Retinoid 9cUAB30 in Producing a Biologic Effect in Patients With Early Stage Breast Cancer

PRIMARY OBJECTIVES:

I. Compare molecular analysis of pre- and post-treatment tissue samples of breast cancers of
patients treated with 14-28 days of oral retinoid X receptor (RXR)-selective retinoid 9cUAB30
(9 cUAB30) to demonstrate significantly reduced proliferation.

SECONDARY OBJECTIVES:

I. Determine if 14-28 days of oral RXR-selective 9c-UAB30 treatment increases apoptotic
index, as measured by TdT-mediated dUTP nick end labeling (TUNEL) assay.

II. Examine the differences in gene expression from baseline to post-exposure breast cancer
samples using a custom gene panel from Nanostring Technologies.

III. To examine if the maximum concentration (Cmax) and safety of 9cUAB30 in the first 6
participants is affected by reducing the number of capsules at the 240 mg dose level.

IV. To examine the Cmax of all participants at baseline and on the day of surgery.

V. Determine if treatment with 2-4 weeks of 9cUAB30 prior to surgery will increase activated
type I dendritic cells in peripheral blood.

VI. Determine if treatment with 2-4 weeks of 9cUAB30 prior to surgery will increase gene
expression of type I immune cells in the tumor immune environment of all participants except
the first 6.

VII. Assess the overall safety of 9cUAB30 in comparison with known retinoid toxicity.

OUTLINE:

Patients receive retinoid 9cUAB30 orally (PO) once daily (QD) for 14 to 28 days. Patients
then undergo tumor resection surgery.

After completion of study treatment, patients are followed up at 7 days and 4-5 weeks.

Inclusion Criteria:

- Eastern Cooperative Oncology Group (ECOG) performance status =< 1 or Karnofsky >= 70%

- Invasive breast cancer between 0.5 cm and 5 cm in size diagnosed by needle core
biopsy, estrogen receptor positive (ER+) or estrogen receptor negative (ER-), Her2neu
positive or negative

- White blood cells (WBC) >= 3000/mm^3

- Platelets >= 100,000/mm^3

- Hemoglobin > 10 g/dL

- Bilirubin =< upper limit of institutional normal

- Aspartate aminotransferase (AST) =< upper limit of institutional normal

- Creatinine within institutional normal limits

- Fasting triglycerides =< 1.5 x upper limit of normal (ULN)

- Fasting cholesterol =< 1.5 x ULN

- Participants must agree to discontinue all vitamin supplements while taking study
medication and for thirty days past the last dose of study medication

- Have not been treated with chemotherapy, biological therapy or breast radiotherapy

- Have never used tamoxifen, raloxifene, or other antiestrogen compounds

- Have not used exogenous hormone replacement therapy or oral contraception in the year
prior to diagnosis; the use of non-systemic estrogen (such as vaginal estrogen use) is
allowed

- Only postmenopausal women and some premenopausal women (as outlined below) will be
eligible; should a woman become pregnant or suspect she is pregnant while
participating in this study, she should inform her study physician immediately

- Women will be considered postmenopausal if one of the following is met:

- Prior bilateral oophorectomy

- 60 years of age or older

- Age less than 60 years; amenorrheic for 12 or more months; and follicle
stimulating hormone (FSH) and plasma estradiol in the postmenopausal range

- Premenopausal women without childbearing potential are eligible to participate if
one of the following criteria is met:

- Prior hysterectomy

- Prior fallopian tubal ligation (cut, tied, or sealed)

- Prior placement of permanent intratubal contraceptive devices (e.g. Essure)

- Participants must have the ability to understand, and the willingness to sign, a
written informed consent document

Exclusion Criteria:

- Participant taking medications that might interact with 9cUAB30

- Participant who has started or increased dosage of lipid-lowering agents in the last
30 days of enrollment; or are taking fibric acid (fenofibrate, gemfibrozil) lipid
lowering agents.

- Participant receiving any other investigational agents within 30-days of enrollment
nor during study participation

- Participant with a history of allergic reactions attributed to compounds of similar
chemical or biologic composition of retinoids

- Participant with an uncontrolled intercurrent illness including, but not limited to;

- Ongoing or active infection,

- Symptomatic congestive heart failure,

- Unstable angina pectoris,

- Cardiac arrhythmia,

- A persistent grade 3 hypertension (as defined as stage 2 hypertension with
systolic blood pressure [BP] >= 160 mm Hg or diastolic BP >= 100 mm Hg and
medical intervention indicated) based on the baseline and previous BP readings if
available

- Psychiatric illness/social situations that will limit compliance with study
requirements

- Participant who is breastfeeding or planning to breastfeed for a month post last dose
of study agent

- Participant known to be human immunodeficiency virus (HIV)-positive

- Participant with a history of a second cancer diagnosis or reoccurrence < 5 years from
study entry with the exception of a history of squamous or basal cell carcinoma of the
skin < 5 years from study entry will not be excluded from this study

- Participant's core biopsy slides suggest that later re-sectioning will not contain
sufficient tumor to allow for an adequate evaluation of Ki67 and TUNEL assays, at a
minimum