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
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)
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
Parallel
(Z)-endoxifen
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
Druggoserelin 3.6 mg subcutaneous implant
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)
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.
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.
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)
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)
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)
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)
Click on the lead sponsor to view all of their trials.
Atossa Therapeutics, Inc.
Lead sponsor
InClin
Collaborator
