Trial

Official title:

Phase I Study of Bioresponse-dim in Non-Metastatic, Hormone-Refractory Prostate Cancer Patients With Rising Serum PSA

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00305747
• Other study ID #: CDR0000462637
• Secondary ID: P30CA022453WSU-D
• Status: Completed
• Phase: Phase 1
• First received: March 21, 2006
• Last updated: January 14, 2014
• Start date: August 2005
• Est. completion date: September 2010

Study information

• Verified date: January 2014
• Source: Barbara Ann Karmanos Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: September 2010
• Est. primary completion date: September 2010
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Weisberg Cancer Treatment Center	Detroit	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
Barbara Ann Karmanos Cancer Institute	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose (MTD), Dose limiting toxicity (DLT) & toxicities during study and for 30 days after		During study and for 30 days after	Yes
Secondary	Plasma pharmacokinetics as measured by occurrences of toxicity		At baseline; Cycle 1 Day 1 at 20, 60, 120, 180, 240, and 480 minutes	Yes
Secondary	Serum prostate specific antigen as measured by complete plasma concentration-time profile		At baseline, Day 1 of each cycle and at study termination	No
Secondary	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	No
Secondary	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	No