Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Symptoms and General Pathology

Carcinoma

Breast Neoplasms

Carcinoma, Ductal

Hyperplasia

Carcinoma in Situ

Carcinoma, Intraductal, Noninfiltrating

Precancerous Conditions

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Breast Carcinoma In Situ

Central Nervous System Depressants

All Drugs and Chemicals

Anesthetics

Nipple aspirator, ductal lavage microcatheter, blood draw

The subject will undergo nipple aspiration with a suction device designed to elicit fluid from the nipple.

Nipple aspirator

Upon completion of the nipple aspiration procedure, subjects will undergo a nipple block with local anesthesia. The duct will be lavaged with the ductal lavage microcatheter. Samples will be immediately processed for shipping to Covance for WGS. Subjects will be contacted 24 hours and again 2 weeks after the procedure to collect any untoward effects of participating in the study.

Ductal lavage microcatheter

Blood will be drawn and immediately processed for shipping to Covance for WGS.

Blood draw

Dr. Susan Love, MD

The objective of this study is to determine whether we can use minimally invasive techniques to gain access to exfoliated ductal epithelial cells for whole genome sequencing.

1. To examine women with nipple aspiration, ductoscopy and ductal lavage and collect exfoliated cells from two ducts per woman.
2. To collect a blood sample at the time of the examination in order to obtain the woman's baseline genomic sequence.
3. De-identified samples will then have DNA and RNA extracted and whole genome sequencing and transcriptome analysis performed by Covance and Illumina.
4. Comparisons will be made within a breast (two ducts) and between the duct and blood as well as between women.

Despite the lack of anatomical clarity in the literature, Tibor Tot has postulated that breast cancer and DCIS are a lobar disease as the simultaneously or asynchronously appearing, often multiple in situ tumor foci are localized within a single "sick" lobe. This theory has some resonance in the molecular studies that have been done in the breast demonstrating that there are large "patches" of clonality even in normal breast tissue. Most of this work was based on microdissection, however, and assumes that adjacent duct profiles belong to the same lobe. In fact both Cooper and Going have shown intertwining of arborizing ducts from different independent lobes. This sets the stage for errors of interpretation in micro-dissected tissue.

Ductal lavage allows the cannulation and lavage of individual ducts and collection of 1,000- over 10,000 exfoliated cells that can be studied for molecular and genetic changes. Ductoscopy adds the ability to confirm that the duct has not been perforated and to brush the lining of the duct to increase cell yield. Real-time ultrasound can be used to confirm the ductal anatomy. With the combination of these minimally invasive techniques it is now possible to collect the cells needed to apply new genetic techniques and investigate the genome of the ductal epithelial cell.

While the methods for obtaining the ductal epithelial cells have been being developed similar advances have been made in whole genome sequencing technology. Knome®, a for-profit company, is now able to analyze ductal cells against blood to identify variants, including single nucleotide polymorphisms (SNP's), short and long insertions and deletions (indels), inversions, translocations, fusion genes and copy number variations (CNVs). Ingenuity Pathway Analysis can identify mRNA networks that can be driving pre-cancerous hyperplasia. Covance Genomics Laboratory (CAL) will perform DNA and RNA extraction, DNA QC and Next-Generation Sequencing on the Illumina platform.

With the combination of these minimally invasive techniques and Next-Generation Sequencing we will be able to test our hypothesis that it is now possible to interrogate the genetic sequence of a single normal duct and to compare it to the sequence in the blood to identify early epithelial mutations. In addition by comparing the sequence of two ducts in one breast we can gain insight into whether each duct is clonal or the whole breast shares the same genetic pattern. And finally, understanding the pathways that are activated in pre-cancerous duct lesions can provide targets for intraductal treatment programs.

Whole blood, nipple aspirate fluid, ductal lavage fluid

The Breast Duct: Pilot Study of Genomic Sequencing of Exfoliated Ductal Cells Obtained Through Endoscopy and Lavage

Extract high-quality DNA and RNA from human whole blood and ductal lavage (DL) samples. Assess QC and Quantitation of extracted RNA and DNA samples. Assess QC and Quantitation of libraries generated by CGL for Whole Genome DNA-seq and RNA sequencing assays. Sequence prepared libraries using the Illumina Next Generation Sequencing platform.

Covance

Illumina, Inc.

Atossa Therapeutics, Inc.

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Prostatic Intraepithelial Neoplasia

Anticoagulants

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
The Breast Duct: Pilot Study of Genomic Sequencing of Exfoliated Ductal Cells Obtained Through Endoscopy and Lavage	NCT02121873	Breast Cancer Preneoplastic C... Ductal Carcinom...	Nipple aspirato... Ductal lavage m... Blood draw	18 Years -	Atossa Therapeutics, Inc.
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

Spots Global Cancer Trial Database for preneoplastic conditions