Clinical trials are carefully designed research studies to study 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 women 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). These medications may cause unpleasant side effects and are inconvenient to take.  Over 40% of premenopausal women stop taking these ovarian function suppression medications earlier than their doctor prescribed. 

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 - 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.   

About 6-18 people will participate in Part 1. Six people have completed Part 1.  An additional 12 people will participate in this part and will randomly receive (50/50 chance like a flip of a coin) either (Z)-endoxifen once daily by mouth for 4 weeks or (Z)-endoxifen once daily by mouth for 4 weeks + one injection of goserelin about every 28 days (this is OFS).  You and your doctor will know which treatment you will receive (open-label).  You will be closely monitored for safety (with blood draws, tests, and interviews) and disease progression (by MRIs).  This part will also include several blood draws at several visits to measure the amount of (Z)-endoxifen in your blood.  A breast biopsy will be taken from the 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 sensitive, your doctor may offer to continue treatment for up to 24 weeks.  Once treatment is complete, you will go on to have surgery.  If you respond to treatment, your surgery may be less invasive.

2) Part 2 - See if (Z)-endoxifen by itself is just as effective at decreasing cancer cell growth compared to a standard treatment.  

About 160 people will participate in Part 2. Participants will be randomized (50/50 like a flip of a coin) to receive (Z)-endoxifen once daily by mouth or 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).  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. If after 4 weeks of treatment, your biopsy shows the treatment is not working for you, your doctor may offer to modify your treatment.  You would then have an additional breast biopsy after about 8-12 weeks of treatment to see if your modified treatment is working for you. 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. 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).  

You will be assigned in a random manner (like a flip of a coin) to start taking (Z)-endoxifen or start taking exemestane and goserelintreatment. 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. You must be having periods. 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.

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