Clinical trials are carefully designed research studies to determine whether new drugs or treatments work to control or cure a disease, symptom, side effect or improve quality of life.

The sponsor of this clinical trial is Atossa Therapeutics.  Atossa is a biopharmaceutical company headquartered in Seattle, Washington, whose mission is to develop innovative medicines in areas of significant unmet medical needs in oncology with a focus on breast cancer. 

(Z)-endoxifen is an investigational drug, meaning it has not been approved by the FDA. (Z)-endoxifen belongs to a class of drugs called selective estrogen receptor modulators (SERMs).  SERMs are a type of hormonal therapy medicine used to treat estrogen receptor-positive (ER+) breast cancer. 

SERMs block your body’s natural estrogen from binding with cancer cells in the breast. By cutting off the supply of estrogen, SERMs can stop ER+ cancer from growing and spreading in some patients.  In addition, there is evidence that (Z)-endoxifen may have additional anti-cancer properties through other mechanisms.

In premenopausal women, or those who still have periods, adequately treating ER+ breast cancer often includes additional medications that further cut off the supply of estrogen produced by functioning ovaries (also known as ovarian function suppression or OFS). It is thought that (Z)-endoxifen may be a strong enough anti-estrogen to be taken on its own without the need for additional medications. In the EVANGELINE study, we will check these things and compare to see if the safety and anti-cancer benefits of (Z)-endoxifen are different from those in patients taking standard treatments (goserelin and exemestane).

It is thought that (Z)-endoxifen may be a strong enough anti-estrogen to be taken on its own without the need for additional medications.  In the EVANGELINE study, we will check these things and compare to see if the safety and anti-cancer benefits of (Z)-endoxifen are different from those in patients taking standard treatments (goserelin and exemestane).  

This is an open-label, randomized, Phase 2 pre-surgical (also called neoadjuvant) study in premenopausal women 18 years of age and older with newly diagnosed early-stage ER+/HER2- breast cancer. Participants will receive endocrine treatment for up to 24 weeks and then have surgery.  The primary goal of the study is to: 

1) Part 1 - (Completed) Find a dose of (Z)-endoxifen that reaches certain levels in the blood that researchers have shown produce enhanced anti-cancer benefits.  This dose will be used in Part 2 of the study.   

In Part 1, patients were treated with (Z)-endoxifen, either alone or with Ovarian Function Suppression (OFS), to determine the dosing regimen for Part 2. A total of 22 patients received (Z)-endoxifen, with or without OFS. The comprehensive analysis of the data from Part 1 was used to select the appropriate dosing amount for Part 2. 

2) Part 2 - see if (Z)-endoxifen is just as effective at decreasing cancer cell growth compared to a standard treatment. In this treatment portion of the study (Part 2) about 190 people will participate.  There are two parts (2a and 2b):

Part 2a will enroll about 160 participants who will be randomly assigned to one of two groups (50/50 like a flip of a coin) to receive (Z)-endoxifen once daily by mouth or the current standard of care, which is exemestane (also called an aromatase inhibitor) once daily by mouth + one injection of goserelin about every 28 days. You and your doctor will know which treatment you receive (open-label). Part 2b will enroll about 30 participants who will take daily (Z)-endoxifen alone without goserelin.

You will be closely monitored for safety (with blood draws, tests, and interviews) and disease progression (by MRIs). Biopsies will be taken from your tumor at the start of treatment and after 4 weeks of treatment. Biopsies will help your doctor decide if your cancer is sensitive to treatment by measuring Ki-67, a commonly studied marker of breast cancer cell growth. 

If after 4 weeks of treatment, your biopsy shows the treatment is not working for you, your doctor may offer to modify your treatment. Once treatment is complete, approximately 24 weeks, you will go on to have surgery.  If you respond to treatment, your surgery may be less invasive.

Additional information can be obtained from the national clinical study register, Clinicaltrials.gov. (click here NCT05607004).

There are no placebos in this study.

Everyone will receive treatment for their breast cancer, and both you and your doctor will know which treatment you are assigned to (open-label).  

In Part 2 you will be assigned to Part 2a or Part 2b based on your diagnostic Ki-67 value. For those with a Ki-67 value > 10%, you will be enrolled to Part 2a and assigned in a random manner (like a flip of a coin) to start taking (Z)-endoxifen and goserelin or start taking exemestane and goserelin treatment. For those with a diagnostic Ki-67 value of ≤10%, you will be enrolled in Part 2b and start taking (Z)-endoxifen alone. 

If, after 4 weeks of the assigned treatment, your biopsy shows the treatment is not working for you, your doctor may offer to modify your treatment. 

No, the focus of this study is premenopausal women. If you are not having periods and you are unsure if you are menopausal, your doctor will take a blood test to confirm.

Your trial doctor will make the decision if you are eligible for the study.  

It depends on which part you are participating in and how well you respond to treatment.  It could be as short as 3 months or as long as 9 months.

About 190

Your primary care physician or oncologist may be able to refer you to one of the clinical trial sites.