Phase II Placebo Controlled Trial of Preoperative Lycopene Supplementation in Prostate Cancer Patients
I. Compare the differences in tissue concentrations of lycopene in patients with prostate
cancer undergoing radical prostatectomy treated with different doses of neoadjuvant lycopene
II. Compare the change in serum lycopene concentration from baseline and at 4-7 weeks in
patients treated with different doses of lycopene.
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
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
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.
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
ARM I: Patients receive placebo orally (PO) once daily (QD) for 4-7 weeks, and then undergo
ARM II: Patients receive low-dose lycopene PO QD for 4-7 weeks, and then undergo radical
ARM III: Patients receive high-dose lycopene PO QD for 4-7 weeks, and then undergo radical
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.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
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
M.D. Anderson Cancer Center
United States: Food and Drug Administration
|M D Anderson Cancer Center||Houston, Texas 77030|