NCT03317405

Brief 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.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
32

participants targeted

Target at P50-P75 for phase_1

Timeline
3mo left

Started Oct 2018

Longer than P75 for phase_1

Geographic Reach
1 country

3 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress97%
Oct 2018Aug 2026

First Submitted

Initial submission to the registry

October 20, 2017

Completed
3 days until next milestone

First Posted

Study publicly available on registry

October 23, 2017

Completed
1 year until next milestone

Study Start

First participant enrolled

October 31, 2018

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 22, 2021

Completed
2.3 years until next milestone

Results Posted

Study results publicly available

June 13, 2023

Completed
3.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

August 12, 2026

Expected
Last Updated

May 4, 2026

Status Verified

February 1, 2026

Enrollment Period

2.3 years

First QC Date

October 20, 2017

Results QC Date

January 31, 2023

Last Update Submit

May 1, 2026

Conditions

Outcome Measures

Primary Outcomes (1)

  • 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.

    Up to 60 days

Secondary Outcomes (4)

  • Drug Concentration in Tissue

    up to 28 days

  • Drug Concentration in Plasma

    baseline and up to 28 days

  • Change in Plasma Estrogenic and Coagulation Parameters

    baseline and up to 28 days

  • Change in Pre-therapy and Post-therapy Symptoms Captured by BESS Questionnaire

    baseline and up to 60 days

Study Arms (2)

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.

Drug: Endoxifen HydrochlorideOther: 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.

Other: Placebo AdministrationOther: Questionnaire Administration

Interventions

Apply to the skin

Also known as: Z-Endoxifen HCl, Z-Endoxifen Hydrochloride
Cohort I (endoxifen hydrochloride)

Apply to the skin

Cohort II (placebo)

Ancillary studies

Cohort I (endoxifen hydrochloride)Cohort II (placebo)

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • 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

You may not qualify if:

  • 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
  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Breast Carcinoma In SituCarcinoma, Intraductal, NoninfiltratingBreast Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma in SituCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsNeoplasms by SiteBreast DiseasesSkin DiseasesSkin and Connective Tissue DiseasesAdenocarcinomaNeoplasms, Ductal, Lobular, and Medullary

Results Point of Contact

Title
Seema A. Khan
Organization
Northwestern University

Study Officials

  • Seema A Khan

    Northwestern University

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
LTE60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 20, 2017

First Posted

October 23, 2017

Study Start

October 31, 2018

Primary Completion

February 22, 2021

Study Completion (Estimated)

August 12, 2026

Last Updated

May 4, 2026

Results First Posted

June 13, 2023

Record last verified: 2026-02

Locations