Phase I Multiple Dose Pharmacokinetic Study of Lycopene Delivered in a Well-Defined Food-Based Lycopene Delivery System (Tomato Paste-Oil Mixture) in Patients at Increased Risk for Developing Prostate Cancer
- Define the toxicity and safety of lycopene administered as a food-based delivery system
as a chemoprevention agent in patients who are at a high risk of developing prostate
- Define the pharmacokinetics and tissue distribution in patients receiving this regimen.
- Characterize surrogate endpoint biomarkers (SEBs) in the peripheral blood, buccal
mucosa, and the prostate itself, which will provide evidence of biological activity
relevant to a chemoprevention effect.
- Characterize the oxidative stress state of the individual by studies of DNA
oxidation in the prostate and buccal mucosa, as well as DNA oxidation and lipid
peroxidation within the peripheral blood.
- Define the effects of lycopene through a food delivery system on prostate
histology (prostatic intraepithelial neoplasia), markers of cellular proliferation
[PCNA], and apoptosis in the prostate.
- Evaluate the effects of lycopene on the serum levels of total prostate-specific
antigen (PSA), free PSA, and PSA density.
- Provide the basic knowledge in reference to toxicity, pharmacokinetics, and SEBs needed
to proceed to a large phase II or III lycopene study in these patients.
OUTLINE: This is a dose-escalation, multicenter study.
Patients receive oral lycopene in tomato paste and olive oil, once, twice, or three times
daily for 3 months.
Cohorts of 6 patients receive escalating doses of lycopene until the maximum tolerated dose
(MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients
experience dose-limiting toxicity.
Patients undergo buccal scrapings and blood collection periodically during study for
pharmacokinetics and biomarker studies.
After completion of study treatment, patients are followed for 1 month.
PROJECTED ACCRUAL: A total of 18 patients will be accrued for this study.
Primary Purpose: Prevention
Toxicity as measured by NCI CTC v2.0
Keith A. Rodvold
University of Illinois
United States: Federal Government