Cancer SurvivorPhase 2NCT04009044
Topical Afimoxifene in Treating Patients With Breast Cancer Who Have Undergone Radiation Therapy on One Breast
A Phase 2 study testing Afimoxifene, Core Biopsy and Questionnaire Administration in people with Cancer Survivor and Ductal Breast Carcinoma In Situ, run by Northwestern University at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Cancer Survivor, Ductal Breast Carcinoma In Situ, Invasive Breast Carcinoma
- What is being tested?
- Afimoxifene, Core Biopsy and Questionnaire Administration
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 156 participants
- Where
- 2 sitesUnited States
- Study dates
- 17 Feb 2020to 25 Jun 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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.
- Patients with a history of endometrial neoplasia are not eligible.
- Patients with a history of thromboembolic disease are not eligible.
- Note: history of varicose veins and superficial phlebitis is allowed.
- Patients who are undergoing active treatment for any malignancy will be excluded.
- Male patients are excluded from this study since 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).
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Northwestern University
Chicago, Illinois, 60611
University of Illinois Cancer Center
Chicago, Illinois, 60612
About this study
Official title: A Phase II Study of the Determinants of Transdermal Drug Delivery to the Normal and the Radiated Breast
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.
Read the detailed description
PRIMARY OBJECTIVES:
- To identify the skin features that drive inter-individual variation in dermal drug permeation between individuals.
SECONDARY OBJECTIVES:
- To relate breast tissue drug concentration to skin histology, skin vascularity, skin transporter proteins, and skin features measured using confocal reflectance microscopy.
II. To assess the feasibility of transdermal drug delivery to the radiated breast.
OUTLINE:
Patients apply afimoxifene gel topically once daily (QD) to both breasts for 4 weeks and then undergo core needle biopsies of both breasts.
Patients receive follow up phone call 21-35 days after biopsy.
- Being tested
- Afimoxifene, Core Biopsy, Questionnaire Administration
- Medical subject headings
- Carcinoma, Intraductal, Noninfiltrating
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AfimoxifeneDrug
Also called 4-Hydroxy-Tamoxifen, 4-hydroxytamoxifen, 4-OHT
Apply topically
Core BiopsyProcedure or surgery
Also called core needle biopsy
Undergo core needle biopsy
Questionnaire AdministrationOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Afimoxifene; Procedure: Core Biopsy; Other: Questionnaire Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Up to 35 days pot-treatment
Secondary outcomes (2)
Effect of breast radiotherapy on drug concentrations resulting from transdermal delivery of afimoxifene (4-OHT)
Tissue drug concentrations will be compared between radiated and non-radiated breasts using a mixed linear model, with breast radiation status as a fixed effect of interest and person as a random effect. Analyses will also be done to compare the skin data (histology, immunohistochemistry [IHC], protein expression, CRS) between radiated and non-radiated breasts. While most characteristics will be continuous, other metrics will be analyzed by using different link functions in similarly constructed generalized linear model.
Measured: Up to 35 days post-treatment
Differences between radiated and non-radiated skin and breast tissue that contribute to differences in permeation
Tissue drug concentrations will be compared between radiated and non-radiated breasts using a mixed linear model, with breast radiation status as a fixed effect of interest and person as a random effect. Analyses will also be done to compare the skin data (histology, IHC, protein expression, CRS) between radiated and non-radiated breasts. While most characteristics will be continuous, other metrics will be analyzed by using different link functions in similarly constructed generalized linear model.
Measured: Up to 35 days post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jul 2019
- Study start17 Feb 2020
- Primary completion31 Jan 2026 (estimated)
- Study completion25 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cancer SurvivorStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 156 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Seema A Khan, M.D., Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04009044
- Sponsor's protocol ID
- NU 18B05
- Other IDs
- NCI-2019-03771, NU 18B05, P30CA060553
- Status last verified
- Oct 2025
- First submitted
- 2 Jul 2019
- Last updated
- 9 Oct 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 32996592
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of the Determinants of Transdermal Drug Delivery to the Normal and the Radiated Breast
- ClinicalTrials.gov ID
- NCT04009044
- Acronym / sponsor ID
- NU 18B05
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 156 participants (estimated)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 17 Feb 2020 (actual)
- Primary completion
- 31 Jan 2026 (estimated)
- Study completion
- 25 Jun 2026 (estimated)
- First posted
- 5 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVES:
- To identify the skin features that drive inter-individual variation in dermal drug permeation between individuals.
SECONDARY OBJECTIVES:
- To relate breast tissue drug concentration to skin histology, skin vascularity, skin transporter proteins, and skin features measured using confocal reflectance microscopy.
II. To assess the feasibility of transdermal drug delivery to the radiated breast.
OUTLINE:
Patients apply afimoxifene gel topically once daily (QD) to both breasts for 4 weeks and then undergo core needle biopsies of both breasts.
Patients receive follow up phone call 21-35 days after biopsy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (afimoxifene) | Experimental | Drug: Afimoxifene, Procedure: Core Biopsy, Other: Questionnaire AdministrationPatients apply afimoxifene gel topically QD to both breasts for 3 to 5 weeks and then undergo core needle biopsies of both breasts. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
- FOCBP must have a negative urine pregnancy test within 7 days prior to registration on study.
Key exclusion criteria (20 listed)
- 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.
- 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:
- Female patients who are pregnant or nursing are not eligible.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AfimoxifeneAlso: 4-Hydroxy-Tamoxifen, 4-hydroxytamoxifen, 4-OHTApply topically | Drug | Treatment (afimoxifene) |
| Core BiopsyAlso: core needle biopsyUndergo core needle biopsy | Procedure or surgery | Treatment (afimoxifene) |
| Questionnaire AdministrationAncillary studies | Other | Treatment (afimoxifene) |
Primary outcome
Determinants of inter-individual variation in afimoxifene drug concentrations in unradiated breast tissue related to skin histology, blood and lymph vessel density
Time frame: Up to 35 days post-treatment
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.
Determinants of inter-individual variation in afimoxifene drug concentrations in unradiated breast tissue related to the expression of xenobiotic transporters and enzymes
Time frame: Up to 35 days post-treatment
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.
Determinants of inter-individual variation in afimoxifene drug concentrations in unradiated breast tissue related to skin features
Time frame: Up to 35 days pot-treatment
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.
2 secondary outcomes
Effect of breast radiotherapy on drug concentrations resulting from transdermal delivery of afimoxifene (4-OHT)
Time frame: Up to 35 days post-treatment
Differences between radiated and non-radiated skin and breast tissue that contribute to differences in permeation
Time frame: Up to 35 days post-treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2025.
- Derived from this study: PubMed 32996592Lee 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Seema A Khan, M.D. principal investigator
Northwestern University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Afimoxifene, Core Biopsy and Questionnaire Administration in people with Cancer Survivor and Ductal Breast Carcinoma In Situ, run by Northwestern University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 9 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determinants of inter-individual variation in afimoxifene drug concentrations in unradiated breast tissue related to skin histology, blood and lymph vessel density (time frame: Up to 35 days post-treatment). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04009044, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2025.