Adenocarcinoma of the ProstatePhase 1NCT00450229
Diindolylmethane in Treating Patients Undergoing Surgery for Stage I or Stage II Prostate Cancer
A Phase 1 study testing diindolylmethane, therapeutic conventional surgery and laboratory biomarker analysis in people with Adenocarcinoma of the Prostate and Prostate Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Giving diindolylmethane, a substance found in cruciferous vegetables, may help doctors learn more about how diindolylmethane is used by the body. This randomized phase I trial is studying the side effects and best dose of diindolylmethane compared with a placebo in treating patients undergoing radical prostatectomy… Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Adenocarcinoma of the Prostate, Prostate Cancer, Stage I Prostate Cancer
- What is being tested?
- diindolylmethane, therapeutic conventional surgery and laboratory biomarker analysis
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2007to Feb 2010
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Criteria:
- Histologically confirmed adenocarcinoma of the prostate
- Clinical stage T1 or T2 a, b, or c (stage I-II disease)
- Disease is confined within the prostate gland
- Candidate for radical prostatectomy
- ECOG performance status (PS) 0-1 OR Karnofsky PS 80-100%
- WBC normal
- Platelet count >= 100,000/mm^3
- Hemoglobin >= 10 g/dL
- AST =< 1.5 times upper limit of normal
- Creatinine =< 2.0 mg/dL
- Fertile patients must use effective contraception
- No history of allergic reactions attributed to diindolylmethane (DIM^), any of the inactive ingredients contained in BioResponse-DIM^NG or placebo, or to compounds of similar chemical or biologic composition
- No concurrent uncontrolled illness including, but not limited to, any of the following: Ongoing or active infection, Symptomatic congestive heart failure, Unstable angina pectoris, Cardiac arrhythmia, No psychiatric illness or social situation that would preclude study compliance
- No prior chemotherapy, hormonal therapy, brachytherapy, or external radiotherapy for prostate cancer
- No concurrent nonsteroidal anti-inflammatory drugs, including acetylsalicylic acid, ibuprofen, naproxen sodium, or cyclooxygenase-2 inhibitors
- No concurrent systemic therapy for any other cancer
- No other concurrent investigational agents
- No concurrent p450 inducers or inhibitors, including any of the following: Carbamazepine, Clarithromycin, Fluconazole, Fosphenytoin, Itraconazole, Ketoconazole, Phenobarbital, Phenytoin, Rifabutin, Rifampin
- No concurrent finasteride or dutasteride
- No more than 1 serving of cruciferous vegetables per day for duration of study
- Cruciferous vegetables include the following: broccoli, cauliflower, brussels sprouts, cabbage, arugula, watercress, bok-choy, turnip greens, mustard greens, collard greens, rutabaga, Napa or Chinese cabbage, radishes, turnips, kohlrabi, and kale
- Bilirubin normal
- At least 21 days since prior surgery
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792
About this study
Official title: Phase Ib Placebo-Controlled Trial of Diindolylmethane (BR-DIM) in the Study of the Modulation of Intermediate Endpoint Markers in Patients With Prostate Cancer Who Are Undergoing Prostatectomy
Giving diindolylmethane, a substance found in cruciferous vegetables, may help doctors learn more about how diindolylmethane is used by the body. This randomized phase I trial is studying the side effects and best dose of diindolylmethane compared with a placebo in treating patients undergoing radical prostatectomy for stage I or stage II prostate cancer.
Read the detailed description
PRIMARY OBJECTIVES:
- Compare neoadjuvant prostatic diindolylmethane (DIM^) concentrations in patients with stage I or II adenocarcinoma of the prostate treated with DIM vs placebo prior to radical prostatectomy.
SECONDARY OBJECTIVES:
- Compare the ratio of urinary 2-hydroxyestrone:16-hydroxyestrone in patients treated with these regimens.
II. Compare plasma levels of total prostate-specific antigen (PSA) in patients treated with these regimens.
III. Compare serum testosterone levels in patients treated with these regimens. IV. Compare the ratio of plasma insulin-like growth factor (IGF)-1:IGF binding protein-3 in patients treated with these regimens.
- Compare cytochrome p450 mRNA expression of CYP1A1, CYP1A2, CYP2B1, and CYP3A enzymes in circulating polymorphonuclear leukocytes (PMNs) and in fresh frozen tissue in patients treated with these regimens.
VI. Compare DIM blood steady-state concentrations in patients treated with these regimens.
VII. Identify polymorphisms of CYP1A1, CYP1A2, CYP2B1, and CYP3A in circulating PMNs in patients treated with these regimens.
VIII. Compare tissue levels of PSA, androgen receptor, Ki-67, and caspase 3 in patients treated with these regimens.
OUTLINE:
This is a randomized, placebo-controlled, multicenter study. Patients are randomized to 1 of 3 treatment arms.
Arm I: Patients receive low-dose, nutritional-grade oral diindolylmethane (DIM) twice daily for 21-28 days in the absence of disease progression or unacceptable toxicity. Treatment may continue for up to 60 days, if surgery is delayed.
Arm II: Patients receive high-dose, nutritional-grade oral DIM twice daily as in arm I.
Arm III: Patients receive oral placebo twice daily for 21-28 days in the absence of disease progression or unacceptable toxicity. Treatment may continue for up to 60 days, if surgery is delayed.
Patients in all arms undergo surgical resection of their tumor within 1 day after completion of DIM or placebo.
Patients undergo blood, tissue, and urine sample collection periodically during study for immunohistochemical (IHC)/molecular analyses and pharmacokinetic and pharmacogenomic correlative studies. Patient specimens are assessed for DIM levels in plasma and tissue (by liquid chromatography/mass spectrometry [LC/MS]) and for biologic response to DIM (by TUNEL assay). Intermediate biomarkers of DIM activity are also assessed, including urinary 2-hydroxyestrone:16-hydroxyestrone ratio (by LC/MS assay), plasma total prostate-specific antigen (PSA), plasma insulin-like growth factor (IGF)-1:IGF binding protein-3 ratio (by ELISA), and tissue androgen receptor, PSA, Ki-67, and caspase 3 (by immunohistochemistry). Cytochrome p450 induction and gene expression (CYP1A1, CYP1A2, CYP2B1, CYP3A) are also assessed in tissue and plasma by semiquantitative real-time polymerase chain reaction.
- Conditions
- Adenocarcinoma of the Prostate, Prostate Cancer, Stage I Prostate Cancer, Stage II Prostate Cancer
- Being tested
- diindolylmethane, placebo, therapeutic conventional surgery, laboratory biomarker analysis, pharmacological study
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
diindolylmethaneDrug
Also called DIM
Given PO
placeboDrug
Also called PLCB
Given PO
therapeutic conventional surgeryProcedure or surgery
Undergo surgical resection
laboratory biomarker analysisOther
Correlative studies
Also called pharmacological studies
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | Patients receive low-dose, nutritional-grade oral diindolylmethane (DIM) twice daily for 21-28 days in the absence of disease progression or unacceptable toxicity. Treatment may continue for up to 60 days, if surgery is delayed. Receives: Drug: diindolylmethane; Procedure: therapeutic conventional surgery; Other: laboratory biomarker analysis; Other: pharmacological study |
| Arm II | Experimental | Patients receive high-dose, nutritional-grade oral DIM twice daily as in arm I. Receives: Drug: diindolylmethane; Procedure: therapeutic conventional surgery; Other: laboratory biomarker analysis; Other: pharmacological study |
| Arm III | Placebo comparator | Patients receive oral placebo twice daily for 21-28 days in the absence of disease progression or unacceptable toxicity. Treatment may continue for up to 60 days, if surgery is delayed. Receives: Drug: placebo; Procedure: therapeutic conventional surgery; Other: laboratory biomarker analysis; Other: pharmacological study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tissue levels of DIM
The distribution of levels of DIM will be summarized by treatment arm with descriptive statistics. For the primary comparison between the placebo group and the DIM groups combined, tissue levels of DIM will be compared using Student t-test. In the case of violation of normality assumptions, an appropriate transformation of the data such as logarithm will be considered or a nonparametric test such as Wilcoxon rank-sum test will be used for comparison. A dose-response relation will be explored based on the analysis of covariance (ANCOVA).
Measured: Up to 5 years
Secondary outcomes (7)
Urinary 2-hydroxyestrone/16-hydroxyestrone ratio
Will be summarized by treatment arm with descriptive statistics.
Measured: Up to 5 years
Total PSA
Will be summarized by treatment arm with descriptive statistics.
Measured: Up to 5 years
Serum testosterone
Will be summarized by treatment arm with descriptive statistics.
Measured: Up to 5 years
IGF1:IGFBP-3 ratio
Will be summarized by treatment arm with descriptive statistics.
Measured: Up to 5 years
Tissue measures of messenger RNA of CYPs (CYP1A2, CYP1A1, CYP2B1, CYP3A)
Will be summarized by treatment arm with descriptive statistics.
Measured: Up to 5 years
DIM blood steady-state concentrations
Will be summarized by treatment arm with descriptive statistics.
Measured: Up to 5 years
Measures of androgen receptor, PSA, Ki-67, caspase 3, and TUNEL
Will be summarized by treatment arm with descriptive statistics.
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2007 (estimated)
- Study startFeb 2007
- Primary completionFeb 2010
- Study completionFeb 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Adenocarcinoma of the ProstateStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Jason Gee, Principal investigator, University of Wisconsin, Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00450229
- Sponsor's protocol ID
- NCI-2009-00905
- Other IDs
- CO05816, CDR0000656281, H2006-0255, N01CN35153
- Status last verified
- May 2013
- First submitted
- 20 Mar 2007
- Last updated
- 4 Dec 2015
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib Placebo-Controlled Trial of Diindolylmethane (BR-DIM) in the Study of the Modulation of Intermediate Endpoint Markers in Patients With Prostate Cancer Who Are Undergoing Prostatectomy
- ClinicalTrials.gov ID
- NCT00450229
- Acronym / sponsor ID
- NCI-2009-00905
- Conditions
- Adenocarcinoma of the Prostate, Prostate Cancer, Stage I Prostate Cancer, Stage II Prostate Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Feb 2007
- Primary completion
- Feb 2010 (actual)
- Study completion
- Feb 2010 (actual)
- First posted
- 22 Mar 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Giving diindolylmethane, a substance found in cruciferous vegetables, may help doctors learn more about how diindolylmethane is used by the body. This randomized phase I trial is studying the side effects and best dose of diindolylmethane compared with a placebo in treating patients undergoing radical prostatectomy for stage I or stage II prostate cancer.
Detailed description
PRIMARY OBJECTIVES:
- Compare neoadjuvant prostatic diindolylmethane (DIM^) concentrations in patients with stage I or II adenocarcinoma of the prostate treated with DIM vs placebo prior to radical prostatectomy.
SECONDARY OBJECTIVES:
- Compare the ratio of urinary 2-hydroxyestrone:16-hydroxyestrone in patients treated with these regimens.
II. Compare plasma levels of total prostate-specific antigen (PSA) in patients treated with these regimens.
III. Compare serum testosterone levels in patients treated with these regimens. IV. Compare the ratio of plasma insulin-like growth factor (IGF)-1:IGF binding protein-3 in patients treated with these regimens.
- Compare cytochrome p450 mRNA expression of CYP1A1, CYP1A2, CYP2B1, and CYP3A enzymes in circulating polymorphonuclear leukocytes (PMNs) and in fresh frozen tissue in patients treated with these regimens.
VI. Compare DIM blood steady-state concentrations in patients treated with these regimens.
VII. Identify polymorphisms of CYP1A1, CYP1A2, CYP2B1, and CYP3A in circulating PMNs in patients treated with these regimens.
VIII. Compare tissue levels of PSA, androgen receptor, Ki-67, and caspase 3 in patients treated with these regimens.
OUTLINE:
This is a randomized, placebo-controlled, multicenter study. Patients are randomized to 1 of 3 treatment arms.
Arm I: Patients receive low-dose, nutritional-grade oral diindolylmethane (DIM) twice daily for 21-28 days in the absence of disease progression or unacceptable toxicity. Treatment may continue for up to 60 days, if surgery is delayed.
Arm II: Patients receive high-dose, nutritional-grade oral DIM twice daily as in arm I.
Arm III: Patients receive oral placebo twice daily for 21-28 days in the absence of disease progression or unacceptable toxicity. Treatment may continue for up to 60 days, if surgery is delayed.
Patients in all arms undergo surgical resection of their tumor within 1 day after completion of DIM or placebo.
Patients undergo blood, tissue, and urine sample collection periodically during study for immunohistochemical (IHC)/molecular analyses and pharmacokinetic and pharmacogenomic correlative studies. Patient specimens are assessed for DIM levels in plasma and tissue (by liquid chromatography/mass spectrometry [LC/MS]) and for biologic response to DIM (by TUNEL assay). Intermediate biomarkers of DIM activity are also assessed, including urinary 2-hydroxyestrone:16-hydroxyestrone ratio (by LC/MS assay), plasma total prostate-specific antigen (PSA), plasma insulin-like growth factor (IGF)-1:IGF binding protein-3 ratio (by ELISA), and tissue androgen receptor, PSA, Ki-67, and caspase 3 (by immunohistochemistry). Cytochrome p450 induction and gene expression (CYP1A1, CYP1A2, CYP2B1, CYP3A) are also assessed in tissue and plasma by semiquantitative real-time polymerase chain reaction.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Drug: diindolylmethane, Procedure: therapeutic conventional surgery, Other: laboratory biomarker analysis, Other: pharmacological studyPatients receive low-dose, nutritional-grade oral diindolylmethane (DIM) twice daily for 21-28 days in the absence of disease progression or unacceptable toxicity. Treatment may continue for up to 60 days, if surgery is delayed. |
| Arm II | Experimental | Drug: diindolylmethane, Procedure: therapeutic conventional surgery, Other: laboratory biomarker analysis, Other: pharmacological studyPatients receive high-dose, nutritional-grade oral DIM twice daily as in arm I. |
| Arm III | Placebo comparator | Drug: placebo, Procedure: therapeutic conventional surgery, Other: laboratory biomarker analysis, Other: pharmacological studyPatients receive oral placebo twice daily for 21-28 days in the absence of disease progression or unacceptable toxicity. Treatment may continue for up to 60 days, if surgery is delayed. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| diindolylmethaneAlso: DIMGiven PO | Drug | Arm I, Arm II |
| placeboAlso: PLCBGiven PO | Drug | Arm III |
| therapeutic conventional surgeryUndergo surgical resection | Procedure or surgery | Arm I, Arm II, Arm III |
| laboratory biomarker analysisCorrelative studies | Other | Arm I, Arm II, Arm III |
| pharmacological studyAlso: pharmacological studiesCorrelative studies | Other | Arm I, Arm II, Arm III |
Primary outcome
Tissue levels of DIM
Time frame: Up to 5 years
The distribution of levels of DIM will be summarized by treatment arm with descriptive statistics. For the primary comparison between the placebo group and the DIM groups combined, tissue levels of DIM will be compared using Student t-test. In the case of violation of normality assumptions, an appropriate transformation of the data such as logarithm will be considered or a nonparametric test such as Wilcoxon rank-sum test will be used for comparison. A dose-response relation will be explored based on the analysis of covariance (ANCOVA).
7 secondary outcomes
Urinary 2-hydroxyestrone/16-hydroxyestrone ratio
Time frame: Up to 5 years
Total PSA
Time frame: Up to 5 years
Serum testosterone
Time frame: Up to 5 years
IGF1:IGFBP-3 ratio
Time frame: Up to 5 years
Tissue measures of messenger RNA of CYPs (CYP1A2, CYP1A1, CYP2B1, CYP3A)
Time frame: Up to 5 years
DIM blood steady-state concentrations
Time frame: Up to 5 years
Measures of androgen receptor, PSA, Ki-67, caspase 3, and TUNEL
Time frame: Up to 5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jason Gee principal investigator
University of Wisconsin, Madison
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing diindolylmethane, therapeutic conventional surgery and laboratory biomarker analysis in people with Adenocarcinoma of the Prostate and Prostate Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tissue levels of DIM (time frame: Up to 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2015.