Ignite Creation Date:
2024-05-05 @ 5:27 PM
Last Modification Date:
2024-10-26 @ 9:31 AM
Study NCT ID:
NCT00450229
Status:
COMPLETED
Last Update Posted:
2015-12-04
First Post:
2007-03-20
Brief Title:
Diindolylmethane in Treating Patients Undergoing Surgery for Stage I or Stage II Prostate Cancer
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
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
Status:
COMPLETED
Status Verified Date:
2013-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 for stage I or stage II prostate cancer
Detailed Description:
PRIMARY OBJECTIVES
I 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
I Compare the ratio of urinary 2-hydroxyestrone16-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-1IGF binding protein-3 in patients treated with these regimens
V 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 IHCmolecular analyses and pharmacokinetic and pharmacogenomic correlative studies Patient specimens are assessed for DIM levels in plasma and tissue by liquid chromatographymass spectrometry LCMS and for biologic response to DIM by TUNEL assay Intermediate biomarkers of DIM activity are also assessed including urinary 2-hydroxyestrone16-hydroxyestrone ratio by LCMS assay plasma total prostate-specific antigen PSA plasma insulin-like growth factor IGF-1IGF 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
I 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
I Compare the ratio of urinary 2-hydroxyestrone16-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-1IGF binding protein-3 in patients treated with these regimens
V 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 IHCmolecular analyses and pharmacokinetic and pharmacogenomic correlative studies Patient specimens are assessed for DIM levels in plasma and tissue by liquid chromatographymass spectrometry LCMS and for biologic response to DIM by TUNEL assay Intermediate biomarkers of DIM activity are also assessed including urinary 2-hydroxyestrone16-hydroxyestrone ratio by LCMS assay plasma total prostate-specific antigen PSA plasma insulin-like growth factor IGF-1IGF 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| N01CN35153 | NIH | None | httpsreporternihgovquickSearchN01CN35153 |
| CO05816 | None | None | None |
| CDR0000656281 | None | None | None |
| H2006-0255 | None | None | None |