Androgen Receptor-Positive Triple Negative Breast Cancer (AR+ TNBC) MedDRA version: 19.0 Level: PT Classification code 10057654 Term: Breast cancer female System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 19.0 Level: LLT Classification code 10072737 Term: Advanced breast cancer
Conditions
Interventions
Product Name: enobosarm
Product Code: GTx-024
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: enobosarm
Current Sponsor code: GT
Sponsors
GTx, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Adult women with advanced TNBC with centrally confirmed AR+. Subject Inclusion Criteria: Subjects eligible for inclusion in this study must meet all of the following criteria: 1. Able and willing to give voluntary, written and signed, informed consent; 2. Women = 18 years of age; 3. Women with TNBC who have received at least one but no more than two prior chemotherapy regimens for the treatment of advanced or metastatic TNBC; 4. Confirmation of AR+ (defined as = 10% nuclear AR staining by immunohistochemistry [IHC]) TNBC in either the primary or metastatic lesion, assessed prior to the start of or during the screening period by a local laboratory or by medical history; 5. 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); 6. 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; 7. Subjects must have either measurable disease or bone only nonmeasurable disease according to RECIST 1.1; 8. 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 subjects who are normocalcemic, therapy can be initiated at the time the subject initiates study drug; 9. Eastern Cooperative Oncology Group (ECOG) performance status 3 0 or 1 at the time of screening and enrollment; 10. Negative serum 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; 11. 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 means 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; 12. Adequate organ function as shown by: ? Absolute neutrophil count = 1,500 cells/mm3 ? Platelet count = 100,000 cells/mm3 ? Hemoglobin = 9 g/dL ? Serum aspartate aminotransferase (AST) and alani
Exclusion criteria
Exclusion criteria: Subjects eligible for this study must not meet any of the following criteria: 1.Life expectancy 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); 14. Current treatment with intra
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary efficacy objective of this trial is to estimate the CBR at 16 weeks (defined as CR, PR, or SD) (by RECIST 1.1) of GTx-024 18 mg given PO daily in subjects with TNBC and centrally confirmed AR+ status. Safety objective: To describe the safety profile of GTx-024 18 mg PO daily in subjects with TNBC and centrally confirmed AR+ as well as in all subjects enrolled and treated. Pharmacokinetic objective: To describe the plasma concentrations of GTx-024 and GTx 024 glucuronide at each of the assessed time points. ; Secondary Objective: • Estimate the CBR at 16 weeks (by RECIST 1.1) of GTx 024 18 mg in all subjects enrolled who receive at least one dose of study medication 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 the FAS) 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 18 mg at 16 weeks • Estimate the CBR (by RECIST 1.1) of GTx-024 18 mg at 24 weeks • Estimate the ORR (CR or PR) (by RECIST 1.1) of GTx-024 18 mg at 24 weeks • Estimate the best overall response rate of GTx 024 18 mg • Estimate the progression free survival of subjects receiving GTx-024 18 mg • Estimate the time-to-progression of subjects receiving GTx-024 18 mg • Estimate duration of response (from documentation of response to disease progression or death) of subjects receiving GTx-024 18 mg • Estimate overall survival (OS) ; 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 1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • CBR in the FAS at 16 weeks. The following secondary efficacy endpoints will be assessed among evaluable subjects (if not already listed above), the FAS (if not already listed above), and the PPS: • CBR at weeks 16 and 24 • ORR (PR or CR assessed by RECIST 1.1 criteria) at weeks 16 and 24. • 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 PR or CR should be confirmed by a repeat assessment at least 4 weeks later. • PFS: PFS is defined as the time from treatment initiation until objective tumor progression or death. 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 enrollment. • TTP: TTP is defined as the time from treatment initiation until objective tumor progression or death due to PD. 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 was known to be alive, they will be censored at the time of enrollment. • Duration of response: Duration of response, in responders, is defined as the period from the date of initial PR or CR until the date of PD 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 | — |
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