(Z)-Endoxifen for the Treatment of Premenopausal Women With ER+/HER2- Breast Cancer
(Z)-Endoxifen for the Treatment of Premenopausal Women With ER+/HER2- Breast Cancer
This open-label research study is studying (Z)-endoxifen as a possible treatment for
pre-menopausal (still having periods) women with ER+/HER2- breast cancer. (Z)-endoxifen is a
selective estrogen receptor modulator or "SERM." SERMs work to treat cancer by blocking the
body's natural estrogen from binding to cancer cells. This study includes a pharmacokinetic
part (PK, how the drug works in your body) and a treatment part. The primary purpose of the
study is to see how (Z)-endoxifen works on tumor cell growth by monitoring a cancer marker
called Ki-67. Ki-67 will be measured by biopsy of the breast after about 4 weeks of
treatment. If your cancer is responding to treatment based on the Ki-67 results, you may
continue treatment up to 24 weeks or until surgery.
The PK part of the study will be enrolled first, enrolling about 18 study participants who
will all receive oral once daily (Z)-endoxifen treatment. 12 of these participants will be
randomly assigned to treatment with an equal (50/50) chance to be assigned to (Z)-endoxifen
or (Z)-endoxifen + goserelin (a medication given to block the ovaries from making estrogen
and is also called ovarian suppression). This part of the study will help select the dose of
(Z)-endoxifen to use in the treatment part by measuring the levels of (Z)-endoxifen in the
blood stream and determine how long it takes for the body to remove it.
About 160 study participants will be enrolled in the treatment part. The treatment part will
help to determine how oral once daily (Z)-endoxifen, when taken by itself, compares to oral
once daily exemestane (a medication that decreases the amount of estrogen in the body, also
known as an aromatase inhibitor) and monthly injections of goserelin. Exemestane and
goserelin taken together is a standard treatment regimen for premenopausal patients with
ER+/HER2- breast cancer. Study participants are randomly assigned to treatment with an equal
(50/50) chance to be assigned to (Z)-endoxifen or standard treatment.
Study participation is up to 24 weeks of treatment followed by surgery.
pre-menopausal (still having periods) women with ER+/HER2- breast cancer. (Z)-endoxifen is a
selective estrogen receptor modulator or "SERM." SERMs work to treat cancer by blocking the
body's natural estrogen from binding to cancer cells. This study includes a pharmacokinetic
part (PK, how the drug works in your body) and a treatment part. The primary purpose of the
study is to see how (Z)-endoxifen works on tumor cell growth by monitoring a cancer marker
called Ki-67. Ki-67 will be measured by biopsy of the breast after about 4 weeks of
treatment. If your cancer is responding to treatment based on the Ki-67 results, you may
continue treatment up to 24 weeks or until surgery.
The PK part of the study will be enrolled first, enrolling about 18 study participants who
will all receive oral once daily (Z)-endoxifen treatment. 12 of these participants will be
randomly assigned to treatment with an equal (50/50) chance to be assigned to (Z)-endoxifen
or (Z)-endoxifen + goserelin (a medication given to block the ovaries from making estrogen
and is also called ovarian suppression). This part of the study will help select the dose of
(Z)-endoxifen to use in the treatment part by measuring the levels of (Z)-endoxifen in the
blood stream and determine how long it takes for the body to remove it.
About 160 study participants will be enrolled in the treatment part. The treatment part will
help to determine how oral once daily (Z)-endoxifen, when taken by itself, compares to oral
once daily exemestane (a medication that decreases the amount of estrogen in the body, also
known as an aromatase inhibitor) and monthly injections of goserelin. Exemestane and
goserelin taken together is a standard treatment regimen for premenopausal patients with
ER+/HER2- breast cancer. Study participants are randomly assigned to treatment with an equal
(50/50) chance to be assigned to (Z)-endoxifen or standard treatment.
Study participation is up to 24 weeks of treatment followed by surgery.
Breast
Phase II
Adults
Hormonal Therapy
(Z)-Endoxifen,
Exemestane,
Goserelin acetate (Zoledex)
Abramson, Vandana
International
Vanderbilt University
01-21-2025
Eligibility
18 Years
FEMALE
NO
Inclusion Criteria:
Premenopausal women 18 years or older
Not lactating, pregnant, or planning to become pregnant in the next year
Agree to use at least one non-hormonal highly effective method of contraception for the entire duration of study participation.
ER+/HER2-: [ER] 67% or Allred Score 6-8) / HER2- (histologically confirmed) using American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines
Clinical T2 or T3 and N0 or N1 invasive breast cancer (per American Joint Committee on Cancer [AJCC] 8th edition clinical staging)
Nottingham Grade 1 or 2
ECOG Performance Status (ECOG PS) of 0 to 2
Exclusion Criteria:
Inflammatory breast cancer; bilateral disease (DCIS/LCIS in contralateral breast OK)
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
Uncontrolled intercurrent illness including, but not limited to:
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 (defined as blood pressure > 160/90 mm Hg)
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
Known cataracts or retinopathy
History of deep vein thrombosis (DVT)/pulmonary embolism (PE)
Known activated protein C (APC) resistance, an inherited coagulation disorder
Creatine clearance 60 ml/min
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 during the study or within 1 week of registration; androgen therapy
Allergy to endoxifen, goserelin, or exemestane or any of their components
Participation in another investigational clinical trial 6 months of registration
Known metastatic disease
Premenopausal women 18 years or older
Not lactating, pregnant, or planning to become pregnant in the next year
Agree to use at least one non-hormonal highly effective method of contraception for the entire duration of study participation.
ER+/HER2-: [ER] 67% or Allred Score 6-8) / HER2- (histologically confirmed) using American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines
Clinical T2 or T3 and N0 or N1 invasive breast cancer (per American Joint Committee on Cancer [AJCC] 8th edition clinical staging)
Nottingham Grade 1 or 2
ECOG Performance Status (ECOG PS) of 0 to 2
Exclusion Criteria:
Inflammatory breast cancer; bilateral disease (DCIS/LCIS in contralateral breast OK)
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
Uncontrolled intercurrent illness including, but not limited to:
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 (defined as blood pressure > 160/90 mm Hg)
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
Known cataracts or retinopathy
History of deep vein thrombosis (DVT)/pulmonary embolism (PE)
Known activated protein C (APC) resistance, an inherited coagulation disorder
Creatine clearance 60 ml/min
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 during the study or within 1 week of registration; androgen therapy
Allergy to endoxifen, goserelin, or exemestane or any of their components
Participation in another investigational clinical trial 6 months of registration
Known metastatic disease
