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

Overview

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

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Double (Care Provider, Investigator)
  • Study Primary Completion Date: December 31, 2026

Detailed Description

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.

Interventions

  • Drug: Tamoxifen
    • Oral Tamoxifen 10 mg/day
  • Drug: Topical 4-OHT( 4-hydroxytamoxifen)gel 2 mg/each breast/day
    • Topical 4-OHT (4-hydroxytamoxifen) gel 2 mg/each breast/day
  • Drug: Placebo
    • placebo pill or placebo gel

Arms, Groups and Cohorts

  • Experimental: Oral Tamoxifen 10 mg/day
    • Oral Tamoxifen 10 mg/day
  • Experimental: Topical 4-OHT (4-hydroxytamoxifen) gel 2 mg/each breast/day
    • Topical 4-OHT (4-hydroxytamoxifen) gel 2 mg/each breast/day +oral placebo
  • Experimental: Control
    • Oral and gel placebo

Clinical Trial Outcome Measures

Primary Measures

  • The purpose of this research is to evaluate short-term changes in background breast tissue induced by oral tamoxifen or 4-OHT gel in women with atypical hyperplasia or lobular carcinoma in situ (LCIS).
    • Time Frame: 48 months
    • Treatment Evaluation/Measurement of Effect

Participating in This Clinical Trial

Inclusion Criteria

  • Willing to return to enrolling institution for follow-up – Willing to complete required testing – Ability to complete questionnaire by themselves or with assistance – Female (sex that was assigned at birth) – Ipsilateral intact breast with histology confirmation of atypical ductal or lobular hyperplasia, or LCIS, within the last 12 months, whether surgically excised or not. – Eastern Cooperative Oncology Group (ECOG) performance status ≤1 – Willingness to agree to use ONE effective form of birth control (abstinence is not an allowed method) prior to study entry and for the duration of study participation, and for 2 months following the last dose of study medications. Effective birth control methods are: copper IUD [intrauterine device], diaphragm/cervical cap/shield, spermicide, contraceptive sponge, condoms. Women of childbearing potential must have a negative pregnancy test within five days before starting study medications. Should a participant become pregnant or suspect she is pregnant while participating in this study; the participant should inform the study physician immediately. – Willingness to avoid exposing breast skin to natural or artificial sunlight (i.e. tanning beds) for the duration of the study. – Participants must have acceptable organ and marrow function as defined below within 30 days of randomization: judged by treating physician's evaluation of baseline laboratory data. – Negative urine pregnancy test, if of childbearing potential. and / or FSH to verify menopausal status. Exclusion Criteria:
  • Clinically suspicious mass/lesions Breast cancer in the past 5 years. – Prior thromboembolism within last 5 years (history of varicose veins and superficial phlebitis is allowed) Current pregnancy or lactation History of other prior breast cancer-specific therapy within the previous 2 years (chemotherapy, anti-HER2 agents, endocrine agents, everolimus, CDK4-6 inhibitors). – Cytotoxic chemotherapy for any indication in last 2 years. – Prior use of SERMS or AIs including tamoxifen, raloxifene, anastrozole, letrozole, or exemestane for prevention or therapy within 5 years. – Exogenous sex steroid, including oral contraceptive pill use within 1 month prior to research core needle biopsy (CNB). – Use of vaginally administered estrogens and hormone coated IUD such as Mirena is permitted History of any prior ipsilateral breast radiotherapy. Previous unilateral radiation of the contralateral side is allowed. – Skin lesions on the breast that disrupt the stratum corneum (eg eczema, ulceration). – History of endometrial neoplasia – Current smoker. Cessation for at least 6 weeks – Current users of potent inhibitors of tamoxifen metabolism. The potent inhibitors of tamoxifen metabolism are: bupropion, cinacalcet, fluoxetine, paroxetine, quinidine. – Participants may not be receiving any other investigational agents within 90 days of enrollment or during this study. – History of allergic reactions to tamoxifen. – Uncontrolled intercurrent illness that in the judgement of the treating physician would make them unsuitable for study participation – Anticoagulation meds and clinical concern for discontinuing meds for study research biopsy. – Identification of a clinically suspicious mass on examination.
  • Gender Eligibility: Female

    Minimum Age: 18 Years

    Maximum Age: 80 Years

    Are Healthy Volunteers Accepted: No

    Investigator Details

    • Lead Sponsor
      • Amy C. Degnim
    • Provider of Information About this Clinical Study
      • Sponsor-Investigator: Amy C. Degnim, Principal Investigator – Mayo Clinic
    • Overall Official(s)
      • Amy Degnim, MD, Principal Investigator, Mayo Clinic
    • Overall Contact(s)
      • Denice Gehling, RN, 507-538-1628, gehling.denice@mayo.edu

    Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

    At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.