Testing an Active Form of Tamoxifen (4-hydroxytamoxifen) Delivered Through the Breast Skin to Control Ductal Carcinoma in Situ (DCIS) of the Breast

Overview

NCT ID: NCT02993159
Sponsor Protocol Number: NWU2015-06-04

About this study

This randomized phase IIB trial studies how well tamoxifen or afimoxifene works in treating patients with estrogen receptor positive breast cancer. Estrogen can cause the growth of breast cancer cells. Hormone therapy using tamoxifen citrate or afimoxifene may fight breast cancer by blocking the use of estrogen by the tumor cells.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Screen-detected, ER positive DCIS of the breast proven on core needle biopsy, defined as 10% ER positive cells. Microinvasion will be allowed. The size of the DCIS in the core biopsy sample must be at least 4mm for a single core or total at least 5 mm if multiple cores are summed and must be estimated on the deepest step section (if step sections are taken).
  • Age ≥ 18 years. DCIS of the breast is almost exclusively an adult condition. Because no dosing or adverse event (AE) data are currently available on the use of tamoxifen in participants <18 years of age, children are excluded from this study.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 (Karnofsky ≥ 70%).
  • Participants must have acceptable organ and marrow function as defined below.  Baseline lab parameters are not standard of care for initiation of tamoxifen therapy; a minimal panel will therefore be appropriate:
    • Leukocytes ≥ 3,000/microliter;
    • Platelets ≥ 100,000/microliter;
    • Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN);
    • AST (SGOT)/ALT (SGPT) ≤ 1.5 × ULN;
    • Creatinine ≤ 1.5 x ULN.
  • The effects of topical 4-OHT gel on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because tamoxifen is known to be teratogenic, all heterosexually active women who may become pregnant must agree to use a reliable non-hormonal contraceptive method or a hormonal IUD during the study and for 2 months after completing study medications. Reliable nonhormonal methods of contraception include barrier contraception and an Intra-Uterine Device (IUD). Hormonal IUDs are also allowable methods of birth control.
    • Note: Women who had tubal ligation or had a partner who had undergone a vasectomy (and are monogamous) are eligible for the study and are not required to use barrier contraception.
  • Willingness to avoid exposing breast skin to natural or artificial sunlight (i.e., tanning beds) for the duration of the study.
  • Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria: 

  • Exogenous sex steroid use within 4 weeks prior to diagnostic core needle biopsy (DCNB). Use of vaginally administered estrogens and hormone coated IUD such as Mirena is permitted and use should continue until surgery.
  • History of any prior ipsilateral breast radiotherapy. Previous unilateral radiation of the contralateral side is allowed.
  • History of other prior breast cancer-specific therapy within the previous 2 years (chemotherapy, anti-HER2 agents, endocrine agents, everolimus, CDK4-6 inhibitors).
  • Skin lesions on the breast that disrupt the stratum corneum (e.g., eczema, ulceration).
  • History of endometrial neoplasia.
  • History of thromboembolic disease (history of varicose veins and superficial phlebitis is allowed).
  • Current smokers.
  • Current users of potent inhibitors of tamoxifen metabolism must be willing and able to discontinue use and switch to an alternative medication for the duration of participation, under the advice of their physician. If the physician believes the current medication is medically necessary, the participant will not be eligible. The potent inhibitors of tamoxifen metabolism are: bupropion, cinacalcet, fluoxetine, paroxetine, quinidine.
  • Prior use of SERMS or AIs including tamoxifen, raloxifene, anastrozole, letrozole, or exemestane for prevention or therapy within 5 years.
  • Participants may not be receiving any other investigational agents within 30 days of enrollment or during this study.
  • History of allergic reactions attributed to tamoxifen or compounds of similar chemical or biologic composition.
  • 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.
  • Pregnant women are excluded from this study. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with tamoxifen, breastfeeding should be discontinued by nursing mothers who agree to participate in the study.
  • Men are excluded from this study since DCIS of the breast is exceedingly rare in men, and there are no data regarding skin penetration of 4-OHT though male chest wall skin (which is thicker and hairier than female chest wall skin).

 

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