Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Precancerous Conditions

Prostatic Intraepithelial Neoplasia

Carcinoma

Carcinoma in Situ

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Anticoagulants

All Drugs and Chemicals

Bone Density Conservation Agents

Antineoplastic Agents

Other Dietary Supplements

Citric Acid

Sodium Citrate

Toremifene

Antineoplastic Agents, Hormonal

Estrogens

Selective Estrogen Receptor Modulators

Estrogen Receptor Modulators

Hormones

Hormone Antagonists

Citrate

The subject takes one dose by mouth of the 20mg Toremifine Citrate tablet once a day for the length of the trial (360 days).

The subject takes a placebo tablet identical in appearance to the toremifene 20mg tablet, administered by mouth daily for 360 days

Toremifene 20 mg

The subject takes a placebo tablet identical in appearance to the toremifene 20mg tablet, administered by mouth daily for 360 days.

Placebo

Samir Taneja, MD

The purpose of this study is to determine if toremifene citrate is effective and safe in the prevention of prostate cancer in men who have been diagnosed with high grade prostatic intraepithelial neoplasia (PIN).

The purpose of this study is to determine if toremifene citrate is effective and safe in the prevention of prostate cancer in men who have been diagnosed with high grade prostatic intraepithelial neoplasia. Men who have ever been diagnosed with high grade PIN will be enrolled into an 36 month trial and will be assigned to either 20 mg of study drug or placebo per day. Subjects will undergo safety evaluations at Month 3, Month 6, Month 12, Month 18, Month 24, Month 30 and Month 36 along with prostate biopsies at Month 12 and Month 24 and Month 36 to determine efficacy.

Prostate Cancer Prevention Study for Men With High Grade PIN (Prostatic Intraepithelial Neoplasia)

A Randomized, Double-Blind, Placebo-Controlled, Multicenter Efficacy and Safety Study of Toremifene Citrate for the Prevention of Prostate Cancer in Men With High Grade Prostatic Intraepithelial Neoplasia (PIN)

To measure the efficacy of toremifene citrate in men with high grade prostatic intraepithelial neoplasia (PIN). Prostate cancer-free survival distributions (Kaplan-Meier)

To measure the occurrence of a positive cancer biopsy

Measure lipid levels including total cholesterol, LDL, HDL and Triglycerides % change from baseline

% Change from baseline hormone levels, including total testosterone, free testosterone, dihydrotestosterone (DHT) and estradiol

To assess the effect of toremifene in the total PSA (prostate specific antigen) levels from baseline

To assess the effect of toremifene on the AUA (American Urological Association) symptom score mean change from baseline. Scores of 0-7=mild severity, 8-9, moderate, and 20-30, severe with possible responses of 0 (not at all) 1 (\<1/5), 2 (\<50% time), 3 (about 50% time), 4 (\> 50% time) \& 5 (Almost Always). There are 7 questions (1)Incomplete emptying (2)Frequency (3)Intermittency (4)Urgency (5)Weak-stream (6)Straining \& (7)Nocturia. Analysis is change from baseline at final evaluation (36 months) for quality of life due to urinary symptoms. The P Value is from a Wilcoxon signed-rank test. Scores can range from 0-35, highest representing worse symptoms

To measure the occurrence of high grade PIN at the 12, 24, 36 Month intervals in the 360 days study.

To assess the effect of toremifene in % free serum PSA (prostate specific antigen) levels, change from baseline

Toremifene 20mg

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Canada

Argentina

Region of Enrollment

Senior Director, Clinical Operations

MITT: Randomized subjects who were given study drug and did not return it unused and had a baseline and on-study prostate biopsy

Efficacy of Toremifene in the Prevention of Prostate Cancer in Men With High Grade Prostatic Intraepithelial Neoplasia (PIN)

Cholesterol

Triglycerides

All randomized subjects who take at least 1 dose of study drug

The Effect of Toremifene on Lipid Levels

Estradiol

Testosterone total

Testosterone free

Any randomized subject taking at least 1 dose of study drug

The Effect of Toremifene on Hormone Levels

The Effect of Toremifene on Total PSA (Prostate Specific Antigen) Levels

Reference to J Urol.1992 Nov;148(5):1549-57; discussion 1564. AUA symptom index for benign prostatic hyperplasia. The Measurement Committee of the American Urological Assocciation.

The Effect of Toremifene on the Mean Change at 36 Months in AUA (American Urological Association) Symptom Score

Determine occurrence of positive cancer biopsy

Determine occurrence of positive cancer biopsy and survival time

20 mg. Toremifene

Modified, intend-to-treat (MITT) all randomized subj. who take at least 1 dose of study drug, and had baseline and on-study prostate biopsies, where the baseline biopsy did not have cancer.

Occurrence of a Positive Cancer Biopsy

12 months

24 months

36 months

All randomized subjects that took 1 dose of study drug

Occurrence of High Grade PIN at the 12, 24, 36 Month Biopsies

The Effect of Toremifene on % Free Serum PSA (Prostate Specific Antigen) Levels, Change From Baseline

Overall Study

Urogenital Diseases

Male Urogenital Diseases

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Prostatic Diseases

Anti-Inflammatory Agents

Lycopene

Antioxidants

Protective Agents

Radiation-Protective Agents

Lycopene 30mg

Peter H Gann, MD, ScD

The purpose of this research study is to compare the effects of a lycopene supplement made from tomatoes to a placebo (a capsule with no active ingredients) in men who have abnormal cells in the prostate, but have not yet had cancer detected. This study will allow us to see if taking lycopene for six months leads to favorable changes in abnormal prostate tissue and in chemicals measured in the blood that go along with a higher risk of developing cancer.

The Effects of Lycopene on High Risk Prostatic Tissue

R01 CA90759: The Effects of Lycopene on High Risk Prostatic Tissue

We will use conventional immunohistochemistry and computer-based image analysis to test the hypothesis that the lycopene supplements alter the expression of proteins marking the status of proliferation, differentiation, cell regulation and apoptosis in high-risk tissue.

We will use a computerized image analysis system designed for the chemoprevention setting to test the hypothesis that the antioxidants cause a favorable change in a nuclear morphometry index based on nuclear size, shape and chromatin texture.

National Cancer Institute (NCI)

University of Illinois at Chicago

Professor and Director, Division of Pathology Research

Lycopene 30 mg/day until clinically-indicated repeat biopsy performed (approximately 6 months)

Placebo taken until clinically-indicated repeat biopsy performed (approximately 6 months)

Race (NIH/OMB)

Dr. Peter Gann

Tissue Biomarkers

Changes in Serum Biomarkers

Changes in Nuclear Morphometry

Lycopene 30 mg/day until clinically-indicated repeat biopsy performed (approximately 6 months)

Lycopene 30 mg or Placebo: Taken until clinically-indicated repeat biopsy performed (approximately 6 months)

Placebo taken until clinically-indicated repeat biopsy performed (approximately 6 months)

Lycopene 30 mg or Placebo: Taken until clinically-indicated repeat biopsy performed (approximately 6 months)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Prostate Cancer Prevention Study for Men With High Grade PIN (Prostatic Intraepithelial Neoplasia)	NCT00106691	Preneoplastic C... Prostatic Intra...	Toremifene 20 m... Placebo	30 Years -	GTx
Prostate Cancer Prevention Study for Men With High Grade PIN (Prostatic Intraepithelial Neoplasia)	NCT00106691	Preneoplastic C... Prostatic Intra...	Toremifene 20 m... Placebo	30 Years -	GTx
The Effects of Lycopene on High Risk Prostatic Tissue	NCT01443026	Intraepithelial... Prostatic Neopl...	Lycopene 30mg Placebo	40 Years -	University of Illinois at Chicago
The Effects of Lycopene on High Risk Prostatic Tissue	NCT01443026	Intraepithelial... Prostatic Neopl...	Lycopene 30mg Placebo	40 Years -	University of Illinois at Chicago

Spots Global Cancer Trial Database for intraepithelial prostatic neoplasia