4-Hydroxytamoxifen or Tamoxifen Citrate in Treating Women With Newly Diagnosed Ductal Breast Carcinoma in Situ
Condition: Ductal Breast Carcinoma in Situ; Estrogen Receptor-positive Breast Cancer
MeSH terms: Carcinoma; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Ductal, Breast; Breast Carcinoma In Situ; Carcinoma, Intraductal, Noninfiltrating
Intervention: oral placebo; afimoxifene; tamoxifen citrate; placebo gel
Intervention description: Oral placebo taken daily for 4-10 weeks.; 2mg/breast applied daily in the form of a gel for 4-10 weeks.; 20mg oral tamoxifen taken daily (taken as two (2) 10mg capsules) for 4-10 weeks.; Placebo gel applied to breasts daily for 4-10 weeks.
Intervention MeSH terms: Tamoxifen; Afimoxifene
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 27.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial is studying 4-hydroxytamoxifen to see how well it works
      compared with tamoxifen citrate in treating women with newly diagnosed ductal breast
      carcinoma in situ. Estrogen can cause the growth of breast cancer cells. Hormone therapy
      using tamoxifen may fight breast cancer by blocking the use of estrogen by the tumor cells.
      It is not yet known whether topical tamoxifen causes less damage to normal tissue than
      systemic tamoxifen in treating patients with ductal carcinoma in situ.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Diagnosis of hormone receptor positive (more than 5% cells staining for ER + and/ or
             PR +), any grade (using definition of Page and Lagios) ductal carcinoma in situ (DCIS)
             with or without evidence of microinvasion on diagnostic core needle biopsy within the
             previous 60 days.

          2. Women of age ≥ 18 years. Because no dosing or adverse event data are currently
             available on the use of 4-hydroxytamoxifen in participants <18 years of age, children
             are excluded from this study but will be eligible for future pediatric trials, if
             applicable.

          3. ECOG performance status ≥1 (Karnofsky ≥70%)

          4. Participants must have normal organ and marrow function as defined below:

               1. Leukocytes≥3,000/uL

               2. Absolute neutrophil count (ANC)≥1,500/uL

               3. Platelets≥100,000/uL

               4. Total bilirubin within normal institutional limits

               5. AST (SGOT)/ALT (SGPT)≤1.5 X institutional ULN

               6. Creatinine within normal institutional limits

          5. Women of child-bearing potential must agree to practice barrier birth control,
             abstinence, or use non-hormonal IUDs from the time that the first pregnancy test is
             performed throughout the duration of the study and for three months after cessation of
             study drug. Should a woman become pregnant or suspect she is pregnant while
             participating in this study, she should inform her study physician immediately.

          6. Ability to understand and the willingness to sign a written informed consent document.

          7. Ability and willingness to schedule surgical resection of DCIS lesion for 4-10 weeks
             (28-70 days) following the start of study agent.

          8. Willingness to avoid exposing breast skin to natural or artificial sunlight (i.e.
             tanning beds) for the 4-10 weeks of study agent dosing.

        Exclusion Criteria:

          1. Prior history of, or at high risk to develop, thromboembolic disease will be excluded.

          2. Must not have taken exogenous sex hormones since biopsy diagnosing DCIS and must agree
             not to use exogenous sex hormones while on study.

          3. Must not have taken tamoxifen or other selective estrogen receptor modulators (SERMs)
             within 2 years prior to entering the study. Women who have discontinued SERM therapy
             because of thromboembolic or uterine toxicity, will be excluded regardless of duration
             of use.

          4. May not be receiving any other investigational agents.

          5. History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to 4-hydroxytamoxifen or tamoxifen.

          6. 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.

          7. Pregnant women are excluded from this study because tamoxifen and 4-hydroxytamoxifen
             has the potential for teratogenic or abortifacient effects. Women are excluded from
             enrolling within 3 months of the most recent pregnancy. Women must avoid becoming
             pregnant in the 3 months following the use of study agent.

          8. Women must not have breastfed within three months prior to DCNB. Women who are breast
             feeding are excluded from entry into this trial because there is an unknown but
             potential risk for adverse events in nursing infants secondary to treatment of the
             mother with tamoxifen or 4-hydroxytamoxifen. Women must agree to forego breastfeeding
             for three months following the use of study agent.

          9. Must not have any dermatologic conditions resulting in skin breakdown in the area of
             gel application.

         10. Must not have a history of previous ipsilateral radiation to the affected breast.

         11. Must not have had a breast reduction or augmentation within the 6 months prior to
             first dose of study agents. Patients who have had breast implants more than 6 months
             prior to first dose of study agents will be eligible.