Topical Afimoxifene in Treating Patients With Breast Cancer Who Have Undergone Radiation Therapy on One Breast

NCT04009044 | Active Not Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: NU 18B05NCI-2019-03771P30CA060553
• Study Type: interventional
• Target: 156
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II trial studies how well topical afimoxifene works in treating patients with breast cancer who have undergone radiation therapy on one breast. Topical afimoxifene is a quick-drying medicated gel that may block the growth of breast cancer cells when applied to the breast skin. The purpose of this research is to determine what effect, if any, differences in skin type between women have on the delivery of topical afimoxifene to the breast tissue, and whether radiation affects the delivery of topical afimoxifene to breast tissue.

Conditions

Cancer Survivor; Ductal Breast Carcinoma In Situ; Invasive Breast Carcinoma

Outcome Measures

Primary Outcomes (3)

• Determinants of inter-individual variation in afimoxifene drug concentrations in unradiated breast tissue related to skin histology, blood and lymph vessel density

  Univariate analyses will relate each characteristic to tissue drug concentration using either correlation analysis for continuous characteristics or a t-test, analysis of variance or rank sum test for categorical characteristics. Multiple linear regression modelling will be used to select those characteristics that provide the strongest independent contribution to the model.

  Up to 35 days post-treatment

• Determinants of inter-individual variation in afimoxifene drug concentrations in unradiated breast tissue related to the expression of xenobiotic transporters and enzymes

  Univariate analyses will relate each characteristic to tissue drug concentration using either correlation analysis for continuous characteristics or a t-test, analysis of variance or rank sum test for categorical characteristics. Multiple linear regression modelling will be used to select those characteristics that provide the strongest independent contribution to the model.

  Up to 35 days post-treatment

• Determinants of inter-individual variation in afimoxifene drug concentrations in unradiated breast tissue related to skin features

  Will be measured with confocal reflectance microscopy. Univariate analyses will relate each characteristic to tissue drug concentration using either correlation analysis for continuous characteristics or a t-test, analysis of variance or rank sum test for categorical characteristics. Multiple linear regression modelling will be used to select those characteristics that provide the strongest independent contribution to the model. A similar analysis will be conducted using the skin characteristics from the confocal reflectance microscopy.

  Up to 35 days pot-treatment

Secondary Outcomes (2)

• Effect of breast radiotherapy on drug concentrations resulting from transdermal delivery of afimoxifene (4-OHT)

  Up to 35 days post-treatment

• Differences between radiated and non-radiated skin and breast tissue that contribute to differences in permeation

  Up to 35 days post-treatment

Study Arms (1)

Treatment (afimoxifene)

EXPERIMENTAL

Patients apply afimoxifene gel topically QD to both breasts for 3 to 5 weeks and then undergo core needle biopsies of both breasts.

Drug: Afimoxifene; Procedure: Core Biopsy; Other: Questionnaire Administration

Interventions

Afimoxifene DRUG

Apply topically

Also known as: 4-Hydroxy-Tamoxifen, 4-hydroxytamoxifen, 4-OHT

Treatment (afimoxifene)

Core Biopsy PROCEDURE

Undergo core needle biopsy

Also known as: core needle biopsy

Treatment (afimoxifene)

Questionnaire Administration OTHER

Ancillary studies

Treatment (afimoxifene)

Eligibility Criteria

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

You may qualify if:

• Patients must have received prior unilateral breast radiotherapy (RT) for ductal breast carcinoma in situ (DCIS) or invasive cancer (\>= 12 weeks after the end of RT), and have an intact unradiated (non-RT) breast.
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 70%).
• A prior history of malignancy is allowed, as long as the patient is considered to have ?no evaluable disease? and cancer treatment has been completed.
• Females of child-bearing potential (FOCBP) and male partners of female participants must agree to use TWO effective forms of birth control (abstinence is not an allowed method) prior to study entry and for the duration of study participation, and for two 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. Should a female patient become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• NOTE: A FOCBP is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy
• Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for \> 12 months).
• FOCBP must have a negative urine pregnancy test within 7 days prior to registration on study.
• Willingness to avoid exposing breast skin to natural or artificial sunlight (i.e. tanning beds) for the duration of the study drug use.
• Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study.

You may not qualify if:

• Patients receiving any other investigational agents within 30 days of registration are not eligible.
• Patients currently using oral selective estrogen receptor modulators (SERMS) (tamoxifen, raloxifene, bazedoxifene) are not eligible.
• Note: Prior or current endocrine therapy other than SERMs are allowed.
• Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition afimoxifene (4-OHT) are not eligible.
• Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following, are not eligible:
• Hypertension that is not controlled on medication
• Ongoing or active infection requiring systemic treatment
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia
• Psychiatric illness/social situations that would limit compliance with study requirements
• Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient?s safety or study endpoints.
• Female patients who are pregnant or nursing are not eligible.
• Patients with prior bilateral breast cancer radiotherapy or radiotherapy for lymphoma will be excluded.
• Patients with skin lesions on the breast that disrupt the stratum corneum (e.g. eczema, ulceration) are not eligible.

Sponsors & Collaborators

• Northwestern University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Illinois Cancer Center

Chicago, Illinois, 60612, United States

Location

Related Publications (1)

• Lee O, Pilewskie M, Karlan S, Tull MB, Benante K, Xu Y, Blanco L, Helenowski I, Kocherginsky M, Yadav S, Hosseini O, Hansen N, Bethke K, Muzzio M, Troester MA, Dimond E, Perloff M, Heckman-Stoddard B, Khan SA. Local Transdermal Delivery of Telapristone Acetate Through Breast Skin, Compared With Oral Treatment: A Randomized Double-Blind, Placebo-Controlled Phase II Trial. Clin Pharmacol Ther. 2021 Mar;109(3):728-738. doi: 10.1002/cpt.2041. Epub 2020 Oct 25.

  PMID: 32996592 DERIVED

MeSH Terms

Conditions

Carcinoma, Intraductal, Noninfiltrating

Interventions

afimoxifene; 4,17 beta-dihydroxy-4-androstene-3-one; Biopsy, Needle; Biopsy, Large-Core Needle

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Breast Carcinoma In Situ; Carcinoma in Situ; Neoplasms, Ductal, Lobular, and Medullary

Intervention Hierarchy (Ancestors)

Biopsy; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Punctures; Investigative Techniques

Study Officials

• Seema A Khan, M.D.

  Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2019
• First Posted: July 5, 2019
• Study Start: February 17, 2020
• Primary Completion: January 31, 2026
• Study Completion (Estimated): June 25, 2026
• Last Updated: October 9, 2025

Record last verified: 2025-10

Locations

US (2)