Phase II Placebo Controlled Trial of Preoperative Lycopene Supplementation in Prostate Cancer Patients
18 Years
N/A
Male
Adenocarcinoma of the Prostate, Stage I Prostate Cancer, Stage II Prostate Cancer, Stage III Prostate Cancer
Trial Information
Phase II Placebo Controlled Trial of Preoperative Lycopene Supplementation in Prostate Cancer Patients
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.
Inclusion 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)
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Outcome Measure:
Concentration of Lycopene in Prostatic Surgical Tissue
Outcome Description:
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.
Outcome Time Frame:
At 4-7 weeks
Safety Issue:
No
Principal Investigator
James Eastham
Investigator Role:
Principal Investigator
Investigator Affiliation:
M.D. Anderson Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2009-00857
NCT ID:
NCT00450749
Start Date:
February 2008
Completion Date:
Related Keywords:
- Adenocarcinoma of the Prostate
- Stage I Prostate Cancer
- Stage II Prostate Cancer
- Stage III Prostate Cancer
- Adenocarcinoma
- Adenocarcinoma, Mucinous
- Prostatic Neoplasms
Name | Location |
|---|---|
| M D Anderson Cancer Center | Houston, Texas 77030 |
