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

Amy C. Degnim (Other)
Overall Status
CT.gov ID

Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
  • Drug: Tamoxifen
  • Drug: Topical 4-OHT( 4-hydroxytamoxifen)gel 2 mg/each breast/day
  • Drug: Placebo
Phase 2/Phase 3

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.

Study Design

Study Type:
Anticipated Enrollment :
104 participants
Intervention Model:
Parallel Assignment
Intervention Model Description:
Subjects will be randomized 2:2:1 with either Oral Tamoxifen 10 mg/day gel placebo, Topical 4-OHT gel 2 mg/each breast/day oral placebo, or Control Oral and gel placebo for 4 weeks of treatment.Subjects will be randomized 2:2:1 with either Oral Tamoxifen 10 mg/day gel placebo, Topical 4-OHT gel 2 mg/each breast/day oral placebo, or Control Oral and gel placebo for 4 weeks of treatment.
Double (Care Provider, Investigator)
Masking Description:
Subjects with be randomized by MedidataRave and Pharmacy.
Primary Purpose:
Official Title:
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
Actual Study Start Date :
Jul 26, 2021
Anticipated Primary Completion Date :
Dec 31, 2026
Anticipated Study Completion Date :
Dec 31, 2026

Arms and Interventions

Arm Intervention/Treatment
Experimental: Oral Tamoxifen 10 mg/day

Oral Tamoxifen 10 mg/day

Drug: Tamoxifen
Oral Tamoxifen 10 mg/day
Other Names:
  • Oral tamoxifen
  • 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

    Drug: Topical 4-OHT( 4-hydroxytamoxifen)gel 2 mg/each breast/day
    Topical 4-OHT (4-hydroxytamoxifen) gel 2 mg/each breast/day
    Other Names:
  • Topical gel
  • Experimental: Control

    Oral and gel placebo

    Drug: Placebo
    placebo pill or placebo gel
    Other Names:
  • placebo pill
  • placebo gel
  • Outcome Measures

    Primary Outcome Measures

    1. 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). [48 months]

      Treatment Evaluation/Measurement of Effect

    Eligibility Criteria


    Ages Eligible for Study:
    18 Years to 80 Years
    Sexes Eligible for Study:
    Accepts Healthy Volunteers:
    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.

    Contacts and Locations


    Site City State Country Postal Code
    1 Mayo Clinic Rochester Minnesota United States 55905

    Sponsors and Collaborators

    • Amy C. Degnim


    • Principal Investigator: Amy Degnim, MD, Mayo Clinic

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:


    None provided.
    Responsible Party:
    Amy C. Degnim, Principal Investigator, Mayo Clinic
    ClinicalTrials.gov Identifier:
    Other Study ID Numbers:
    • 19-011444
    First Posted:
    Sep 30, 2020
    Last Update Posted:
    Sep 17, 2021
    Last Verified:
    Sep 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Plan to Share IPD:
    Studies a U.S. FDA-regulated Drug Product:
    Studies a U.S. FDA-regulated Device Product:
    Product Manufactured in and Exported from the U.S.:
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Sep 17, 2021