Breast Carcinoma In SituPhase 1NCT03317405
Phase I Trial of Endoxifen Gel Versus Placebo in Women Undergoing Breast Surgery
A Phase 1 study testing Endoxifen Hydrochloride and Questionnaire Administration in people with Breast Carcinoma In Situ and Breast Ductal Carcinoma In Situ, run by National Cancer Institute (NCI) at 3 sites in United States.
Trial summary
This randomized phase I trial studies the side effects and best dose of endoxifen hydrochloride in treating participants who are undergoing breast surgery. Endoxifen hydrochloride may treat or reduce the risk of breast cancer. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Carcinoma In Situ, Breast Ductal Carcinoma In Situ, Breast Lobular Carcinoma In Situ
- What is being tested?
- Endoxifen Hydrochloride and Questionnaire Administration
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 3 sitesUnited States
- Study dates
- 31 Oct 2018to 12 Aug 2027
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Women scheduled for unilateral or bilateral mastectomy for breast cancer therapy, pathology confirmed stage 0-III (including ductal carcinoma in situ), or prophylaxis (BRCA1/2 mutation carriers, women with strong family history or lobular carcinoma in situ or other conditions where prophylactic mastectomy has been elected)
- Age >= 18 years (since breast cancer is not a pediatric disease and no safety data are available for ENX use in children)
- Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
- Total bilirubin < 1.5 x upper limit of normal (ULN) (in women with prior documented bilirubin elevations consistent with Gilbert's syndrome, total bilirubin up to 3 x ULN will be allowed)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) < 2.5 x ULN
- Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2.5 x ULN
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- Creatinine < 2 x ULN
- Alkaline phosphatase < 2.5 x ULN
- Blood urea nitrogen < 2 x ULN
- Ability to understand and the willingness to sign a written informed consent document which includes a requirement to apply study agent to sensitive body parts daily
- Willingness and ability to schedule mastectomy 21-28 days following start of study agent; women with breast implants may participate
- Willingness to avoid exposing breast skin to natural or artificial sunlight (i.e. tanning beds) for the duration of study agent dosing
- Negative urine or serum pregnancy test result, for participants of child bearing potential; female of child-bearing potential is any woman (regardless of sexual orientation, whether she has undergone a tubal ligation, or remains celibate by choice) who meets the following criteria: has not undergone a hysterectomy or bilateral oophorectomy; AND has had a menstrual period at any time in the preceding 12 consecutive months)
- The effects of topical ENX gel on the developing human fetus are unknown; for this reason, women of child-bearing potential and their male partners must agree to use effective forms of birth control (abstinence is not an allowed method) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
Who cannot join
- The presence of gross skin invasion/ulceration by the breast cancer, or inflammatory changes with skin edema AND erythema; Note: Paget's disease is permitted
- Women receiving a "nipple delay" procedure prior to mastectomy
- Women with skin diseases (psoriasis, eczema)
- A history of thromboembolic disorder
- Endometrial intraepithelial neoplasia (also known as atypical hyperplasia) or a high risk of uterine cancer, defined here as known carriers of Lynch syndrome mutations (MLH1, MSH2, MSH6, PMS2)
- Participants may not have received any other investigational agents in the previous 3 months
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- History of allergic reactions attributed to compounds of similar chemical or biologic composition to tamoxifen
- Taken tamoxifen or other selective estrogen/progesterone receptor modulators (SERMs/SPRMs) within two years prior to entering study or been required to discontinue SERM therapy due to thromboembolic or uterine toxicity
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- History of prior breast cancer-specific therapy within the previous 2 years (chemotherapy, radiation, anti-HER2 agents, endocrine agents, everolimus, CDK4-6 inhibitors); previous unilateral radiation of the contralateral side in women scheduled for mastectomy is allowed; study gel will be applied to both breasts
- History of prior mastectomy
- Pregnant or breastfeeding
- Patients receiving neoadjuvant chemotherapy with curative intent
- Men are excluded from this study since breast cancer is men is rare and there are no data regarding skin penetration of topical breast cancer prevention agents through male chest wall skin (which is thicker and harrier than female chest wall skin)
- Current users of other topical medications on the breast skin must be willing and able to discontinue use for the duration of participation; body lotion and other non-medicinal topical compounds may be applied > 4 hours after study gel application
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Northwestern University
Chicago, Illinois, 60611
Cedars-Sinai Medical Center
Los Angeles, California, 90048
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
About this study
Official title: Phase I Trial of Endoxifen Gel Versus Placebo Gel in Women Undergoing Breast Surgery
This randomized phase I trial studies the side effects and best dose of endoxifen hydrochloride in treating participants who are undergoing breast surgery. Endoxifen hydrochloride may treat or reduce the risk of breast cancer.
Read the detailed description
PRIMARY OBJECTIVE:
- To establish the dermal tolerability and safety of endoxifen hydrochloride (endoxifen [ENX]) gel administered topically to both breasts at two doses: 10 mg daily (5 mg per breast) and 20 mg daily (10 mg per breast) in comparison to vehicle placebo gel, using objective assessments based on Common Terminology Criteria for Adverse Events (CTCAE) criteria.
SECONDARY OBJECTIVES:
- To measure the breast tissue concentrations of (E) and (Z) isomers of N-desmethyl-4-hydroxytamoxifen (ENX) and 4-hydroxytamoxifen (4-OHT) at each dose (10 mg per day and 20 mg per day).
II. To measure the plasma concentrations of (E) and (Z) isomers ENX and 4-OHT at each dose (10 mg per day and 20 mg per day).
III. To measure serum estrogenic response to topical ENX gel therapy in comparison to vehicle placebo gel (sex hormone binding globulin and insulin-like growth factor [IGF] pathway proteins).
IV. To assess changes in coagulation parameters (factor VIII, factor IX, vWF, protein S) in response to ENX gel therapy in comparison to vehicle placebo gel.
- To assess symptoms related to use of endoxifen gel in comparison to vehicle placebo gel, as assessed by the Breast Cancer Prevention Trial (BCPT) Eight Symptom Scale (BESS) questionnaire.
EXPLORATORY OBJECTIVE:
- Using pathological lesion-matched pre- and post-therapy tissue samples, to explore the potential therapeutic effects of the two doses of ENX gel in comparison to vehicle placebo gel: a) by IHC, Ki67 labelling (for cell proliferation), estrogen receptor (ER), progesterone receptor (PR) expression (for estrogen blockade); b) by expression of a panel of genes reported to change with ENX exposure (using nanostring assays).
OUTLINE: Participants are randomized in Cohorts 1 and 2. All subjects in Cohort 3 will receive active agent.
COHORT I: Participants apply endoxifen hydrochloride gel to both breast skin and keep it untouched over at least 4 hours once daily for 21-28 days before breast surgery.
COHORT II: Participants apply placebo to both breast skin and keep it untouched over at least 4 hours once daily for 21-28 days before breast surgery.
COHORT III: Participants apply endoxifen hydrochloride gel to both breast skin and keep it untouched over at least 4 hours once daily for 21-28 days before breast surgery.
After completion of study treatment, participants are followed up at 60 days.
- Conditions
- Breast Carcinoma In Situ, Breast Ductal Carcinoma In Situ, Breast Lobular Carcinoma In Situ, Stage I Breast Cancer AJCC v7, Stage IA Breast Cancer AJCC v7, Stage IB Breast Cancer AJCC v7
- Being tested
- Endoxifen Hydrochloride, Placebo Administration, Questionnaire Administration
- Medical subject headings
- Breast Carcinoma In Situ, Carcinoma, Intraductal, Noninfiltrating, Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Endoxifen HydrochlorideDrug
Also called Z-Endoxifen HCl, Z-Endoxifen Hydrochloride
Apply to the skin
Placebo AdministrationOther
Apply to the skin
Questionnaire AdministrationOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Cohort I (endoxifen hydrochloride) | Experimental | Participants apply endoxifen hydrochloride gel to both breast skin and keep it untouched over at least 4 hours once daily for 21-28 days before breast surgery. Receives: Drug: Endoxifen Hydrochloride; Other: Questionnaire Administration |
| Cohort II (placebo) | Placebo comparator | Participants apply placebo to both breast skin and keep it untouched over at least 4 hours once daily for 21-28 days before breast surgery. Receives: Other: Placebo Administration; Other: Questionnaire Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dermal Toxicity on Breast Skin at the Application Site
Number of participants with dermal toxicity on breast skin at the transdermal gel application site. Will be assessed by Common Terminology Criteria for Adverse Events version 4.
Measured: Up to 60 days
Secondary outcomes (4)
Drug Concentration in Tissue
Concentrations of (E) and (Z) Isomers ENX in right and left breast tissue at end of intervention (up to 4 weeks) in tissue samples
Measured: up to 28 days
Drug Concentration in Plasma
Concentration of (E) and (Z) Isomers ENX in plasma at the end of intervention (up to 4 weeks)
Measured: baseline and up to 28 days
Change in Plasma Estrogenic and Coagulation Parameters
Change in plasma Estrogenic and Coagulation Parameters from baseline to end of intervention (up to 28 days) including: IGF1, IGFBP3, SHBG.
Measured: baseline and up to 28 days
Change in Pre-therapy and Post-therapy Symptoms Captured by BESS Questionnaire
Assessed using the Breast Cancer Prevention Trial (BCPT) Eight Symptom Scale (BESS) questionnaire. A patient reported outcome, subscale scores range from 0 (Not at All) to 4 (Extremely) when asked about experiencing symptoms. A positive change in scores indicates an increase in symptoms experienced and a negative change in scores indicates a decrease in symptoms experienced.
Measured: baseline and up to 60 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2017
- Study start31 Oct 2018
- Primary completion22 Feb 2021
- Study completion12 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast Carcinoma In SituStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Seema A Khan, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03317405
- Sponsor's protocol ID
- NCI-2017-01921
- Other IDs
- NCI-2017-01921, N01-CN-2012-00035, NCI2017-09-01, NWU2017-09-01, N01CN00035, P30CA060553
- Status last verified
- Aug 2026
- First submitted
- 20 Oct 2017
- Last updated
- 2 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial of Endoxifen Gel Versus Placebo Gel in Women Undergoing Breast Surgery
- ClinicalTrials.gov ID
- NCT03317405
- Acronym / sponsor ID
- NCI-2017-01921
- Conditions
- Breast Carcinoma In Situ, Breast Ductal Carcinoma In Situ, Breast Lobular Carcinoma In Situ, Stage I Breast Cancer AJCC v7, Stage IA Breast Cancer AJCC v7, Stage IB Breast Cancer AJCC v7
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 32 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 31 Oct 2018 (actual)
- Primary completion
- 22 Feb 2021 (actual)
- Study completion
- 12 Aug 2027 (estimated)
- First posted
- 23 Oct 2017 (actual)
- Results
- Posted 13 Jun 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This randomized phase I trial studies the side effects and best dose of endoxifen hydrochloride in treating participants who are undergoing breast surgery. Endoxifen hydrochloride may treat or reduce the risk of breast cancer.
Detailed description
PRIMARY OBJECTIVE:
- To establish the dermal tolerability and safety of endoxifen hydrochloride (endoxifen [ENX]) gel administered topically to both breasts at two doses: 10 mg daily (5 mg per breast) and 20 mg daily (10 mg per breast) in comparison to vehicle placebo gel, using objective assessments based on Common Terminology Criteria for Adverse Events (CTCAE) criteria.
SECONDARY OBJECTIVES:
- To measure the breast tissue concentrations of (E) and (Z) isomers of N-desmethyl-4-hydroxytamoxifen (ENX) and 4-hydroxytamoxifen (4-OHT) at each dose (10 mg per day and 20 mg per day).
II. To measure the plasma concentrations of (E) and (Z) isomers ENX and 4-OHT at each dose (10 mg per day and 20 mg per day).
III. To measure serum estrogenic response to topical ENX gel therapy in comparison to vehicle placebo gel (sex hormone binding globulin and insulin-like growth factor [IGF] pathway proteins).
IV. To assess changes in coagulation parameters (factor VIII, factor IX, vWF, protein S) in response to ENX gel therapy in comparison to vehicle placebo gel.
- To assess symptoms related to use of endoxifen gel in comparison to vehicle placebo gel, as assessed by the Breast Cancer Prevention Trial (BCPT) Eight Symptom Scale (BESS) questionnaire.
EXPLORATORY OBJECTIVE:
- Using pathological lesion-matched pre- and post-therapy tissue samples, to explore the potential therapeutic effects of the two doses of ENX gel in comparison to vehicle placebo gel: a) by IHC, Ki67 labelling (for cell proliferation), estrogen receptor (ER), progesterone receptor (PR) expression (for estrogen blockade); b) by expression of a panel of genes reported to change with ENX exposure (using nanostring assays).
OUTLINE: Participants are randomized in Cohorts 1 and 2. All subjects in Cohort 3 will receive active agent.
COHORT I: Participants apply endoxifen hydrochloride gel to both breast skin and keep it untouched over at least 4 hours once daily for 21-28 days before breast surgery.
COHORT II: Participants apply placebo to both breast skin and keep it untouched over at least 4 hours once daily for 21-28 days before breast surgery.
COHORT III: Participants apply endoxifen hydrochloride gel to both breast skin and keep it untouched over at least 4 hours once daily for 21-28 days before breast surgery.
After completion of study treatment, participants are followed up at 60 days.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort I (endoxifen hydrochloride) | Experimental | Drug: Endoxifen Hydrochloride, Other: Questionnaire AdministrationParticipants apply endoxifen hydrochloride gel to both breast skin and keep it untouched over at least 4 hours once daily for 21-28 days before breast surgery. |
| Cohort II (placebo) | Placebo comparator | Other: Placebo Administration, Other: Questionnaire AdministrationParticipants apply placebo to both breast skin and keep it untouched over at least 4 hours once daily for 21-28 days before breast surgery. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Women scheduled for unilateral or bilateral mastectomy for breast cancer therapy, pathology confirmed stage 0-III (including ductal carcinoma in situ), or prophylaxis (BRCA1/2 mutation carriers, women with strong family history or lobular carcinoma in situ or other conditions where prophylactic mastectomy has been elected)
- Age >= 18 years (since breast cancer is not a pediatric disease and no safety data are available for ENX use in children)
- Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
- Total bilirubin < 1.5 x upper limit of normal (ULN) (in women with prior documented bilirubin elevations consistent with Gilbert's syndrome, total bilirubin up to 3 x ULN will be allowed)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) < 2.5 x ULN
Key exclusion criteria (15 listed)
- The presence of gross skin invasion/ulceration by the breast cancer, or inflammatory changes with skin edema AND erythema; Note: Paget's disease is permitted
- Women receiving a "nipple delay" procedure prior to mastectomy
- Women with skin diseases (psoriasis, eczema)
- A history of thromboembolic disorder
- Endometrial intraepithelial neoplasia (also known as atypical hyperplasia) or a high risk of uterine cancer, defined here as known carriers of Lynch syndrome mutations (MLH1, MSH2, MSH6, PMS2)
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 |
|---|---|---|
| Endoxifen HydrochlorideAlso: Z-Endoxifen HCl, Z-Endoxifen HydrochlorideApply to the skin | Drug | Cohort I (endoxifen hydrochloride) |
| Placebo AdministrationApply to the skin | Other | Cohort II (placebo) |
| Questionnaire AdministrationAncillary studies | Other | Cohort I (endoxifen hydrochloride), Cohort II (placebo) |
Primary outcome
Number of Participants With Dermal Toxicity on Breast Skin at the Application Site
Time frame: Up to 60 days
Number of participants with dermal toxicity on breast skin at the transdermal gel application site. Will be assessed by Common Terminology Criteria for Adverse Events version 4.
4 secondary outcomes
Drug Concentration in Tissue
Time frame: up to 28 days
Drug Concentration in Plasma
Time frame: baseline and up to 28 days
Change in Plasma Estrogenic and Coagulation Parameters
Time frame: baseline and up to 28 days
Change in Pre-therapy and Post-therapy Symptoms Captured by BESS Questionnaire
Time frame: baseline and up to 60 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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 principal investigator
Northwestern University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Endoxifen Hydrochloride and Questionnaire Administration in people with Breast Carcinoma In Situ and Breast Ductal Carcinoma In Situ, run by National Cancer Institute (NCI) at 3 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 14 inclusion and 15 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 2 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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. Some participants in this study may receive a placebo. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Jun 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With Dermal Toxicity on Breast Skin at the Application Site (time frame: Up to 60 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Sep 2026.