(Z)-Endoxifen for the Treatment of Premenopausal Women With ER+/HER2- Breast Cancer

NCT ID: NCT05607004

Last Updated: 2025-10-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

87 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-02-14

Study Completion Date

2027-04-30

Brief Summary

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This open-label research study is studying (Z)-endoxifen as a possible treatment for pre-menopausal women with ER+/HER2- breast cancer. (Z)-endoxifen belongs to a group of drugs called selective estrogen receptor modulators or "SERM", which help block estrogen from attaching to cancer cells. This study has two parts: a pharmacokinetic part and a treatment part.

The PK part (how the body processes the drug) will enroll about 18 participants. All participants will take (Z)-endoxifen capsules daily. Twelve participants will be randomly assigned (50/50 chance) to take (Z)-endoxifen alone or (Z)-endoxifen with a monthly injection of goserelin a drug that temporarily stops the ovaries from making estrogen. This part will help determine the best dose of (Z)-endoxifen by measuring the drug levels in the blood and how long the body takes to remove it.

The Treatment Cohort has been simplified to a single study arm (Z)-endoxifen + goserelin. Up to 20 participants will be enrolled that have a baseline Ki-67 ≤ 10% and 45 participants will be enrolled that have a baseline Ki-67\>10%.

A key goal of the study is to see if (Z)-endoxifen can slow down or stop tumor growth as measured by a reduction in Ki-67 levels. Tumor tissue samples will be taken by breast biopsy after about 4 weeks of treatment to check levels of this biomarker. If the tumor shows signs of response, participants can continue treatment for up to 24 weeks or until they have surgery.

Study participation is up to 6 months (24 weeks of treatment) followed by surgery and a one-month follow up visit.

Detailed Description

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Conditions

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Breast Neoplasms Invasive Breast Cancer Estrogen-receptor-positive Breast Cancer HER2-negative Breast Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

This multicenter open-label study consists of two cohorts: PK and Treatment

The PK Cohort is a dose finding study to identify the dose to use in the Treatment Cohort.

The Treatment Cohort includes a single treatment arm. All participants will be assigned to (Z)-endoxifen + goserelin.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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PK Cohort

(Z)-endoxifen capsules orally once daily for 4 weeks. Initial (Z)-endoxifen dose evaluated will be 40 mg with an option to evaluate 20 mg or 80 mg.

The PK Cohort participants may extend treatment based on Ki-67% at Week 4.

If Ki-67 ≤ 10% at Week 4, participant will be offered option to continue on this treatment for up to 6 cycles/Week 24. Each cycle is 28 days.

If Ki-67 \> 10% at Week 4, participant will be withdrawn and go on to surgery.

Group Type EXPERIMENTAL

(Z)-endoxifen

Intervention Type DRUG

(Z)-endoxifen capsules. Doses of (Z)-endoxifen to be evaluated include 20 mg (two x 10 mg capsules), 40 mg (one 40 mg capsule) and 80 mg (two x 40 mg capsules).

Treatment Cohort - Single Treatment Arm

(Z)-endoxifen 40mg capsules orally once daily for 4 weeks + goserelin 3.6 mg by subcutaneous implant approximately every 28 days. (Z)-endoxifen 40mg dose based on results of PK Cohort.

If Ki-67 ≤ 10% at Week 4, continue on this treatment for up to 6 cycles/Week 24. Each cycle is 28 days. And then go on to surgery within 3 weeks of Cycle 6 day 26.

If Ki-67 \> 10% at Week 4, participant will complete early termination assessments.

Group Type EXPERIMENTAL

(Z)-endoxifen

Intervention Type DRUG

(Z)-endoxifen capsules. Doses of (Z)-endoxifen to be evaluated include 20 mg (two x 10 mg capsules), 40 mg (one 40 mg capsule) and 80 mg (two x 40 mg capsules).

goserelin

Intervention Type DRUG

goserelin 3.6 mg subcutaneous implant

PK Cohort 80 mg

(Z)-endoxifen 80 mg capsules orally once daily for 4 weeks.

The PK Cohort participants may extend treatment based on Ki-67% at Week 4.

If Ki-67 ≤ 10% at Week 4, participant will be offered option to continue on this treatment for up to 6 cycles/Week 24. Each cycle is 28 days.

If Ki-67 \> 10% at Week 4, participant will be withdrawn and go on to surgery.

Group Type EXPERIMENTAL

(Z)-endoxifen

Intervention Type DRUG

(Z)-endoxifen capsules. Doses of (Z)-endoxifen to be evaluated include 20 mg (two x 10 mg capsules), 40 mg (one 40 mg capsule) and 80 mg (two x 40 mg capsules).

PK Cohort 80 mg + OFS

(Z)-endoxifen 80 mg capsules orally once daily for 4 weeks + goserelin 3.6 mg by subcutaneous implant approximately every 28 days.

The PK Cohort participants may extend treatment based on Ki-67% at Week 4.

If Ki-67 ≤ 10% at Week 4, participant will be offered option to continue on this treatment for up to 6 cycles/Week 24. Each cycle is 28 days.

If Ki-67 \> 10% at Week 4, participant will be withdrawn and go on to surgery.

Group Type EXPERIMENTAL

(Z)-endoxifen

Intervention Type DRUG

(Z)-endoxifen capsules. Doses of (Z)-endoxifen to be evaluated include 20 mg (two x 10 mg capsules), 40 mg (one 40 mg capsule) and 80 mg (two x 40 mg capsules).

goserelin

Intervention Type DRUG

goserelin 3.6 mg subcutaneous implant

Interventions

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(Z)-endoxifen

(Z)-endoxifen capsules. Doses of (Z)-endoxifen to be evaluated include 20 mg (two x 10 mg capsules), 40 mg (one 40 mg capsule) and 80 mg (two x 40 mg capsules).

Intervention Type DRUG

goserelin

goserelin 3.6 mg subcutaneous implant

Intervention Type DRUG

Other Intervention Names

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endoxifen Zoladex

Eligibility Criteria

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Inclusion Criteria

1. Female sex assigned at birth. Female to male transgender individuals who have not had any hormonal therapy may be considered for the trial after review and approval from the medical monitor and study sponsor.
2. Age 18 years or older
3. Not lactating, pregnant, or planning to become pregnant in the next year and agrees to take adequate steps to prevent becoming pregnant beginning at informed consent, during treatment and for 9 months after last dose and agree to not breast feed during treatment and for 3 months after last dose.
4. Must agree to use at least one non-hormonal highly effective method of contraception for the entire duration of study participation beginning at informed consent. Highly effective methods of birth control are defined as those, alone or in combination, that resulted in a low failure rate of \<1% per year when used consistently and correctly such as intrauterine devices (IUDs, non-hormonal such as copper IUD), bilateral tubal occlusion, sexual abstinence or vasectomized partner
5. Premenopausal defined as any female who:

1. is menstruating or
2. is not menstruating (last menstrual period \> 3 months prior to registration) but has a plasma estradiol in the premenopausal range as assessed locally
6. Pathologic confirmation of strongly estrogen receptor positive (ER+) (defined as estrogen receptor \[ER\] ≥ 67% or Allred Score 6-8) by local institution protocol
7. Eastern Cooperative Oncology Group ECOG Performance Status (ECOG PS) of 0 to 2
8. Nottingham (Elston-Ellis) Grade 1 or 2
9. HER2- breast cancer (histologically confirmed) using American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines
10. Clinical T2 or T3 invasive breast cancer (per American Joint Committee on Cancer \[AJCC\] 8th edition clinical staging)
11. Clinical N0 or N1 invasive breast cancer (per American Joint Committee on Cancer \[AJCC\] 8th edition clinical staging)
12. MRI ≤ 35 days of registration
13. Must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects
14. Willing to provide blood and breast tissue samples for research purposes at specified timepoints for the duration of their participation in the trial.

Exclusion Criteria

1. Bilateral invasive breast cancer; Inflammatory breast cancer defined as clinically significant erythema of the breast and/or documented dermal lymphatic invasion or bilateral invasive breast cancer (patients with pre-malignant disease or DCIS/LCIS in contralateral breast are eligible)
2. Prior diagnosis or treatment for breast cancer, including carcinoma in situ, or history of any other active malignancy within the past 2 years prior to study entry with the exception of:

1. Adequately treated in situ carcinoma of the cervix uteri
2. Adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin
3. Any other malignancy with a life expectancy of less than 2 years
3. Any uncontrolled intercurrent illness including, but not limited to:

1. Ongoing or active infection requiring systemic treatment with strong inhibitors/inducers of CYP450 enzymes (including bacterial infection, fungal infection, or detectable viral infection).
2. Symptomatic congestive heart failure,
3. Unstable angina pectoris,
4. Uncontrolled symptomatic cardiac arrhythmias
5. Uncontrolled hypertension
6. Uncontrolled diabetes (Hemoglobin A1c \[HbA1c\] \>7%)
7. Marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval \> 470 milliseconds \[msec\]) using Fridericia's QT correction formula seen ≤ 28 days of registration
4. Any of the following co-morbid conditions:

1. Known cataracts or retinopathy
2. History of deep vein thrombosis (DVT)/pulmonary embolism (PE)
3. Known activated protein C (APC) resistance, an inherited coagulation disorder
4. End stage kidney disease requiring dialysis
5. Evidence of the following laboratory abnormalities ≤ 28 days prior to registration:

1. Total bilirubin ≥ 1.5 x upper limit of normal (ULN)
2. Aspartate aminotransferase (AST) or alanine amino transferase (ALT) ≥ 2.5 x ULN
3. Platelet count (PLT) ≤ 75,000/mm3
4. Hemoglobin (Hb) ≤ 10 g/dL
6. Hormonal therapies including birth control and hormone replacement therapy, or prior use of androgen-based therapy during the study or within 1 week of registration. If subject has a prior medical history of Depo-Provera®, it is recommended that the last dose of 3-month contraceptive agents are \> 2.5 months from registration.
7. Allergy to endoxifen, goserelin, or exemestane or any of their components
8. Participation in another investigational clinical trial ≤ 6 months of registration
9. Known metastatic disease
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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InClin

UNKNOWN

Sponsor Role collaborator

Atossa Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Matthew P Goetz, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

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Mayo Clinic Arizona

Phoenix, Arizona, United States

Site Status RECRUITING

University of Arizona

Tucson, Arizona, United States

Site Status RECRUITING

California Research Institute

Los Angeles, California, United States

Site Status RECRUITING

Mayo Clinic Florida

Jacksonville, Florida, United States

Site Status RECRUITING

Northwestern University

Chicago, Illinois, United States

Site Status RECRUITING

St. Elizabeth Healthcare

Edgewood, Kentucky, United States

Site Status RECRUITING

Henry Ford Cancer Institute

Detroit, Michigan, United States

Site Status RECRUITING

Mayo Clinic Rochester

Rochester, Minnesota, United States

Site Status RECRUITING

Washington University School of Medicine

St Louis, Missouri, United States

Site Status RECRUITING

Avera Cancer Institute

Sioux Falls, South Dakota, United States

Site Status RECRUITING

Vanderbilt Ingram Cancer Center

Nashville, Tennessee, United States

Site Status RECRUITING

Baylor University

Houston, Texas, United States

Site Status RECRUITING

Tranquility Research

Webster, Texas, United States

Site Status WITHDRAWN

Bon Secours Cancer Institute

Midlothian, Virginia, United States

Site Status RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Hayley Erickson

Role: CONTACT

206-486-1872

Other Identifiers

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ATOS-Z-201

Identifier Type: -

Identifier Source: org_study_id

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