Estrogen Receptor Positive and Androgen Receptor Positive Breast Cancer MedDRA version: 19.0 Level: PT Classification code 10055113 Term: Breast cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 19.0 Level: LLT Classification code 10070575 Term: Estrogen receptor positive breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 19.0 Level:
Conditions
Sponsors
GTx, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Adult postmenopausal women with metastatic or recurrent locally advanced ER+/AR+ BC. Subject Inclusion criteria: Subjects eligible for inclusion in this study must meet all of the following criteria: 1. Adult women (= 18 years of age) with metastatic orrecurrent 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 2. 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) 3. 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) 4. 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 5. 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 6 months prior to screening) is permitted. 6. Radiological or clinical evidence (bone scan, computerized tomography [CT], and magnetic resonance Imaging [MRI]) of recurrence or progression within 30 days before randomization 7. Subject must have either measurable disease or bone-only non-measurable disease, evaluable according to RECIST 1.1 8. Adequate organ function as shown by: ?- Absolute neutrophil count (ANC) = 1,000 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) or activated partial thromboplastin (aPTT) < 1.5 × ULN (unless on anticoagulant treatment at screening) 9. Subject has an Eastern Cooperative Oncology Group (ECOG) performance status 4 0 or 1 10. Subjects with bone metastases should be tre
Exclusion criteria
Exclusion criteria: Subjects eligible for this study must not meet any of the following criteria: 1. Previously received > 1 course of chemotherapy (not including immunotherapies or targeted therapies) for the treatment of metastatic BC 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 2. Known hypersensitivity to any of the GTx-024 components or subjects previously received treatment with Selective Androgen Receptor Modulator (SARM) 3. 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.) 4. 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 5. Currently receiving hormone replacement therapy, unless discontinued prior to screening 6. Subjects positive for Human Immunodeficiency Virus (HIV) 7. 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. 8. Major surgery within 28 days before randomization 9. Positive hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection at screening 10. History of non-compliance to medical regimens 11. Subjects unwilling to or unable to comply with the protocol 12. Subject is currently receiving treatment with any agent listed on the prohibited medication list (See Section 6.6 Concomitant Medications/Treatments for complete list) 13. Treatment with any investigational product within < 4 half-lives for each individual investigational product OR within 28 days prior to randomization 14. Current treatme
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary efficacy objective of this trial is to estimate the CBR at 24 weeks (defined as CR, PR, or SD) (by RECIST 1.1) of GTx-024 9 mg and of GTx-024 18 mg given PO daily in subjects with ER+/AR+ BC who have centrally confirmed AR+ status. ;Secondary Objective: Secondary efficacy objectives: ? Estimate the CBR at 24 weeks (by RECIST 1.1) of GTx-024 9 mg and 18 mg in all subjects randomized who receive at least one dose of study medication (the FAS) regardless of AR status as determined by the central laboratory The following secondary efficacy objectives apply to both centrally confirmed AR+ subjects (the evaluable subset of theFAS) as well as to all subjects in the FAS: ? Estimate the objective response rate (ORR; defined as CR or PR) (by RECIST 1.1) of GTx-024 9 mg and 18 mg at 24 weeks ? Estimate the best overall response rate (BOR) of GTx-024 9 mg and 18 mg ? Estimate the progression free survival (PFS) of subjects receiving GTx-024 9 mg and 18 mg ? Estimate the time to progression (TTP) of subjects receiving GTx-024 9 mg and 18 mg ? Estimate duration of response (time from documentation of tumor response to disease progression or death) of subjects receiving GTx-024 9 mg and 18 mg Safety objective Pharmacokinetic objective;Primary end point(s): Primary efficacy endpoint Tumor response in terms of clinical benefit will be assessed by RECIST 1.1 criteria from centrally read CT scans obtained at the 24 week assessment. Tumor response isjudged relative to baseline tumor assessments. An evaluable subject will be considered to have a response of CB if the assessment indicates CR, PR, or SD. The primary assessment is among evaluable subjects in the FAS at 24 weeks in each of the 9 mg and 18 mg arms. An evaluable subject who does not have a week 24 assessment for any reason remains in the evaluable subset of the FAS and is considered a failure to achieve CB (CR, PR, or SD).;Timepoint(s) of evaluation of this end point: week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints ?- CBR in the FAS and PPS at 24 weeks in each of the 9 mg and 18 mg arms. The following secondary efficacy endpoints will be assessed among subjects in each of the 9 mg and 18 mg arms among the evaluable subjects, the FAS, and the PPS: ?- ORR (CR or PR assessed by RECIST 1.1 criteria) at 24 weeks - Best (confirmed) overall response rate (BOR). BOR is defined as the best observed response for each subject up to and including the EOT. Reponses of CR or PR should be confirmed by a repeat assessment at least 4 weeks later. ?- PFS: PFS is defined as the time from randomization until objective tumor progression or death due to any cause. Subjects who have no PFS events will be censored at the date of the last adequate tumor assessment. If the subject has no post-baseline tumor assessments, they will be censored at the time of randomization ?- TTP: TTP is defined as the time from randomization until objective tumor progression or death due to disease progression. Subjects who have not progressed will be censored at the date of the last adequate tumor assessment. If the subject has no post-baseline tumor assessments but is known to be alive, they will be censored at the time of randomization ?- Duration of response: Duration of response, in responders, is defined as the period from the date of initial CR or PR until the date of disease progression or death from any cause. Only subjects with BOR of CR or PR (i.e., responders) will be included in the analysis of duration of response. Subjects with no documented progression or death after CR or PR will be censored at the last date at which they are known to have had the CR or PR Safety endpoints The following safety endpoints will be assessed among evaluable subjects as well as all subjects enrolled and treated: ?- AEs and concomitant medications ?- Laboratory examinations (clinical chemistry, hematology, and urinalysis) ? -Physical examinations ?- Vit | — |
Countries
Australia, Bulgaria, Czech Republic, Hungary, Lithuania, Romania, Ukraine, United Kingdom, United States
Contacts
Public ContactMayzie Johnston , Vice President
GTx, Inc.
Outcome results
None listed