Efficacy and Safety of GTx-024 in Patients With Estrogen Receptor (ER)+/Androgen Receptor (AR)+ Breast Cancer
Condition: ER+ and AR+ Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: GTx-024
Intervention description: To determine whether either or both doses result in an acceptable clinical benefit rate.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 136.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine if GTx-024 at different dosages (9 mg or 18 mg) is
      effective and safe in the treatment of patients with metastatic or locally advanced Estrogen
      Receptor (ER)+ and Androgen Receptor (AR)+ breast cancer in postmenopausal women.
    

Eligibility criteria:

        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