Lycopene in Treating Patients Undergoing Radical Prostatectomy for Prostate Cancer

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase II Placebo Controlled Trial of Preoperative Lycopene Supplementation in Prostate Cancer Patients

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

Intervention / Treatment
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* Other: placebo
* Procedure: therapeutic conventional surgery
* Other: laboratory biomarker analysis
* Drug: lycopene


Participation Criteria
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Eligibility Criteria
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Criteria: Creatinine normal Biopsy-confirmed adenocarcinoma of the prostate Localized disease Planned radical prostatectomy ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100% WBC >= 3,000/mm^3 Platelet count >= 100,000/mm^3 Bilirubin normal AST and ALT =< 2.5 times upper limit of normal Fertile patients must use effective barrier contraception No other invasive cancer (except nonmelanoma skin cancer) within the past 2 years Patients who received curative treatment and have shown no evidence of recurrence within the past 2 years are eligible No history of allergic reactions attributed to compounds of similar chemical or biological composition to lycopene (e.g., other carotenoids, including lutein and beta-carotene) More than 30 days since prior regular (> once weekly) lycopene supplementation (>= 15 mg/day) and meets the following criteria: no more than 2 servings of tomato sauce, juice, or soup per week; no more than 4 servings of grapefruit, raw tomato, or watermelon per week Must not consume 1 serving of tomato sauce, juice, or soup per week AND more than 2 servings of grapefruit, raw tomato, or watermelon per week More than 30 days since prior and no concurrent investigational medication No concurrent chemotherapy, radiotherapy, hormonal therapy, or immunotherapy No history of allergy to foods containing lycopene (e.g., tomatoes or tomato products, watermelon, guava, and pink grapefruit) 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; psychiatric illness/social situations that would limit compliance with study requirements No prior therapy for prostate cancer, including radiotherapy to the prostate or pelvis, androgen ablation, or antiandrogen systemic therapy No other concurrent lycopene (>= 15 mg/day)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Arm I (placebo)<br>Patients receive placebo PO QD for 4-7 weeks, and then undergo radical prostatectomy. | Other: placebo<br>* Given PO<br>* Other names: PLCB;Procedure: therapeutic conventional surgery<br>* Undergo radical prostatectomy<br>Other: laboratory biomarker analysis<br>* Correlative studies<br>|
| Experimental: Arm II (low-dose lycopene)<br>Patients receive low-dose lycopene PO QD for 4-7 weeks, and then undergo radical prostatectomy. | Procedure: therapeutic conventional surgery<br>* Undergo radical prostatectomy<br>Other: laboratory biomarker analysis<br>* Correlative studies<br>Drug: lycopene<br>* Given PO<br>* Other names: psi,psi-Carotene;|
| Experimental: Arm III (high-dose lycopene)<br>Patients receive high-dose lycopene PO QD for 4-7 weeks, and then undergo radical prostatectomy. | Procedure: therapeutic conventional surgery<br>* Undergo radical prostatectomy<br>Other: laboratory biomarker analysis<br>* Correlative studies<br>Drug: lycopene<br>* Given PO<br>* Other names: psi,psi-Carotene;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of Lycopene in Prostatic Surgical Tissue | 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. | At 4-7 weeks | 
| Serum Levels (ug/dL) of Total Lycopene at Baseline and During Treatment by Group | Serum levels (ug/dL) of total lycopene at baseline and during treatment by group were measured. | Baseline and weeks 4 and 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |