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. 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.
• 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
‣ 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.