Inclusion Criteria:
- Adult women (≥ 18 years of age) with metastatic or recurrent locally advanced BC, not
amenable to curative treatment by surgery or radiotherapy, with objective evidence of
disease progression.
- Women must have received ≥ 1 prior hormonal treatment(s) in the metastatic or
adjuvant setting. If the most recent hormonal treatment was in the metastatic
setting, duration of response (tumor regression or stabilization of disease) to
this specific course of therapy must be ≥ 6 months. If the most recent hormonal
treatment was in the adjuvant setting, duration of response (disease free) to
this specific course of therapy must be ≥ 3 years
- Histological or cytological confirmation of ER+ BC as assessed by a local laboratory
using slides, paraffin blocks, or paraffin sample or by medical history: ER+
(confirmed as ER expression more than or equal to 1% positive tumor nuclei)
- Human epidermal growth factor receptor 2 (HER2)-negative tumor by local laboratory
testing (immunohistochemistry [IHC] 0, 1+ regardless of fluorescence in situ
hybridization [FISH] ratio; IHC 2+ with FISH ratio lower than 2.0 or HER2 gene copy
less than 6.0; FISH ratio of 0, indicating gene deletion, when positive and negative
in situ hybridization [ISH] controls are present)
- Availability of paraffin embedded or formalin fixed tumor tissue; OR, a minimum of 10
and up to 20 slides of archived tumor tissue or new biopsy, if archived tissue is
unavailable for central laboratory confirmation of AR status and molecular subtyping.
Metastatic tumor tissue is preferred when possible.
- Postmenopausal women. Postmenopausal status is defined by the National Comprehensive
Cancer Network as either:
- Age ≥ 55 years and one year or more of amenorrhea
- Age < 55 years and one year or more of amenorrhea, with an estradiol assay < 20
pg/mL
- Age < 55 years and surgical menopause with bilateral oophorectomy a. Note:
Ovarian radiation or treatment with a luteinizing hormone-releasing hormone
(LH-RH) agonist (goserelin acetate or leuprolide acetate) is not permitted for
induction of ovarian suppression at the time of screening. Long term use (>6
months prior to screening) is permitted
- Radiological or clinical evidence (bone scan, computerized tomography [CT], and
magnetic resonance Imaging [MRI]) of recurrence or progression within 30 days before
randomization
- Subject must have either measurable disease or bone only non measurable disease,
according to RECIST1.1
- Adequate organ function as shown by:
- Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3
- Platelet count ≥ 100,000 cells/mm3
- Hemoglobin (Hgb) ≥ 9.0 g/dL
- Serum aspartate aminotransferase (AST) and alanine transaminase (ALT) ≤ 2.5 upper
limit of the normal range (ULN) (or ≤ 5 if hepatic metastases are present)
- Total serum bilirubin ≤ 2.0 × ULN (unless the subject has documented Gilbert
Syndrome)
- Alkaline phosphatase levels ≤ 2.5 × ULN (≤ 5 × ULN in subjects with liver
metastasis)
- Serum creatinine ≤ 2.0 mg/dL or 177 µmol/L
- International normalized ratio (INR), activated partial thromboplastin (aPTT), or
partial thromboplastin time (PTT) < 1.5 × ULN (unless on anticoagulant treatment
at screening)
- Subject has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Subjects with bone metastases should be treated with intravenous bisphosphonates or
subcutaneous denosumab (or investigator preferred standard of care) prior to and/or
during the trial, unless there is a contraindication or subject intolerance to these
therapies. For patients who are normocalcemic, therapy can be initiated at the time
the patient initiates study drug
- Subject is able to swallow capsules
- Able and willing to give voluntary, written and signed informed consent before any
screening procedure and according to local guidelines
Exclusion Criteria:
- Previously received > 1 course of chemotherapy (not including immunotherapies or
targeted therapies) for the treatment of metastatic
a. Note: Subjects may have received 1 course of chemotherapy prior to surgery for the
treatment of locally advanced disease and 1 course of chemotherapy for the treatment
of metastatic BC; however, if surgery could not be performed, this will count as the 1
chemotherapy course allowed prior to study
- Known hypersensitivity to any of the GTx-024 components or subjects previously
received treatment with SARM
- Subjects with radiographic evidence of central nervous system (CNS) metastases as
assessed by CT or MRI that are not well controlled (symptomatic or requiring control
with continuous corticosteroid therapy [e.g., dexamethasone])
a. Note: Subjects with CNS metastases are permitted to participate in the study if the
CNS metastases are medically well-controlled and stable for at least 28 days after
receiving local therapy (irradiation, surgery, etc.)
- Radiotherapy within 14 days prior to randomization except in case of localized
radiotherapy for analgesic purpose or for lytic lesions at risk of fracture, which can
then be completed within 7 days prior to randomization. Subjects must have recovered
from radiotherapy toxicities prior to randomization
- Currently receiving hormone replacement therapy, unless discontinued prior to
screening
- Subjects positive for Human Immunodeficiency Virus (HIV)
- Subject has a concomitant medical condition that precludes adequate study treatment
compliance or assessment, or increases subject risk, in the opinion of the
Investigator, such as but not limited to:
- Myocardial infarction or arterial thromboembolic events within 6 months prior to
Baseline or severe or unstable angina, New York Heart Association (NYHA) Class
III or IV disease, or a QTcB (corrected according to Bazett's formula) interval >
470 msec
- Serious uncontrolled cardiac arrhythmia grade II or higher according to NYHA
- Uncontrolled hypertension (systolic > 150 and/or diastolic > 100 mm Hg)
- Acute and chronic, active infectious disorders and non malignant medical
illnesses that are uncontrolled or whose control may be jeopardized by the
complications of this study therapy
- Impairment of gastrointestinal function or gastrointestinal disease that may
significantly alter the absorption of study drugs (e.g., ulcerative disease,
uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome)
- Another active cancer (excluding adequately treated basal cell carcinoma or
cervical intraepithelial neoplasia [CIN]/cervical carcinoma in situ or melanoma
in situ). Prior history of other cancer is allowed as long as there is no active
disease within the prior 5 years
- Major surgery within 28 days before randomization
- Positive hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection at screening
- History of non-compliance to medical regimens
- Subjects unwilling to or unable to comply with the protocol
- Subject is currently receiving treatment with any agent listed on the prohibited
medication list
- Treatment with any investigational product within < 4 half-lives for each individual
investigational product OR 28 days prior to randomization
- Current treatment with intravenous bisphosphonate or denosumab with elevated serum
calcium corrected for albumin or ionized calcium levels outside institutional normal
limits at screening
