Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Symptoms and General Pathology

Carcinoma

Breast Neoplasms

Carcinoma, Ductal

Hyperplasia

Carcinoma in Situ

Carcinoma, Lobular

Carcinoma, Intraductal, Noninfiltrating

Carcinoma, Ductal, Breast

Breast Carcinoma In Situ

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Breast Diseases

Skin Diseases

Adenocarcinoma

Antineoplastic Agents

All Drugs and Chemicals

Bexarotene

Group 1 will apply 10mg bexarotene topically to one breast QOD for 4 weeks; Group 2 will apply 10mg bexarotene topically to one breast QOD for 1 week and then daily for 3 weeks after confirmation that toxicity is at an acceptable range; Group 3 will apply 10mg bexarotene topically to one breast QOD for 1 week, then daily for 1 week, and then 20mg daily for 2 weeks after confirmation that toxicity is at an acceptable range.

Questionnaire Administration

Parijatham (Priya) S Thomas

This phase I trial studies the side effects and best dose of bexarotene in preventing breast cancer in patients at high risk for breast cancer. Bexarotene belongs to a class of drugs that are called rexinoids, and it may reduce the incidence of breast tumors.

PRIMARY OBJECTIVES:

I. To determine the recommended phase II dose of topical bexarotene 1% (weight by weight \[w/w\]) gel for evaluation in healthy women. (Dose Escalation Group) II. Conduct an intervention of topical 1% bexarotene gel to an unaffected breast of healthy women at high risk for breast cancer for 4 weeks at the maximum tolerated dose (MTD) as determined during the dose escalation group phase to assess bexarotene concentration in the breast tissue. (Dose Expansion Group)

SECONDARY OBJECTIVES:

I. To detect bexarotene concentration in the serum at baseline and at 4 weeks of treatment.

II. To detect bexarotene concentration in the breast tissue at 4 weeks of treatment in the dose escalation group.

III. To investigate the effects of topical bexarotene on serum biomarkers, we will determine the change from baseline in i) lipid biomarkers (total cholesterol, triglycerides, low density lipoprotein \[LDL\], high density lipoprotein \[HDL\]), ii) thyroid function biomarkers (thyroid stimulating hormone \[TSH\], T4, T3), iii) calcium.

EXPLORATORY OBJECTIVE:

I. To examine changes in gene expression associated with retinoid action. (Dose Expansion Group)

OUTLINE: This is a dose-escalation study.

Group 1 will apply 10mg bexarotene topically to one breast every other day (QOD) for 4 weeks; Group 2 will apply 10mg bexarotene topically to one breast every other day (QOD) for 1 week and then daily for 3 weeks after confirmation that toxicity is at an acceptable range; Group 3 will apply 10mg bexarotene topically to one breast every other day (QOD) for 1 week, then daily for 1 week, and then 20mg daily for 2 weeks after confirmation that toxicity is at an acceptable range.

After completion of study treatment, patients are followed up at 30 days.

Bexarotene in Preventing Breast Cancer in Patients at High Risk for Breast Cancer

A Phase I Dose Escalation Study of Topical Bexarotene in Women at High Risk for Breast Cancer

One of the four cores collected from the core biopsies from baseline (in dose expansion cohort only) and post treatment (all dose expansion cohort participants and optional for dose escalation group) will be formalin-fixed and paraffin embedded (FFPE) for histological analysis. One of the four cores collected from the core biopsies from baseline and post treatment will be placed in RNALater and utilized for gene expression of ribonucleic acid (RNA) biomarkers. Gene expression will be performed.

Dose Limiting Toxicity (DLT) is defined as a grade 2 skin adverse event that persists for at least 6 days or any grade 3 or greater adverse event possibly, probably, or definitely related to the study drug. In addition, a DLT will be a grade 2 skin adverse event that recurs and persists for at least 3 days.

Serum biomarkers to be tested will be total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein, thyroid-stimulating hormone, T4, T3, and calcium. Will be summarized using mean, standard deviation and median (range) for continuous variables at each time point. Wilcoxon rank-sum test may be used to examine the difference of continuous variables between participants' characteristics groups. Will be plotted as functions of time (baseline, week 1, week 2, and week 4). Linear mixed effect model will be applied to model the biomarker change over time for all participants. Appropriate transformation and regression model will be used to ensure the model fit.

Plasma concentrations of bexarotene were evaluated in all participants at baseline and at end of study. Plasma samples: ND = Not detected (below the quantitation limit of 0.5 ng/mL) TDL = Trace levels detected (below the LOQ of 0.5ng/mL; estimated value)

Breast tissue concentrations were available only in those women who underwent breast biopsies. Tissue samples: Not detected (below the quantitation limit of 2.5 ng/g for a 10mg sample) and Trace levels detected (below the LOQ of 2.5ng/g; estimated value).

National Cancer Institute (NCI)

Dose Level 1

Dose Level 2

Expansion Cohort

Total

40-49 years

50-59 years

60-69 years

70 and over years

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Menopause

Priya Thomas,MD-Associate Professor, Clinical Cancer Prevention

Maculopapular rash with pruritus at application site

Erythema/redness at application site

Bexarotene 1 % gel 10 mg every other day.

Number of Participants With Incidence of Adverse Events (Dose Limiting Toxicities)

Number of Participants With Changes in Markers of Systemic Toxicity

Plasma Baseline Visit

Plasma End of Treatment Visit

Number of Participants With Trace Level of Bexarotene Concentration in Plasma Detected

Non Detected

Trace Levels Detected

Quantitation limit of 2.6-10 ng/g

Quantitation limit of 11-20 ng/g

Quantitation limit of 21-30 ng/g

Quantitation limit of >30 ng/g

Number of Participants With Bexarotene Concentration in Tissue

Tissue Markers

Overall Study

Bone Density Conservation Agents

Tamoxifen

Afimoxifene

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Selective Estrogen Receptor Modulators

Estrogen Receptor Modulators

Topical 4-OHT (4-hydroxytamoxifen) gel 4 mg/each breast/day

+oral placebo

Topical 4-OHT (4-hydroxytamoxifen) gel 4 mg/each breast/day

Topical 4-OHT( 4-hydroxytamoxifen)gel 4 mg/each breast/day

Placebo

Denice Gehling, RN

Lisa R Seymour

Zachary Feldman

Seema Khan, M.D.

Denice Gehling, R.N.

Lisa Seymour, B.S

Amy Degnim, M.D.

The investigators plan to prospectively study breast tissue changes after a short course of Tamoxifen (Tam).

Women with atypical hyperplasia (AH) and lobular carcinoma in situ (LCIS) are at increased risk of breast cancer (BC) (\~1-2 % per year). Over two decades ago, placebo-controlled randomized trials established that oral tamoxifen (20 mg/day) reduces breast cancer risk by 50% in generally defined high risk women, with \~70% reduction in women at high risk specifically due to atypical hyperplasia.\[1\] Years later, the side effects and toxicity of oral tamoxifen at 20 mg/day remain a significant barrier to its uptake and longterm compliance.\[2, 3\] To address the issue of toxicity, two main strategies have been pursued: 1) using a lower dose of oral tamoxifen, and 2) using a topical formulation of tamoxifen to avoid systemic side effects. The investigators will perform a prospective study of women with AH or LCIS who will take a short course of prevention therapy; breast tissue samples will be evaluated pre- and post-therapy to identify and evaluate very early biomarkers of response. The overall goal of the study is to evaluate short-term changes in background breast tissue induced by either low-dose oral tamoxifen or topical 4-OHT gel in women with AH or LCIS.

Subjects will be randomized 2:2:1 with either Oral Tamoxifen 10 mg/day

* gel placebo, Topical 4-OHT gel 4 mg/each breast/day
* oral placebo, or Control Oral and gel placebo for 4 weeks of treatment.

Subjects with be randomized by MedidataRave and Pharmacy.

Oral Tamoxifen vs. TamGel vs. Control in Women With Atypical Hyperplasia or Lobular Carcinoma In Situ

A Phase IIB Randomized Trial of Oral Tamoxifen vs. Topical 4-hydroxytamoxifen Gel vs. Control in Women With Atypical Hyperplasia or Lobular Carcinoma In Situ

Treatment Evaluation/Measurement of Effect

Amy C. Degnim

Principal Investigator

Patients complete physical measurements every 6 months and complete questionnaires annually for 5 years. Patients are followed up annually in years 5-10.

Follow-Up

Physical Examination

The Ohio State University Comprehensive Cancer Center

Sagar D. Sardesai, MSPH, PhD

Sagar D Sardesai, MSPH, PhD

This study evaluates the association of dietary inflammatory potential with breast cancer risk. Information collected in this study may help doctors to identify modifiable risk factors, screen high risk patients early, improve prevention strategies, and provide timely intervention for early therapeutic management as needed.

PRIMARY OBJECTIVE:

I. To evaluate the association of dietary inflammatory potential (measured by Empirical Dietary Inflammatory Pattern \[EDIP\] score) at baseline using Diet History Questionnaire III (DHQIII) food frequency questionnaire (FFQ) with the incidence of breast cancer in high risk women established in the breast cancer prevention clinic at Ohio State University Comprehensive Cancer Center (OSUCCC) - James.

SECONDARY OBJECTIVES:

I. To evaluate changes in inflammatory potential of diet (EDIP score) from baseline FFQ and subsequently administered annually, and determine how these dietary changes relate to breast cancer risk longitudinally.

II. To evaluate associations of dietary inflammatory potential (EDIP score) with measures of obesity including bone marrow index (BMI) (obesity defined as \>= 30, non-obese \< 30) and abdominal/visceral adiposity (waist-hip ratio \[WHR\] \> 0.85 or waist circumference \[WC\] \>= 80 cm in women) at baseline.

III. To evaluate the association of dietary inflammatory potential (EDIP score) with mammographic breast density by breast imaging reporting and data system (BIRADS) classification at baseline.

CORRELATIVE OBJECTIVES:

I. To evaluate the correlation of baseline and annual inflammatory blood-based biomarkers (IL-6, hsCRP, adiponectin, leptin, insulin resistance \[Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)\]) with: a) dietary inflammatory potential (EDIP score) and b) visceral adiposity (waist-hip ratio \> 0.85 or waist circumference \>= 80 cm in women) and c) mammographic breast density by BIRADS classification at baseline and longitudinally (every year for 5 years).

II. To evaluate the association of baseline circulating biomarkers (hsCRP, TNF-a, insulin resistance \[HOMA-IR\]) and breast cancer incidence longitudinally in high risk patients.

EXPLORATORY OBJECTIVES:

I. Describe utilization of supplemental imaging by type, including breast magnetic resonance imaging (MRI), automated breast ultrasound (ABUS) and contrasted-enhanced spectral mammography (CESM), in all enrolled women.

II. Describe use of chemoprevention strategies (initiation of tamoxifen, raloxifene, aromatase inhibitor (AI), or other) in women presenting at the high risk clinic at OSUCCC-James.

OUTLINE:

Patients complete physical measurements every 6 months and complete questionnaires annually for 5 years. Patients are followed up annually in years 5-10.

Impact of Dietary Inflammatory Potential on Breast Cancer Risk

Longitudinal Study Evaluating the Impact of Dietary Inflammatory Potential on Breast Cancer Risk in a Cohort of Women Followed in the Breast Cancer Prevention Clinic at the Ohio State University Comprehensive Cancer Center- James Cancer Hospital and Solove Research Institute

Proportion of patients initiating chemoprevention within 12 months of enrollment will be summarized.

Will be expressed as the means, medians and standard deviations (for continuous variables) or frequencies and percentages (for categorical variables). To assess the association of baseline Empirical Dietary Inflammatory pattern (EDIP) scores with breast cancer incidence, Cox proportional hazards regression will be used to estimate the hazard ratio (HR) and its 95% confidence interval (CI).

Will be expressed as the means, medians and standard deviations (for continuous variables) or frequencies and percentages (for categorical variables).

Will be measured by breast imaging reporting and data system. Will be expressed as the means, medians and standard deviations (for continuous variables) or frequencies and percentages (for categorical variables).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Bexarotene in Preventing Breast Cancer in Patients at High Risk for Breast Cancer	NCT03323658	Breast Atypical... Breast Atypical... Breast Ductal C... Breast Lobular ... Invasive Breast...	Bexarotene Questionnaire A...	18 Years -	National Cancer Institute (NCI)
Oral Tamoxifen vs. TamGel vs. Control in Women With Atypical Hyperplasia or Lobular Carcinoma In Situ	NCT04570956	Breast Atypical... Breast Lobular ... Breast Atypical...	Tamoxifen Topical 4-OHT( ... Placebo	18 Years - 80 Years	Mayo Clinic
Impact of Dietary Inflammatory Potential on Breast Cancer Risk	NCT05178498	Breast Atypical... Breast Atypical... Breast Carcinom... Breast Lobular ... Breast Sclerosi...	Follow-Up Physical Examin... Questionnaire A...	18 Years -	Ohio State University Comprehensive Cancer Center
Bexarotene in Preventing Breast Cancer in Patients at High Risk for Breast Cancer	NCT03323658	Breast Atypical... Breast Atypical... Breast Ductal C... Breast Lobular ... Invasive Breast...	Bexarotene Questionnaire A...	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for breast atypical lobular hyperplasia