Clinical trial NCT00450749: Lycopene in Treating Patients Undergoing Radical Prostatectomy for Prostate Cancer
Official title: Phase II Placebo Controlled Trial of Preoperative Lycopene Supplementation in Prostate Cancer Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adenocarcinoma of the Prostate
Stage I Prostate Cancer
Stage II Prostate Cancer
Stage III Prostate Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-03-22
Enrollment: 10
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Concentration of Lycopene in Prostatic Surgical Tissue
timeFrame: At 4-7 weeks
measure: Serum Levels (ug/dL) of Total Lycopene at Baseline and During Treatment by Group
timeFrame: Baseline and weeks 4 and 7
Secondary outcomes:
measure: Ratio of T:DHT in Prostatic Surgical Tissue
timeFrame: At 4-7 weeks
measure: Serum Concentrations of Total Prostate-specific Antigen (PSA), Free PSA, and Human Kallikrein 2
timeFrame: Baseline and at 4-7 weeks
measure: Growth Potential Assessed by the Ratio of Proliferation (Ki-67):Apoptosis (TUNEL) in Prostatic Surgical Tissue
timeFrame: At 4-7 weeks
measure: Serum Concentrations of Insulin-like Growth Factor (IGF)-1 and IGF Binding Protein-3
timeFrame: At baseline and at 4-7 weeks
measure: Lymphocyte Oxidative DNA Damage Capacity as Measured by Comet Assay
timeFrame: At baseline and at 4-7 weeks
measure: Expression of GST-pi in Prostatic Surgical Tissue
timeFrame: At 4-7 weeks
measure: Histological Characteristics of Prostatic Surgical Tissue
timeFrame: At 4-7 weeks
measure: Modulation of Expression of Androgen-related Genes as Measured by Microarray in Prostatic Surgical Tissue
timeFrame: At 4-7 weeks
measure: Ratio of Testosterone (T) to Dihydrotestosterone (DHT) in Serum
timeFrame: Baseline and at 4-7 weeks
Other outcomes:
Locations:
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: James Eastham
role: PRINCIPAL_INVESTIGATOR
References: