Phase I Trial of Endoxifen Gel Versus Placebo in Women Undergoing Breast Surgery
Condition: Breast Ductal Carcinoma In Situ; Breast Lobular Carcinoma In Situ; Stage 0 Breast Cancer AJCC v6 and v7; Stage I Breast Cancer AJCC v7; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage II Breast Cancer AJCC v6 and v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7; Stage III Breast Cancer AJCC v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIC Breast Cancer AJCC v7
MeSH terms: Carcinoma; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Ductal; Carcinoma, Intraductal, Noninfiltrating; Breast Carcinoma In Situ; Carcinoma, Lobular; Carcinoma, Ductal, Breast
Intervention: Endoxifen Hydrochloride; Placebo Administration; Questionnaire Administration
Intervention description: Apply to the skin; Apply to the skin; Ancillary studies
Intervention MeSH terms: Tamoxifen
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 32.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase I trial studies the side effects and best dose of endoxifen
      hydrochloride in treating participants who are undergoing breast surgery. Endoxifen
      hydrochloride may treat or reduce the risk of breast cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Women scheduled for unilateral or bilateral mastectomy for breast cancer therapy,
             pathology confirmed stage 0-III (including ductal carcinoma in situ), or prophylaxis
             (BRCA1/2 mutation carriers, women with strong family history or lobular carcinoma in
             situ or other conditions where prophylactic mastectomy has been elected)

          -  Age >= 18 years (since breast cancer is not a pediatric disease and no safety data are
             available for ENX use in children)

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)

          -  Total bilirubin < 1.5 x upper limit of normal (ULN) (in women with prior documented
             bilirubin elevations consistent with Gilbert's syndrome, total bilirubin up to 3 x ULN
             will be allowed)

          -  Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) <
             2.5 x ULN

          -  Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2.5 x
             ULN

          -  Creatinine < 2 x ULN

          -  Alkaline phosphatase < 2.5 x ULN

          -  Blood urea nitrogen < 2 x ULN

          -  Ability to understand and the willingness to sign a written informed consent document
             which includes a requirement to apply study agent to sensitive body parts daily

          -  Willingness and ability to schedule mastectomy 21-28 days following start of study
             agent; women with breast implants may participate

          -  Willingness to avoid exposing breast skin to natural or artificial sunlight (i.e.
             tanning beds) for the duration of study agent dosing

          -  Negative urine or serum pregnancy test result, for participants of child bearing
             potential; female of child-bearing potential is any woman (regardless of sexual
             orientation, whether she has undergone a tubal ligation, or remains celibate by
             choice) who meets the following criteria: has not undergone a hysterectomy or
             bilateral oophorectomy; AND has had a menstrual period at any time in the preceding 12
             consecutive months)

          -  The effects of topical ENX gel on the developing human fetus are unknown; for this
             reason, women of child-bearing potential and their male partners must agree to use
             effective forms of birth control (abstinence is not an allowed method) prior to study
             entry and for the duration of study participation; should a woman become pregnant or
             suspect she is pregnant while participating in this study, she should inform her study
             physician immediately

        Exclusion Criteria:

          -  The presence of gross skin invasion/ulceration by the breast cancer, or inflammatory
             changes with skin edema AND erythema; Note: Paget's disease is permitted

          -  Women receiving a "nipple delay" procedure prior to mastectomy

          -  Women with skin diseases (psoriasis, eczema)

          -  A history of thromboembolic disorder

          -  Endometrial intraepithelial neoplasia (also known as atypical hyperplasia) or a high
             risk of uterine cancer, defined here as known carriers of Lynch syndrome mutations
             (MLH1, MSH2, MSH6, PMS2)

          -  Participants may not have received any other investigational agents in the previous 3
             months

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to tamoxifen

          -  Taken tamoxifen or other selective estrogen/progesterone receptor modulators
             (SERMs/SPRMs) within two years prior to entering study or been required to discontinue
             SERM therapy due to thromboembolic or uterine toxicity

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  History of prior breast cancer-specific therapy within the previous 2 years
             (chemotherapy, radiation, anti-HER2 agents, endocrine agents, everolimus, CDK4-6
             inhibitors); previous unilateral radiation of the contralateral side in women
             scheduled for mastectomy is allowed; study gel will be applied to both breasts

          -  History of prior mastectomy

          -  Pregnant or breastfeeding

          -  Patients receiving neoadjuvant chemotherapy with curative intent

          -  Men are excluded from this study since breast cancer is men is rare and there are no
             data regarding skin penetration of topical breast cancer prevention agents through
             male chest wall skin (which is thicker and harrier than female chest wall skin)

          -  Current users of other topical medications on the breast skin must be willing and able
             to discontinue use for the duration of participation; body lotion and other
             non-medicinal topical compounds may be applied > 4 hours after study gel application