Lycopene in Treating Patients Undergoing Radical Prostatectomy for Prostate Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00450749
• Collaborator: (none)
• Enrollment: 10
• Location: 1
• Arms: 3
• Duration (Months): 26.9
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Adenocarcinoma of the Prostate; Stage I Prostate Cancer; Stage II Prostate Cancer; Stage III Prostate Cancer	Other: placebo; Procedure: therapeutic conventional surgery; Other: laboratory biomarker analysis; Drug: lycopene	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Compare the differences in tissue concentrations of lycopene in patients with prostate cancer undergoing radical prostatectomy treated with different doses of neoadjuvant lycopene supplementation.

2. Compare the change in serum lycopene concentration from baseline and at 4-7 weeks in patients treated with different doses of lycopene.

SECONDARY OBJECTIVES:

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Phase II Placebo Controlled Trial of Preoperative Lycopene Supplementation in Prostate Cancer Patients
• Study Start Date: Feb 1, 2008
• Actual Primary Completion Date: May 1, 2010
• Actual Study Completion Date: May 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Arm I (placebo) Patients receive placebo PO QD for 4-7 weeks, and then undergo radical prostatectomy.	Other: placebo; Given PO; Other Names: PLCB ; Procedure: therapeutic conventional surgery; Undergo radical prostatectomy; Other: laboratory biomarker analysis; Correlative studies
Experimental: Arm II (low-dose lycopene) Patients receive low-dose lycopene PO QD for 4-7 weeks, and then undergo radical prostatectomy.	Procedure: therapeutic conventional surgery; Undergo radical prostatectomy; Other: laboratory biomarker analysis; Correlative studies; Drug: lycopene; Given PO; Other Names: all-trans-Lycopene Lyc-O-Mato LYCO psi,psi-Carotene
Experimental: Arm III (high-dose lycopene) Patients receive high-dose lycopene PO QD for 4-7 weeks, and then undergo radical prostatectomy.	Procedure: therapeutic conventional surgery; Undergo radical prostatectomy; Other: laboratory biomarker analysis; Correlative studies; Drug: lycopene; Given PO; Other Names: all-trans-Lycopene Lyc-O-Mato LYCO psi,psi-Carotene

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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 Outcome Measures

1. Ratio of T:DHT in Prostatic Surgical Tissue [At 4-7 weeks]

2. Serum Concentrations of Total Prostate-specific Antigen (PSA), Free PSA, and Human Kallikrein 2 [Baseline and at 4-7 weeks]

3. Growth Potential Assessed by the Ratio of Proliferation (Ki-67):Apoptosis (TUNEL) in Prostatic Surgical Tissue [At 4-7 weeks]

4. Serum Concentrations of Insulin-like Growth Factor (IGF)-1 and IGF Binding Protein-3 [At baseline and at 4-7 weeks]

5. Lymphocyte Oxidative DNA Damage Capacity as Measured by Comet Assay [At baseline and at 4-7 weeks]

6. Expression of GST-pi in Prostatic Surgical Tissue [At 4-7 weeks]

7. Histological Characteristics of Prostatic Surgical Tissue [At 4-7 weeks]

8. Modulation of Expression of Androgen-related Genes as Measured by Microarray in Prostatic Surgical Tissue [At 4-7 weeks]

9. Ratio of Testosterone (T) to Dihydrotestosterone (DHT) in Serum [Baseline and at 4-7 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	M D Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: James Eastham, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00450749
• Other Study ID Numbers: NCI-2009-00857; NCI-2009-00857; MSKCC-06118; MDA-CC-2006-0388; CDR0000653464; CDR0000532938; 06-118; 2006-0388; MDA04-3-01; P30CA016672; N01CN35159
• First Posted: Mar 22, 2007
• Last Update Posted: Dec 18, 2019
• Last Verified: Dec 1, 2019

• Additional relevant MeSH terms: Prostatic Neoplasms; Lycopene

Study Results

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 Detail	There were eleven participants registered, one participant was excluded from the trial before assignment to groups making only ten randomized.

Arm/Group Title	Arm I Placebo	Arm II Low Dose Lycopene	Arm III High-Dose Lycopene
Arm/Group Description	Placebo once daily for 4-7 weeks.	30 mg/day oral Lycopene for 4-7 weeks.	60 mg/day oral Lycopene for 4-7 weeks.
Period Title: Overall Study
STARTED	3	3	4
COMPLETED	3	2	2
NOT COMPLETED	0	1	2

Baseline Characteristics

Arm/Group Title	Arm I Placebo	Arm II Low Dose Lycopene	Arm III High-Dose Lycopene	Total
Arm/Group Description	Placebo once daily for 4-7 weeks.	30 mg/day oral Lycopene for 4-7 weeks.	60 mg/day oral Lycopene for 4-7 weeks.	Total of all reporting groups
Overall Participants	3	3	4	10
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	71	56	66	66.5
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%
Male	3 100%	3 100%	4 100%	10 100%
Region of Enrollment (participants) [Number]
United States	3 100%	3 100%	4 100%	10 100%

Outcome Measures

1. Primary Outcome

Title	Concentration of Lycopene in Prostatic Surgical Tissue
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.
Time Frame	At 4-7 weeks

Outcome Measure Data

Analysis Population Description

Tissue samples collected from five participants for measurement of lycopene levels, representing only 50% (5 of 10) of the participants' enrolled on-trial.

Arm/Group Title	Arm I Placebo	Arm II Low Dose Lycopene	Arm III High-Dose Lycopene
Arm/Group Description	Placebo once daily for 4-7 weeks.	30 mg/day oral Lycopene for 4-7 weeks.	60 mg/day oral Lycopene for 4-7 weeks.
Measure Participants	2	2	2
Sample 1	0.663	0.378	0.723
Sample 2	0.165	0.749	NA

2. Primary Outcome

Title	Serum Levels (ug/dL) of Total Lycopene at Baseline and During Treatment by Group
Description	Serum levels (ug/dL) of total lycopene at baseline and during treatment by group were measured.
Time Frame	Baseline and weeks 4 and 7

Outcome Measure Data

Analysis Population Description

10 participants were analyzed at Baseline versus 8 at Week 4 and versus 5 at Week 7 due to drop out rate.

Arm/Group Title	Arm I Placebo	Arm II Low Dose Lycopene	Arm III High-Dose Lycopene
Arm/Group Description	Placebo once daily for 4-7 weeks.	30 mg/day oral Lycopene for 4-7 weeks.	60 mg/day oral Lycopene for 4-7 weeks.
Measure Participants	3	3	4
Baseline	25.3	32.0	22.7
Week4	98.7	40.4	61.5
Week 7	125.8	52.8	44.4

3. Secondary Outcome

Title	Ratio of T:DHT in Prostatic Surgical Tissue
Time Frame	At 4-7 weeks

Outcome Measure Data

Analysis Population Description

Because the trial closed before the accrual goals were met, therefore only the primary measures were analyzed. No secondary analyses were done.

Arm/Group Title	Arm I Placebo	Arm II Low Dose Lycopene	Arm III High-Dose Lycopene
Arm/Group Description	Placebo once daily for 4-7 weeks.	30 mg/day oral Lycopene for 4-7 weeks.	60 mg/day oral Lycopene for 4-7 weeks.
Measure Participants	0	0	0

4. Secondary Outcome

Title	Serum Concentrations of Total Prostate-specific Antigen (PSA), Free PSA, and Human Kallikrein 2
Time Frame	Baseline and at 4-7 weeks

Outcome Measure Data

Analysis Population Description

Because the trial closed before the accrual goals were met, therefore only the primary measures were analyzed. No secondary analyses were done.

Arm/Group Title	Arm I Placebo	Arm II Low Dose Lycopene	Arm III High-Dose Lycopene
Arm/Group Description	Placebo once daily for 4-7 weeks.	30 mg/day oral Lycopene for 4-7 weeks.	60 mg/day oral Lycopene for 4-7 weeks.
Measure Participants	0	0	0

5. Secondary Outcome

Title	Growth Potential Assessed by the Ratio of Proliferation (Ki-67):Apoptosis (TUNEL) in Prostatic Surgical Tissue
Time Frame	At 4-7 weeks

Outcome Measure Data

Analysis Population Description

Because the trial closed before the accrual goals were met, therefore only the primary measures were analyzed. No secondary analyses were done.

Arm/Group Title	Arm I Placebo	Arm II Low Dose Lycopene	Arm III High-Dose Lycopene
Arm/Group Description	Placebo once daily for 4-7 weeks.	30 mg/day oral Lycopene for 4-7 weeks.	60 mg/day oral Lycopene for 4-7 weeks.
Measure Participants	0	0	0

6. Secondary Outcome

Title	Serum Concentrations of Insulin-like Growth Factor (IGF)-1 and IGF Binding Protein-3
Time Frame	At baseline and at 4-7 weeks

Outcome Measure Data

Analysis Population Description

Because the trial closed before the accrual goals were met, therefore only the primary measures were analyzed. No secondary analyses were done.

Arm/Group Title	Arm I Placebo	Arm II Low Dose Lycopene	Arm III High-Dose Lycopene
Arm/Group Description	Placebo once daily for 4-7 weeks.	30 mg/day oral Lycopene for 4-7 weeks.	60 mg/day oral Lycopene for 4-7 weeks.
Measure Participants	0	0	0

7. Secondary Outcome

Title	Lymphocyte Oxidative DNA Damage Capacity as Measured by Comet Assay
Time Frame	At baseline and at 4-7 weeks

Outcome Measure Data

Analysis Population Description

Because the trial closed before the accrual goals were met, therefore only the primary measures were analyzed. No secondary analyses were done.

Arm/Group Title	Arm I Placebo	Arm II Low Dose Lycopene	Arm III High-Dose Lycopene
Arm/Group Description	Placebo once daily for 4-7 weeks.	30 mg/day oral Lycopene for 4-7 weeks.	60 mg/day oral Lycopene for 4-7 weeks.
Measure Participants	0	0	0

8. Secondary Outcome

Title	Expression of GST-pi in Prostatic Surgical Tissue
Time Frame	At 4-7 weeks

Outcome Measure Data

Analysis Population Description

Because the trial closed before the accrual goals were met, therefore only the primary measures were analyzed. No secondary analyses were done.

Arm/Group Title	Arm I Placebo	Arm II Low Dose Lycopene	Arm III High-Dose Lycopene
Arm/Group Description	Placebo once daily for 4-7 weeks.	30 mg/day oral Lycopene for 4-7 weeks.	60 mg/day oral Lycopene for 4-7 weeks.
Measure Participants	0	0	0

9. Secondary Outcome

Title	Histological Characteristics of Prostatic Surgical Tissue
Time Frame	At 4-7 weeks

Outcome Measure Data

Analysis Population Description

Because the trial closed before the accrual goals were met, therefore only the primary measures were analyzed. No secondary analyses were done.

Arm/Group Title	Arm I Placebo	Arm II Low Dose Lycopene	Arm III High-Dose Lycopene
Arm/Group Description	Placebo once daily for 4-7 weeks.	30 mg/day oral Lycopene for 4-7 weeks.	60 mg/day oral Lycopene for 4-7 weeks.
Measure Participants	0	0	0

10. Secondary Outcome

Title	Modulation of Expression of Androgen-related Genes as Measured by Microarray in Prostatic Surgical Tissue
Time Frame	At 4-7 weeks

Outcome Measure Data

Analysis Population Description

Because the trial closed before the accrual goals were met, therefore only the primary measures were analyzed. No secondary analyses were done.

Arm/Group Title	Arm I Placebo	Arm II Low Dose Lycopene	Arm III High-Dose Lycopene
Arm/Group Description	Placebo once daily for 4-7 weeks.	30 mg/day oral Lycopene for 4-7 weeks.	60 mg/day oral Lycopene for 4-7 weeks.
Measure Participants	0	0	0

11. Secondary Outcome

Title	Ratio of Testosterone (T) to Dihydrotestosterone (DHT) in Serum
Time Frame	Baseline and at 4-7 weeks

Outcome Measure Data

Analysis Population Description

Because the trial closed before the accrual goals were met, therefore only the primary measures were analyzed. No secondary analyses were done.

Arm/Group Title	Arm I Placebo	Arm II Low Dose Lycopene	Arm III High-Dose Lycopene
Arm/Group Description	Placebo once daily for 4-7 weeks.	30 mg/day oral Lycopene for 4-7 weeks.	60 mg/day oral Lycopene for 4-7 weeks.
Measure Participants	0	0	0

Adverse Events

Time Frame	13 months
Arm/Group Title	Arm I Placebo		Arm II Low Dose Lycopene		Arm III High-Dose Lycopene
Arm/Group Description	Placebo once daily for 4-7 weeks.		30 mg/day oral Lycopene for 4-7 weeks.		60 mg/day oral Lycopene for 4-7 weeks.
All Cause Mortality
	Arm I Placebo		Arm II Low Dose Lycopene		Arm III High-Dose Lycopene
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I Placebo		Arm II Low Dose Lycopene		Arm III High-Dose Lycopene
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	Arm I Placebo		Arm II Low Dose Lycopene		Arm III High-Dose Lycopene
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)		3/4 (75%)
Cardiac disorders
Cardia Arrythmia	0/3 (0%)	0	0/3 (0%)	0	1/4 (25%)	1
Sinus Bradycardia	0/3 (0%)	0	0/3 (0%)	0	1/4 (25%)	1
General disorders
Dizziness	0/3 (0%)	0	0/3 (0%)	0	1/4 (25%)	1
Insomnia	0/3 (0%)	0	0/3 (0%)	0	1/4 (25%)	1
Anxiety	0/3 (0%)	0	0/3 (0%)	0	1/4 (25%)	1
Depression	0/3 (0%)	0	0/3 (0%)	0	1/4 (25%)	1
Renal and urinary disorders
Urinary frequency	0/3 (0%)	0	0/3 (0%)	0	1/4 (25%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	0/3 (0%)	0	0/3 (0%)	0	1/4 (25%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.