Oral Tamoxifen vs. TamGel vs. Control in Women With Atypical Hyperplasia, Lobular Carcinoma In Situ, or Increased Breast Cancer Risk

NCT04570956 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: CA2376075R01CA237607-0519-011444
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 3

Brief Summary

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

Conditions

Breast Atypical Hyperplasia; Breast Lobular Carcinoma in Situ; Breast Atypical Lobular Hyperplasia; Breast Carcinoma

Outcome Measures

Primary Outcomes (1)

• Change in Median Lobular Ki67 From Pre-Tamoxifen Breast Biopsy to On-Tamoxifen Biopsy With 4 Weeks of Intervention

  All patients received an oral pill and a topical gel. Prior to assessing non-inferiority of 4-OHT Gel compared to Oral Tamoxifen, treatment effect was assessed within each group by testing for a significant reduction in median lobular Ki67 between PreTam and OnTam biopsy. Median lobular Ki67 is assessed using the percentage of cells stained across all lobules separately at PreTam and OnTam timepoints, evaluated for a difference in median calculated change.

  Pre-biopsy to post-biopsy following 4 weeks of intervention

Study Arms (3)

Oral Tamoxifen 10 mg/day

EXPERIMENTAL

Oral Tamoxifen 10 mg/day

Drug: Tamoxifen; Other: Questionnaire Administration

Topical 4-OHT (4-hydroxytamoxifen) gel 4 mg/each breast/day

EXPERIMENTAL

Topical 4-OHT (4-hydroxytamoxifen) gel 4 mg/each breast/day +oral placebo

Drug: Topical 4-OHT( 4-hydroxytamoxifen)gel 4 mg/each breast/day; Other: Questionnaire Administration

Control

EXPERIMENTAL

Oral and gel placebo

Drug: Placebo; Other: Questionnaire Administration

Interventions

Tamoxifen DRUG

Oral Tamoxifen 10 mg/day

Also known as: Oral tamoxifen

Oral Tamoxifen 10 mg/day

Placebo DRUG

placebo pill or placebo gel

Also known as: placebo pill, placebo gel

Control

Questionnaire Administration OTHER

Ancillary studies

Control; Oral Tamoxifen 10 mg/day; Topical 4-OHT (4-hydroxytamoxifen) gel 4 mg/each breast/day

Topical 4-OHT( 4-hydroxytamoxifen)gel 4 mg/each breast/day DRUG

Topical 4-OHT (4-hydroxytamoxifen) gel 4 mg/each breast/day

Also known as: Topical gel

Topical 4-OHT (4-hydroxytamoxifen) gel 4 mg/each breast/day

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 lobular carcinoma in situ (LCIS), within the last 12 months, whether surgically excised or not.; OR neither AH nor LCIS but increased breast cancer risk defined as either:
• Gail model (Breast Cancer Risk Assessment Tool) 5 year breast cancer risk of \>= 3%, or
• International Breast Intervention Study model 10 year breast cancer risk of \>= 5%.
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%)
• The effects of topical afimoxifene (4-OHT) gel on the developing human fetus at the recommended therapeutic dose are unknown. However, oral tamoxifen is Pregnancy Category D-positive evidence of human fetal risk. For this reason, and because triphenylethylene antiestrogens, including tamoxifen, are known to be teratogenic, women of childbearing potential and their male partners must agree to use at least 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 (participant can resume oral birth control pills for effective birth control measures after post-treatment biopsy is done). Effective birth control methods during treatment are: copper and Mirena intrauterine device (IUD), diaphragm/cervical cap/shield, spermicide, contraceptive sponge, condoms. Tubal Ligation is an acceptable method of birth control. Women of childbearing potential must have a negative pregnancy test within five days before starting study medications. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her 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 judged by treating physician's evaluation of baseline laboratory data.
• Negative pregnancy (serum or urine) test if of childbearing potential and/or follicle stimulating hormone (FSH) to verify menopausal status.

You may not qualify if:

• Clinically suspicious mass/lesions
• Breast cancer in the past 5 years.
• Patients with any history of venous thromboembolic disease, regardless of timeframe (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 selective estrogen receptor modulator (SERMS) or AIs including tamoxifen, raloxifene, anastrozole, letrozole, or exemestane for prevention or therapy within the past 5 years unless:
• Use was less than 6 months duration in the past 5 years and not used in the 1 year prior to enrollment, or
• Use was no greater than 2 months duration in the past 1 year and not used in the 6 months prior to enrollment.
• Exogenous sex steroid, including oral contraceptive pill use within 1 month prior to pretreatment breast biopsy. 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 (e.g., 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.

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Northwestern University

Evanston, Illinois, 60208, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MD Anderson Cancer center at Cooper

Camden, New Jersey, 08103, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Breast Carcinoma In Situ; Breast Neoplasms

Interventions

Tamoxifen; Gels

Condition Hierarchy (Ancestors)

Carcinoma in Situ; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Colloids; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations

Results Point of Contact

• Title: Amy C. Degnim, MD
• Organization: Mayo Clinic

degnim.amy@mayo.edu

507-284-2511

Study Officials

• Amy Degnim, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Subjects with be randomized by MedidataRave and Pharmacy.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Subjects will be randomized 2:2:1 with either Oral Tamoxifen 10 mg/day * gel placebo, Topical 4-OHT gel 4 mg/each breast/day * oral placebo, or Control Oral and gel placebo for 4 weeks of treatment.

Study Record Dates

• First Submitted: September 28, 2020
• First Posted: September 30, 2020
• Study Start: July 26, 2021
• Primary Completion: October 15, 2024
• Study Completion: October 15, 2024
• Last Updated: September 24, 2026
• Results First Posted: September 1, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)