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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Elisabeth Heath, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier:
NCT00305747
First received: March 21, 2006
Last updated: January 14, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Prostate Cancer
Drug: BR-DIM
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Bioresponse-dim in Non-Metastatic, Hormone-Refractory Prostate Cancer Patients With Rising Serum PSA

Resource links provided by NLM:


Further study details as provided by Barbara Ann Karmanos Cancer Institute:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD), Dose limiting toxicity (DLT) & toxicities during study and for 30 days after [ Time Frame: During study and for 30 days after ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Plasma pharmacokinetics as measured by occurrences of toxicity [ Time Frame: At baseline; Cycle 1 Day 1 at 20, 60, 120, 180, 240, and 480 minutes ] [ Designated as safety issue: Yes ]
  • Serum prostate specific antigen as measured by complete plasma concentration-time profile [ Time Frame: At baseline, Day 1 of each cycle and at study termination ] [ Designated as safety issue: No ]
  • Correlate changes in expression levels of NF-kB lymphocytes in with serum prostate specific antigen levels by serum prostate specific antigen level [ Time Frame: At baseline, Cycle 2 and study termination ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: At baseline, day 1 of each cycle and study termination ] [ Designated as safety issue: No ]

Enrollment: 12
Study Start Date: August 2005
Study Completion Date: September 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
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.
Other Name: oral microencapsulated diindolylmethane

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00305747

Locations
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
Weisberg Cancer Treatment Center
Detroit, Michigan, United States, 48334
Sponsors and Collaborators
Barbara Ann Karmanos Cancer Institute
Investigators
Study Chair: Elisabeth I. Heath, MD Barbara Ann Karmanos Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Elisabeth Heath, Principal Investigator, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier: NCT00305747     History of Changes
Other Study ID Numbers: CDR0000462637, P30CA022453, WSU-D-2979, WSU-0507002581
Study First Received: March 21, 2006
Last Updated: January 14, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Barbara Ann Karmanos Cancer Institute:
recurrent prostate cancer
stage I prostate cancer
stage II prostate cancer
stage III prostate cancer
adenocarcinoma of the prostate
stage IV prostate cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases

ClinicalTrials.gov processed this record on October 16, 2014