Adenocarcinoma of the Prostate, Stage III Prostate Cancer, Stage II Prostate Cancer, Stage I Prostate Cancer
Conditions
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.
Interventions
OTHERplacebo
Given PO
PROCEDUREtherapeutic conventional surgery
Undergo radical prostatectomy
OTHERlaboratory biomarker analysis
Correlative studies
DRUGlycopene
Given PO
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of Lycopene in Prostatic Surgical Tissue | At 4-7 weeks | 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. |
| Serum Levels (ug/dL) of Total Lycopene at Baseline and During Treatment by Group | Baseline and weeks 4 and 7 | Serum levels (ug/dL) of total lycopene at baseline and during treatment by group were measured. |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Ratio of T:DHT 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 |
| Expression of GST-pi 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 |
Countries
United States
Participant flow
Recruitment details
Recruitment Period: April 11, 2008 to April 15, 2009. All recruitment was done in a medical clinic setting, and all participants enrolled at Memorial Sloan-Kettering Cancer Center.
Pre-assignment details
There were eleven participants registered, one participant was excluded from the trial before assignment to groups making only ten randomized.
Participants by arm
| Arm | Count |
|---|---|
| Arm I Placebo Placebo once daily for 4-7 weeks. | 3 |
| Arm II Low Dose Lycopene 30 mg/day oral Lycopene for 4-7 weeks. | 3 |
| Arm III High-Dose Lycopene 60 mg/day oral Lycopene for 4-7 weeks. | 4 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Noncompliant | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | Arm I Placebo | Arm II Low Dose Lycopene | Arm III High-Dose Lycopene | Total |
|---|---|---|---|---|
| Age, Continuous | 71 years | 56 years | 66 years | 66.5 years |
| Region of Enrollment United States | 3 participants | 3 participants | 4 participants | 10 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 4 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 3 | 0 / 3 | 3 / 4 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 4 |
Outcome results
Primary
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.
Time frame: At 4-7 weeks
Population: Tissue samples collected from five participants for measurement of lycopene levels, representing only 50% (5 of 10) of the participants' enrolled on-trial.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm I Placebo | Concentration of Lycopene in Prostatic Surgical Tissue | Sample 1 | 0.663 ug/dL |
| Arm I Placebo | Concentration of Lycopene in Prostatic Surgical Tissue | Sample 2 | 0.165 ug/dL |
| Arm II Low Dose Lycopene | Concentration of Lycopene in Prostatic Surgical Tissue | Sample 1 | 0.378 ug/dL |
| Arm II Low Dose Lycopene | Concentration of Lycopene in Prostatic Surgical Tissue | Sample 2 | 0.749 ug/dL |
| Arm III High-Dose Lycopene | Concentration of Lycopene in Prostatic Surgical Tissue | Sample 1 | 0.723 ug/dL |
| Arm III High-Dose Lycopene | Concentration of Lycopene in Prostatic Surgical Tissue | Sample 2 | NA ug/dL |
Primary
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.
Time frame: Baseline and weeks 4 and 7
Population: 10 participants were analyzed at Baseline versus 8 at Week 4 and versus 5 at Week 7 due to drop out rate.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Arm I Placebo | Serum Levels (ug/dL) of Total Lycopene at Baseline and During Treatment by Group | Week4 | 98.7 ug/dL |
| Arm I Placebo | Serum Levels (ug/dL) of Total Lycopene at Baseline and During Treatment by Group | Baseline | 25.3 ug/dL |
| Arm I Placebo | Serum Levels (ug/dL) of Total Lycopene at Baseline and During Treatment by Group | Week 7 | 125.8 ug/dL |
| Arm II Low Dose Lycopene | Serum Levels (ug/dL) of Total Lycopene at Baseline and During Treatment by Group | Week4 | 40.4 ug/dL |
| Arm II Low Dose Lycopene | Serum Levels (ug/dL) of Total Lycopene at Baseline and During Treatment by Group | Baseline | 32.0 ug/dL |
| Arm II Low Dose Lycopene | Serum Levels (ug/dL) of Total Lycopene at Baseline and During Treatment by Group | Week 7 | 52.8 ug/dL |
| Arm III High-Dose Lycopene | Serum Levels (ug/dL) of Total Lycopene at Baseline and During Treatment by Group | Baseline | 22.7 ug/dL |
| Arm III High-Dose Lycopene | Serum Levels (ug/dL) of Total Lycopene at Baseline and During Treatment by Group | Week 7 | 44.4 ug/dL |
| Arm III High-Dose Lycopene | Serum Levels (ug/dL) of Total Lycopene at Baseline and During Treatment by Group | Week4 | 61.5 ug/dL |
Secondary
Expression of GST-pi in Prostatic Surgical Tissue
Time frame: At 4-7 weeks
Population: Because the trial closed before the accrual goals were met, therefore only the primary measures were analyzed. No secondary analyses were done.
Secondary
Growth Potential Assessed by the Ratio of Proliferation (Ki-67):Apoptosis (TUNEL) in Prostatic Surgical Tissue
Time frame: At 4-7 weeks
Population: Because the trial closed before the accrual goals were met, therefore only the primary measures were analyzed. No secondary analyses were done.
Secondary
Histological Characteristics of Prostatic Surgical Tissue
Time frame: At 4-7 weeks
Population: Because the trial closed before the accrual goals were met, therefore only the primary measures were analyzed. No secondary analyses were done.
Secondary
Lymphocyte Oxidative DNA Damage Capacity as Measured by Comet Assay
Time frame: At baseline and at 4-7 weeks
Population: Because the trial closed before the accrual goals were met, therefore only the primary measures were analyzed. No secondary analyses were done.
Secondary
Modulation of Expression of Androgen-related Genes as Measured by Microarray in Prostatic Surgical Tissue
Time frame: At 4-7 weeks
Population: Because the trial closed before the accrual goals were met, therefore only the primary measures were analyzed. No secondary analyses were done.
Secondary
Ratio of T:DHT in Prostatic Surgical Tissue
Time frame: At 4-7 weeks
Population: Because the trial closed before the accrual goals were met, therefore only the primary measures were analyzed. No secondary analyses were done.
Secondary
Ratio of Testosterone (T) to Dihydrotestosterone (DHT) in Serum
Time frame: Baseline and at 4-7 weeks
Population: Because the trial closed before the accrual goals were met, therefore only the primary measures were analyzed. No secondary analyses were done.
Secondary
Serum Concentrations of Insulin-like Growth Factor (IGF)-1 and IGF Binding Protein-3
Time frame: At baseline and at 4-7 weeks
Population: Because the trial closed before the accrual goals were met, therefore only the primary measures were analyzed. No secondary analyses were done.
Secondary
Serum Concentrations of Total Prostate-specific Antigen (PSA), Free PSA, and Human Kallikrein 2
Time frame: Baseline and at 4-7 weeks
Population: Because the trial closed before the accrual goals were met, therefore only the primary measures were analyzed. No secondary analyses were done.