Lycopene in Treating Patients Undergoing Radical Prostatectomy for Prostate Cancer

Adenocarcinoma of the Prostate Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00450749
• Other study ID #: NCI-2009-00857
• Secondary ID: NCI-2009-00857MS
• Status: Completed
• Phase: Phase 2
• Start date: February 2008
• Est. completion date: May 2010

Study information

• Verified date: December 2019
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: May 2010
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Prostate
• Prostatic Neoplasms
• Stage I Prostate Cancer
• Stage II Prostate Cancer
• Stage III Prostate Cancer

Intervention

Other:
• placebo
Given PO

Procedure:
• therapeutic conventional surgery
Undergo radical prostatectomy

Other:
• laboratory biomarker analysis
Correlative studies

Drug:
• lycopene
Given PO

Locations

Country	Name	City	State
United States	M D Anderson Cancer Center	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

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