Efficacy and Safety of GTx-024 in Patients With Androgen Receptor-Positive Triple Negative Breast Cancer (AR+ TNBC)
Condition: Triple Negative Breast Cancer
MeSH terms: Breast Neoplasms; Triple Negative Breast Neoplasms
Intervention: GTx-024
Intervention description: GTx-024 softgel capsules will be administered once-daily to a total dose of 18 mg
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine if GTx-024 is effective and safe in the treatment
      of patients with advanced, androgen receptor positive triple negative breast cancer (AR+
      TNBC).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Able and willing to give voluntary, written and signed, informed consent

          -  Women ≥ 18 years of age

          -  Women with TNBC who have received at least one but no more than two prior chemotherapy
             regimens for TNBC

          -  Confirmation of AR+ (defined as ≥ 10% nuclear AR staining by immunohistochemistry
             [IHC]) TNBC in either the primary or metastatic lesion, assessed during the screening
             period by a local laboratory or by medical history

          -  TNBC confirmed by medical history as: human epidermal growth factor receptor 2
             [HER2]-negative (confirmed by 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); estrogen receptor (ER) negative
             (confirmed as ER expression less than or equal to 1% positive tumor nuclei);
             progesterone receptor negative (confirmed as progesterone receptor expression less
             than or equal to 1% positive tumor nuclei)

          -  Availability of paraffin embedded or formalin fixed tumor tissue; OR, a minimum of 10
             and up to 20 slides of archived tumor tissue for central laboratory confirmation of AR
             status and molecular subtyping. Metastatic tumor tissue is preferred when possible

          -  Subjects must have either measurable disease or bone-only non-measurable disease,
             evaluable according to RECIST 1.1

          -  Subjects with bone metastases should be treated with intravenous bisphosphonates or
             subcutaneous denosumab (or investigator preferred standard of care) prior to and
             during the trial, unless there is a contraindication or subject intolerance to these
             therapies

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 at the time of
             screening and enrollment

          -  Negative pregnancy test in women of childbearing potential (premenopausal or less than
             12 months of amenorrhea post-menopause, and who have not undergone surgical
             sterilization), no more than 7 days before the first dose of study treatment

          -  For women of childbearing potential who are sexually active, agreement to use a highly
             effective, non-hormonal form of contraception during and for at least 6 months after
             completion of study treatment; OR, a fertile male partner willing and able to use
             effective non-hormonal of contraception (barrier method of contraception in
             conjunction with spermicidal jelly, or surgical sterilization) during and for at least
             6 months after completion of study treatment

          -  Adequate organ function as shown by:

               -  Absolute neutrophil count ≥ 1,000 cells/mm3

               -  Platelet count ≥ 100,000 cells/mm3

               -  Hemoglobin ≥ 9 g/dL

               -  Serum aspartate aminotransferase (AST) and alanine aminotransferase (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 time
                  (aPTT), or partial thromboplastin time (PTT) < 1.5 × ULN (unless on anticoagulant
                  treatment at screening)

          -  Able to swallow capsules

          -  Any toxicity from prior chemotherapy has resolved or Grade 1 (NCI-CTCAE, Version 4.0)

        Exclusion Criteria:

          -  Life expectancy < 4 months;

          -  Subjects with radiographic evidence of central nervous system (CNS) metastases as
             assessed by computerized tomography (CT) or magnetic resonance imaging (MRI) that are
             not well controlled (symptomatic or requiring control with continuous corticosteroid
             therapy [e.g., dexamethasone]). Note: Subjects with CNS metastases are permitted to
             participate in the study if the CNS metastases are medically well controlled prior to
             screening (as assessed by the Investigator) after receiving local therapy
             (irradiation, surgery, etc.)

          -  Radiotherapy within 14 days prior to first dose of study treatment

          -  Have, in the judgment of the Investigator, a clinically significant concurrent illness
             or psychological, familial, sociological, geographical, or other concomitant condition
             that would not permit adequate follow-up and compliance with the study protocol

          -  Positive hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection at screening

          -  Positive human immunodeficiency virus (HIV) infection at screening

          -  Prior treatment with any anti-androgens, including but not limited to, enzalutamide
             and bicalutamide

          -  Major surgery within 28 days of the first dose of study treatment

          -  Be currently taking or have previously taken testosterone, methyltestosterone,
             oxandrolone (Oxandrin®), oxymetholone, danazol, fluoxymesterone (Halotestin®),
             testosterone-like agents (such as dehydroepiandrosterone, androstenedione, and other
             androgenic compounds, including herbals), or anti-androgens

          -  Treatment with any of the following hormone replacement therapies, unless discontinued
             at least 14 days prior to the first dose of study treatment:

               -  Estrogens

               -  Megesterol acetate

          -  Treatment with any investigational agent within 28 days before the first dose of study
             treatment

          -  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

          -  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)

          -  Current treatment with intravenous bisphosphonate or denosumab with elevated serum
             calcium corrected for albumin or ionized calcium levels outside institutional normal
             limits at screening

          -  History of non-compliance to medical regimens

          -  Subjects unwilling to or unable to comply with the protocol procedures as assessed by
             the Investigator

          -  Concurrent participation in another therapeutic clinical trial