Lycopene in Treating Patients Undergoing Radical Prostatectomy for Prostate Cancer

Phase 2

Completed

Conditions: Adenocarcinoma of the Prostate
Stage I Prostate Cancer
Stage II Prostate Cancer
Stage III Prostate Cancer

Interventions: Other: placebo
Procedure: therapeutic conventional surgery
Other: laboratory biomarker analysis
Drug: lycopene

Registration Number: NCT00450749

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: This randomized phase II trial studies how well different doses of lycopene work in treating patients undergoing radical prostatectomy for prostate cancer. The use of lycopene, a substance found in tomatoes, may keep prostate cancer from growing or coming back after surgery.

Detailed Description: PRIMARY OBJECTIVES:

I. Compare the differences in tissue concentrations of lycopene in patients with prostate cancer undergoing radical prostatectomy treated with different doses of neoadjuvant lycopene supplementation.

II. Compare the change in serum lycopene concentration from baseline and at 4-7 weeks in patients treated with different doses of lycopene.

SECONDARY OBJECTIVES:

I. Determine the effect of this treatment in down-regulating 5-alpha-reductase activity by measuring the change in the ratio of testosterone (T) to dihydrotestosterone (DHT) in serum at baseline and at 4-7 weeks and the ratio of T:DHT in prostatic surgical tissue post-treatment.

II. Determine the effect of this treatment in attenuating baseline blood serum concentrations of total prostate-specific antigen (PSA), free PSA, and human kallikrein 2 in these patients.

III. Determine the effect of this treatment on growth potential by examining post-treatment radical prostatectomy tissue specimens for proliferative index (PI) by Ki-67 expression, apoptotic index (AI) by TUNEL assay, and PI:AI ratio in these patients.

IV. Determine the effect of this treatment in modulating putative biomarkers of lycopene efficacy, including serum concentrations of insulin-like growth factor (IGF)-1 and IGF binding protein-3, lymphocyte oxidative DNA damage capacity by Comet assay, and GST-pi expression in prostatic tissue from these patients.

V. Compare the histological effect of different doses of lycopene on putative prognostic features, including the presence and extent of high-grade prostatic intraepithelial neoplasia, prostatitis, total tumor volume, local invasion (vascular and lymphatic, capsular, seminal vesicle), pathologic stage, Gleason score, surgical margins, and lymph node status in these patients.

VI. Determine the effect of this treatment in modulating the RNA expression of androgen-related genes by microarray analysis in these patients.

OUTLINE:

This is a randomized, placebo-controlled, double-blind, multicenter study. Patients are stratified according to participating center. Patients are randomized to 1 of 3 treatment arms.

ARM I: Patients receive placebo orally (PO) once daily (QD) for 4-7 weeks, and then undergo radical prostatectomy.

ARM II: Patients receive low-dose lycopene PO QD for 4-7 weeks, and then undergo radical prostatectomy.

ARM III: Patients receive high-dose lycopene PO QD for 4-7 weeks, and then undergo radical prostatectomy.

Tumor samples are collected from prostatectomy for laboratory studies, including GST-pi expression by immunohistochemistry; histological analysis; microarray analysis of androgen-related genes; ratio of testosterone (T) to dihydrotestosterone (DHT); Ki-67 expression; and lycopene tumor-concentration measurement.

Patients undergo blood collection at baseline, week 4, and week 7 for laboratory studies, including serum lycopene concentration measurement; level of T or DHT by high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) analysis; serum concentrations of total prostate-specific antigen (PSA), free PSA, and human kallikrein 2; lymphocyte oxidative DNA damage capacity; and serum concentrations of insulin-like growth factor (IGF)-1 and IGF binding protein-3 by radioimmunological assay.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 10

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (placebo)	laboratory biomarker analysis	Patients receive placebo PO QD for 4-7 weeks, and then undergo radical prostatectomy.
Arm I (placebo)	placebo	Patients receive placebo PO QD for 4-7 weeks, and then undergo radical prostatectomy.
Arm I (placebo)	therapeutic conventional surgery	Patients receive placebo PO QD for 4-7 weeks, and then undergo radical prostatectomy.
Arm II (low-dose lycopene)	therapeutic conventional surgery	Patients receive low-dose lycopene PO QD for 4-7 weeks, and then undergo radical prostatectomy.
Arm II (low-dose lycopene)	lycopene	Patients receive low-dose lycopene PO QD for 4-7 weeks, and then undergo radical prostatectomy.
Arm III (high-dose lycopene)	therapeutic conventional surgery	Patients receive high-dose lycopene PO QD for 4-7 weeks, and then undergo radical prostatectomy.
Arm II (low-dose lycopene)	laboratory biomarker analysis	Patients receive low-dose lycopene PO QD for 4-7 weeks, and then undergo radical prostatectomy.
Arm III (high-dose lycopene)	laboratory biomarker analysis	Patients receive high-dose lycopene PO QD for 4-7 weeks, and then undergo radical prostatectomy.
Arm III (high-dose lycopene)	lycopene	Patients receive high-dose lycopene PO QD for 4-7 weeks, and then undergo radical prostatectomy.

Primary Outcome Measures

Name	Time	Method
Concentration of Lycopene in Prostatic Surgical Tissue	At 4-7 weeks	Total tissue lycopene concentrations in radical prostatectomy specimens in participants receiving 6 weeks (± 1 week) of preoperative supplementation with 60 mg/day lycopene, 30 mg/day lycopene, or placebo. Concentration of lycopene in prostatic surgical tissue calculated using the high-performance liquid chromatography (HPLC) method.
Serum Levels (ug/dL) of Total Lycopene at Baseline and During Treatment by Group	Baseline and weeks 4 and 7	Serum levels (ug/dL) of total lycopene at baseline and during treatment by group were measured.

Secondary Outcome Measures

Name	Time	Method
Ratio of T:DHT in Prostatic Surgical Tissue	At 4-7 weeks
Serum Concentrations of Total Prostate-specific Antigen (PSA), Free PSA, and Human Kallikrein 2	Baseline and at 4-7 weeks
Growth Potential Assessed by the Ratio of Proliferation (Ki-67):Apoptosis (TUNEL) in Prostatic Surgical Tissue	At 4-7 weeks
Serum Concentrations of Insulin-like Growth Factor (IGF)-1 and IGF Binding Protein-3	At baseline and at 4-7 weeks
Lymphocyte Oxidative DNA Damage Capacity as Measured by Comet Assay	At baseline and at 4-7 weeks
Expression of GST-pi in Prostatic Surgical Tissue	At 4-7 weeks
Histological Characteristics of Prostatic Surgical Tissue	At 4-7 weeks
Modulation of Expression of Androgen-related Genes as Measured by Microarray in Prostatic Surgical Tissue	At 4-7 weeks
Ratio of Testosterone (T) to Dihydrotestosterone (DHT) in Serum	Baseline and at 4-7 weeks