Breast NeoplasmsPhase 2EVANGELINENCT05607004
(Z)-Endoxifen for the Treatment of Premenopausal Women With ER+/HER2- Breast Cancer
A Phase 2 study testing (Z)-endoxifen and goserelin in people with Breast Neoplasms and Invasive Breast Cancer, run by Atossa Therapeutics, Inc. at 14 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Neoplasms, Invasive Breast Cancer, Estrogen-receptor-positive Breast Cancer
- What is being tested?
- (Z)-endoxifen and goserelin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 87 participants
- Where
- 14 sitesUnited States
- Study dates
- 14 Feb 2023to Apr 2027
- 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
- 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.
- Age 18 years or older
- 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.
- 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
- Premenopausal defined as any female who:
- is menstruating or
Show all 16Show fewer
- is not menstruating (last menstrual period > 3 months prior to registration) but has a plasma estradiol in the premenopausal range as assessed locally
- Pathologic confirmation of strongly estrogen receptor positive (ER+) (defined as estrogen receptor [ER] ≥ 67% or Allred Score 6-8) by local institution protocol
- Eastern Cooperative Oncology Group ECOG Performance Status (ECOG PS) of 0 to 2
- Nottingham (Elston-Ellis) Grade 1 or 2
- HER2- breast cancer (histologically confirmed) using American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines
- Clinical T2 or T3 invasive breast cancer (per American Joint Committee on Cancer [AJCC] 8th edition clinical staging)
- Clinical N0 or N1 invasive breast cancer (per American Joint Committee on Cancer [AJCC] 8th edition clinical staging)
- MRI ≤ 35 days of registration
- 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
- Willing to provide blood and breast tissue samples for research purposes at specified timepoints for the duration of their participation in the trial.
Who cannot join
- 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)
- 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:
- Adequately treated in situ carcinoma of the cervix uteri
- Adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin
- Any other malignancy with a life expectancy of less than 2 years
- Any uncontrolled intercurrent illness including, but not limited to:
Show all 27Show fewer
- Ongoing or active infection requiring systemic treatment with strong inhibitors/inducers of CYP450 enzymes (including bacterial infection, fungal infection, or detectable viral infection).
- Symptomatic congestive heart failure,
- Unstable angina pectoris,
- Uncontrolled symptomatic cardiac arrhythmias
- Uncontrolled hypertension
- Uncontrolled diabetes (Hemoglobin A1c [HbA1c] >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
- Any of the following co-morbid conditions:
- Known cataracts or retinopathy
- History of deep vein thrombosis (DVT)/pulmonary embolism (PE)
- Known activated protein C (APC) resistance, an inherited coagulation disorder
- End stage kidney disease requiring dialysis
- Evidence of the following laboratory abnormalities ≤ 28 days prior to registration:
- Total bilirubin ≥ 1.5 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST) or alanine amino transferase (ALT) ≥ 2.5 x ULN
- Platelet count (PLT) ≤ 75,000/mm3
- Hemoglobin (Hb) ≤ 10 g/dL
- 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.
- Allergy to endoxifen, goserelin, or exemestane or any of their components
- Participation in another investigational clinical trial ≤ 6 months of registration
- Known metastatic disease
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
United States14 sites
Northwestern University
Chicago, Illinois, 60611
Henry Ford Cancer Institute
Detroit, Michigan, 48202
St. Elizabeth Healthcare
Edgewood, Kentucky, 41017
Baylor University
Houston, Texas, 77054
Mayo Clinic Florida
Jacksonville, Florida, 32224
California Research Institute
Los Angeles, California, 90027
Bon Secours Cancer Institute
Midlothian, Virginia, 23114
Vanderbilt Ingram Cancer Center
Nashville, Tennessee, 37204
Mayo Clinic Arizona
Phoenix, Arizona, 85054
Mayo Clinic Rochester
Rochester, Minnesota, 55905
Fred Hutchinson Cancer Center
Seattle, Washington, 98109
Avera Cancer Institute
Sioux Falls, South Dakota, 57105
Washington University School of Medicine
St Louis, Missouri, 63110
University of Arizona
Tucson, Arizona, 85719
About this study
Official title: A Phase 2 Trial of (Z)-Endoxifen + Goserelin as Neoadjuvant Treatment for Premenopausal Women With ER+, HER2-, Breast Cancer
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.
Read more
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.
- Conditions
- Breast Neoplasms, Invasive Breast Cancer, Estrogen-receptor-positive Breast Cancer, HER2-negative Breast Cancer
- Being tested
- (Z)-endoxifen, goserelin
- Keywords
- breast cancer, ER+/HER2-, endocrine therapy, neoadjuvant, (Z)-endoxifen, exemestane, goserelin, Ki-67, estrogen receptor negative, human epidermal growth factor receptor 2 negative, Stage II, tamoxifen, PKCB1
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
(Z)-endoxifenDrug
Also called 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).
goserelinDrug
Also called Zoladex
goserelin 3.6 mg subcutaneous implant
| Study group | Role | What they receive |
|---|---|---|
| PK Cohort | Experimental | (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. Receives: Drug: (Z)-endoxifen |
| Treatment Cohort - Single Treatment Arm | Experimental | (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. Receives: Drug: (Z)-endoxifen; Drug: goserelin |
| PK Cohort 80 mg | Experimental | (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. Receives: Drug: (Z)-endoxifen |
| PK Cohort 80 mg + OFS | Experimental | (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. Receives: Drug: (Z)-endoxifen; Drug: goserelin |
What is being measured
The primary outcome is the main question the study is designed to answer.
PK Cohort - (Z)-endoxifen steady-state plasma concentrations
(Z)-endoxifen steady-state plasma concentrations (Css) of evaluable subjects who completed at least one cycle of treatment (28 +/- 3 days)
Measured: After 4 weeks of treatment
For Analysis of Cohort A (Treatment Cohort): determine whether the week 4 Ki-67≤10% rate is at least 65%
For analysis Cohort A (subjects that have a baseline Ki-67>10%): the primary objective is to determine whether the Week 4 Ki-67 ≤ 10% rate is at least 65% among premenopausal women with primary estrogen receptor positive (ER+), Human Epidermal Growth Factor Receptor 2 negative (HER2-) breast cancer.
Measured: After 4 weeks of treatment
For analysis Cohort B (Treatment Cohort): determine the objective tumor response rate at 24 weeks
For analysis Cohort B (subjects have baseline Ki-67≤ 10%): the primary objective is to determine the objective tumor response rate at 24 weeks among premenopausal women with ER+, HER2-, Ki-67 ≤ 10% breast cancer receiving (Z) endoxifen plus goserelin.
Measured: After 24 weeks of treatment
Secondary outcomes (26)
PK Cohort - Area under the plasma (Z)-endoxifen concentration-time curve from time zero to last measurable concentration
Area under the plasma (Z)-endoxifen concentration-time curve from time zero to last measurable concentration (AUC0-24) on Days 1 and 28 of evaluable subjects who completed at least one cycle of treatment (28 +/- 3 days)
Measured: Days 1 and 28
PK Cohort - Area under the plasma (E)-endoxifen concentration-time curve from time zero to last measurable concentration
Area under the plasma (E)-endoxifen concentration-time curve from time zero to last measurable concentration (AUC0-24) on Days 1 and 28 of evaluable subjects who completed at least one cycle of treatment (28 +/- 3 days)
Measured: Days 1 and 28
PK Cohort - Accumulation and accumulation half-life
Accumulation and accumulation half-life (Day 28 AUC0-24/Day 1 AUC0-24) of evaluable subjects who completed at least one cycle of treatment (28 +/- 3 days)
Measured: Days 1 and 28
PK Cohort - (Z)-endoxifen steady-state clearance
(Z)-endoxifen CLss (steady-state clearance) of evaluable subjects who completed at least one cycle of treatment (28 +/- 3 days)
Measured: up to 28 days
PK Cohort - (E)-endoxifen steady-state clearance
(E)-endoxifen CLss (steady-state clearance) of evaluable subjects who completed at least one cycle of treatment (28 +/- 3 days)
Measured: up to 28 days
PK Cohort - Maximum plasma (Z)-endoxifen concentration
Maximum plasma (Z)-endoxifen concentration (Cmax) of evaluable subjects who completed at least one cycle of treatment (28 +/- 3 days)
Measured: up to 28 days
PK Cohort - Maximum plasma (E)-endoxifen concentration
Maximum plasma (E)-endoxifen concentration (Cmax) of evaluable subjects who completed at least one cycle of treatment (28 +/- 3 days)
Measured: up to 28 days
PK Cohort - Time to plasma (Z)-endoxifen maximum concentration
Time to plasma (Z)-endoxifen maximum concentration (Tmax) of evaluable subjects who completed at least one cycle of treatment (28 +/- 3 days)
Measured: up to 28 days
PK Cohort - Time to plasma (E)-endoxifen maximum concentration
Time to plasma (E)-endoxifen maximum concentration (Tmax) of evaluable subjects who completed at least one cycle of treatment (28 +/- 3 days)
Measured: up to 28 days
PK Cohort - plasma (Z)-endoxifen concentration
Trough concentrations of (Z)-endoxifen for subjects in the Treatment Extension
Measured: Day 1 up to 12 weeks and up to end of treatment or up to 24 weeks.
PK Cohort - plasma (E)-endoxifen concentration
Trough concentrations of (Z)-endoxifen for subjects in the Treatment Extension
Measured: Day 1 up to 12 weeks and up to end of treatment or up to 24 weeks.
PK Cohort- Endocrine sensitive disease rate based on Ki-67 percent after 4 weeks of treatment
Endocrine sensitive disease rate will be estimated as the percentage of subjects whose 4-week tumor biopsy finds Ki-67 less than or equal to 10 percent among evaluable subjects who began protocol treatment
Measured: After 4 weeks of treatment
All Cohorts - Incidence and severity of adverse events per CTCAE by treatment
Incidence and severity of adverse events per CTCAE
Measured: Informed consent up to follow up visit or up to 30 weeks
All Cohorts - Incidence of Serious Adverse Events assessed by CTCAE version 5.0
Serious adverse events and adverse events leading to discontinuation of neoadjuvant treatment
Measured: Informed consent up to follow up visit or up to 30 weeks
All Cohorts - Incidence of Dose Reductions
The incidence of dose reductions
Measured: Informed consent up to end of treatment or up to 24 weeks
All Cohorts - Change in estradiol and estrone
Percent change from baseline in E1 and E2 at 4 weeks, and 24 weeks
Measured: Day 1, up to 4 weeks and up to end of treatment or up to 24 weeks.
All Cohorts - Percentage of subjects whose serum thymidine kinase 1 (TK1) is not detectable at 4 weeks and 24 weeks.
Percent of subjects whose serum TK1 is not detectable at 4 weeks and 24 weeks
Measured: Day 1, up to 4 weeks and up to end of treatment or up to 24 weeks.
Treatment Cohorts - Assess additional PK parameters of (Z)-endoxifen and (E)-endoxifen
Tissue and plasma (Z)-endoxifen and (E)-endoxifen concentrations at 4 weeks and 24 weeks
Measured: Day 1, up to 4 weeks, up to 12 weeks and up to 24 weeks
Treatment Cohorts - Radiographic Response Rate in the breast
Radiographic response rate in the breast at 4, 12, and 24 weeks as assessed by RECIST 1.1 criteria
Measured: Baseline Assessment, up to 4 weeks, up to 12 weeks, and up to 24 weeks
Treatment Cohorts - Pathologic Complete Response per American Joint Committee on Cancer staging system at time of surgery
Pathologic Complete Response (pCR) at surgery defined as the absence of residual invasive breast cancer on hematoxylin and eosin evaluation of the resected breast specimen and of all sampled lymph nodes (sentinel ± axillary) removed following completion of neoadjuvant systemic therapy
Measured: At time of surgery or up to 27 weeks
Treatment Cohorts - Pre-Operative Endocrine Prognostic Index at time of surgery
Rate of Pre-Operative Endocrine Prognostic Index (PEPI) 0 at time of surgery using residual tumor specimen
Measured: At time of surgery or up to 27 weeks
Treatment Cohorts - Residual Cancer Burden at time of surgery
Rate of residual cancer burden class of 0-I at time of surgery
Measured: At time of surgery or up to 27 weeks
Treatment Cohorts - Conversion Rate
Evaluate the conversion rate from breast conservation surgery ineligible to breast conservation surgery eligible. Evaluation is based on surgeon's impression of the type of surgery participant is eligible for (candidate for lumpectomy, candidate for modified radical mastectomy, inoperable) at baseline compared to surgeon's impression after completion of neoadjuvant treatment
Measured: From baseline to time of surgery or up to 27 weeks
Treatment Cohorts - Actual Conversion Rate
Evaluate the actual rate of breast conservation surgery. Evaluation will be based on the extent of the surgical procedure at the time of surgery (lumpectomy, partial or segmental mastectomy, simple/total mastectomy, skin and/or nipple sparing mastectomy, radical mastectomy or other)
Measured: At time of surgery or up to 27 weeks
Treatment Cohorts - Change in menopause quality of life (MENQOL)
Evaluate changes in menopause symptoms after neoadjuvant treatment
Measured: baseline, up to 4 weeks, and up to 24 weeks
Treatment Cohorts - Nodal response rate
Rate of nodal pCR in subjects with biopsy proven nodal disease
Measured: At time of surgery or up to 27 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2022
- Study start14 Feb 2023
- Primary completionNov 2026 (estimated)
- Study completionApr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast NeoplasmsStudies of the same condition, open and under way.
- 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
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 87 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Atossa Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- InClin, Inc.
- Responsible party
- Sponsor
- Investigators
- Matthew P Goetz, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05607004
- Sponsor's protocol ID
- ATOS-Z-201
- Acronym
- EVANGELINE
- Status last verified
- Jul 2026
- First submitted
- 26 Oct 2022
- Last updated
- 8 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Trial of (Z)-Endoxifen + Goserelin as Neoadjuvant Treatment for Premenopausal Women With ER+, HER2-, Breast Cancer
- ClinicalTrials.gov ID
- NCT05607004
- Acronym / sponsor ID
- EVANGELINE / ATOS-Z-201
- Conditions
- Breast Neoplasms, Invasive Breast Cancer, Estrogen-receptor-positive Breast Cancer, HER2-negative Breast Cancer
- Keywords
- breast cancer, ER+/HER2-, endocrine therapy, neoadjuvant, (Z)-endoxifen, exemestane, goserelin, Ki-67
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 87 participants (estimated)
- Lead sponsor
- Atossa Therapeutics, Inc.Industry (pharma, biotech, devices)
- Collaborators
- InClin, Inc.
- Study start
- 14 Feb 2023 (actual)
- Primary completion
- Nov 2026 (estimated)
- Study completion
- Apr 2027 (estimated)
- First posted
- 7 Nov 2022 (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 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| PK Cohort | Experimental | Drug: (Z)-endoxifen(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. |
| Treatment Cohort - Single Treatment Arm | Experimental | Drug: (Z)-endoxifen, Drug: goserelin(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. |
| PK Cohort 80 mg | Experimental | Drug: (Z)-endoxifen(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. |
| PK Cohort 80 mg + OFS | Experimental | Drug: (Z)-endoxifen, Drug: goserelin(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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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.
- Age 18 years or older
- 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.
- 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
- Premenopausal defined as any female who:
Key exclusion criteria (27 listed)
- 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)
- 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:
- Any uncontrolled intercurrent illness including, but not limited to:
- Any of the following co-morbid conditions:
- Evidence of the following laboratory abnormalities ≤ 28 days prior to registration:
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 |
|---|---|---|
| (Z)-endoxifenAlso: 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). | Drug | PK Cohort, PK Cohort 80 mg, PK Cohort 80 mg + OFS, Treatment Cohort - Single Treatment Arm |
| goserelinAlso: Zoladexgoserelin 3.6 mg subcutaneous implant | Drug | PK Cohort 80 mg + OFS, Treatment Cohort - Single Treatment Arm |
Primary outcome
PK Cohort - (Z)-endoxifen steady-state plasma concentrations
Time frame: After 4 weeks of treatment
(Z)-endoxifen steady-state plasma concentrations (Css) of evaluable subjects who completed at least one cycle of treatment (28 +/- 3 days)
For Analysis of Cohort A (Treatment Cohort): determine whether the week 4 Ki-67≤10% rate is at least 65%
Time frame: After 4 weeks of treatment
For analysis Cohort A (subjects that have a baseline Ki-67>10%): the primary objective is to determine whether the Week 4 Ki-67 ≤ 10% rate is at least 65% among premenopausal women with primary estrogen receptor positive (ER+), Human Epidermal Growth Factor Receptor 2 negative (HER2-) breast cancer.
For analysis Cohort B (Treatment Cohort): determine the objective tumor response rate at 24 weeks
Time frame: After 24 weeks of treatment
For analysis Cohort B (subjects have baseline Ki-67≤ 10%): the primary objective is to determine the objective tumor response rate at 24 weeks among premenopausal women with ER+, HER2-, Ki-67 ≤ 10% breast cancer receiving (Z) endoxifen plus goserelin.
26 secondary outcomes
PK Cohort - Area under the plasma (Z)-endoxifen concentration-time curve from time zero to last measurable concentration
Time frame: Days 1 and 28
PK Cohort - Area under the plasma (E)-endoxifen concentration-time curve from time zero to last measurable concentration
Time frame: Days 1 and 28
PK Cohort - Accumulation and accumulation half-life
Time frame: Days 1 and 28
PK Cohort - (Z)-endoxifen steady-state clearance
Time frame: up to 28 days
PK Cohort - (E)-endoxifen steady-state clearance
Time frame: up to 28 days
PK Cohort - Maximum plasma (Z)-endoxifen concentration
Time frame: up to 28 days
PK Cohort - Maximum plasma (E)-endoxifen concentration
Time frame: up to 28 days
PK Cohort - Time to plasma (Z)-endoxifen maximum concentration
Time frame: up to 28 days
PK Cohort - Time to plasma (E)-endoxifen maximum concentration
Time frame: up to 28 days
PK Cohort - plasma (Z)-endoxifen concentration
Time frame: Day 1 up to 12 weeks and up to end of treatment or up to 24 weeks.
PK Cohort - plasma (E)-endoxifen concentration
Time frame: Day 1 up to 12 weeks and up to end of treatment or up to 24 weeks.
PK Cohort- Endocrine sensitive disease rate based on Ki-67 percent after 4 weeks of treatment
Time frame: After 4 weeks of treatment
All Cohorts - Incidence and severity of adverse events per CTCAE by treatment
Time frame: Informed consent up to follow up visit or up to 30 weeks
All Cohorts - Incidence of Serious Adverse Events assessed by CTCAE version 5.0
Time frame: Informed consent up to follow up visit or up to 30 weeks
All Cohorts - Incidence of Dose Reductions
Time frame: Informed consent up to end of treatment or up to 24 weeks
All Cohorts - Change in estradiol and estrone
Time frame: Day 1, up to 4 weeks and up to end of treatment or up to 24 weeks.
All Cohorts - Percentage of subjects whose serum thymidine kinase 1 (TK1) is not detectable at 4 weeks and 24 weeks.
Time frame: Day 1, up to 4 weeks and up to end of treatment or up to 24 weeks.
Treatment Cohorts - Assess additional PK parameters of (Z)-endoxifen and (E)-endoxifen
Time frame: Day 1, up to 4 weeks, up to 12 weeks and up to 24 weeks
Treatment Cohorts - Radiographic Response Rate in the breast
Time frame: Baseline Assessment, up to 4 weeks, up to 12 weeks, and up to 24 weeks
Treatment Cohorts - Pathologic Complete Response per American Joint Committee on Cancer staging system at time of surgery
Time frame: At time of surgery or up to 27 weeks
Treatment Cohorts - Pre-Operative Endocrine Prognostic Index at time of surgery
Time frame: At time of surgery or up to 27 weeks
Treatment Cohorts - Residual Cancer Burden at time of surgery
Time frame: At time of surgery or up to 27 weeks
Treatment Cohorts - Conversion Rate
Time frame: From baseline to time of surgery or up to 27 weeks
Treatment Cohorts - Actual Conversion Rate
Time frame: At time of surgery or up to 27 weeks
Treatment Cohorts - Change in menopause quality of life (MENQOL)
Time frame: baseline, up to 4 weeks, and up to 24 weeks
Treatment Cohorts - Nodal response rate
Time frame: At time of surgery or up to 27 weeks
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 8 Jul 2026.
- Individual participant dataSharing planned: No
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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.
Matthew P Goetz, MD principal investigator
Mayo Clinic
14 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 (Z)-endoxifen and goserelin in people with Breast Neoplasms and Invasive Breast Cancer, run by Atossa Therapeutics, Inc. at 14 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 16 inclusion and 27 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 8 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 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?
PK Cohort - (Z)-endoxifen steady-state plasma concentrations (time frame: After 4 weeks of 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?
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 8 Jul 2026.