Lycopene in Treating Patients Undergoing Radical Prostatectomy for Prostate Cancer

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

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.

Study Overview

• Status: Completed
• Conditions: Stage I Prostate Cancer; Stage II Prostate Cancer; Stage III Prostate Cancer; Adenocarcinoma of the Prostate
• Intervention / Treatment: Other: laboratory biomarker analysis; Other: placebo; Procedure: therapeutic conventional surgery; Drug: lycopene

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Arm I (placebo); Patients receive placebo PO QD for 4-7 weeks, and then undergo radical prostatectomy.	Other: laboratory biomarker analysis; Correlative studies; Other: placebo; Given PO; Other Names: PLCB; Procedure: therapeutic conventional surgery; Undergo radical prostatectomy
Experimental: Arm II (low-dose lycopene); Patients receive low-dose lycopene PO QD for 4-7 weeks, and then undergo radical prostatectomy.	Other: laboratory biomarker analysis; Correlative studies; Procedure: therapeutic conventional surgery; Undergo radical prostatectomy; Drug: lycopene; Given PO; Other Names: all-trans-Lycopene; Lyc-O-Mato; LYCO; psi,psi-Carotene
Experimental: Arm III (high-dose lycopene); Patients receive high-dose lycopene PO QD for 4-7 weeks, and then undergo radical prostatectomy.	Other: laboratory biomarker analysis; Correlative studies; Procedure: therapeutic conventional surgery; Undergo radical prostatectomy; Drug: lycopene; Given PO; Other Names: all-trans-Lycopene; Lyc-O-Mato; LYCO; psi,psi-Carotene

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: James Eastham, M.D. Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (Actual): May 1, 2010
• Study Completion (Actual): May 1, 2010

Study Registration Dates

• First Submitted: March 20, 2007
• First Submitted That Met QC Criteria: March 20, 2007
• First Posted (Estimate): March 22, 2007

Study Record Updates

• Last Update Posted (Actual): December 18, 2019
• Last Update Submitted That Met QC Criteria: December 16, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Antineoplastic Agents; Protective Agents; Antioxidants; Anticarcinogenic Agents; Radiation-Protective Agents; Lycopene
• Other Study ID Numbers: NCI-2009-00857 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); P30CA016672 (U.S. NIH Grant/Contract); N01CN35159 (U.S. NIH Grant/Contract); MSKCC-06118; MDA-CC-2006-0388; CDR0000653464; CDR0000532938; 06-118; 2006-0388 (Other Identifier: M D Anderson Cancer Center); MDA04-3-01 (Other Identifier: DCP)