Orteronel as Monotherapy in Patients With Metastatic Breast Cancer (MBC) That Expresses the Androgen Receptor (AR)

Inclusion Criteria

• •1. Voluntary written informed consent before performance of any study-related procedure not part of normal medical care
• •2. Patients must have MBC that is measurable or evaluable as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. Patients with metastases limited to the bones are eligible.
• •3. Patients with breast tumors that are AR+ (≥10% staining by immunohisto-chemistry). Archived tumor tissue from a primary biopsy or metastatic lesion for centralized determination of AR expression is mandatory. If tissue is limited, the additional correlative testing is optional. If tissue is not available, a patient will not be eligible for enrollment into the study. Patients may enroll based on local laboratory AR assessment, but will need to submit tissue for confirmation at the central laboratory.
• •4. In addition to having AR+ tumors, patients must fit into 1 of the 2 following categories:
• •* Triple negative (ER-/PR-/HER2-) (Note: This group of patients must have received at least 1 and up to 3 prior chemotherapy regimens in the advanced setting.)
• •* ER+ and/or PR+ (Note: This group of patients must have received at least 1 and up to 3 prior hormonal therapies and at least one prior chemotherapy treatment in the advanced setting. HER2+ patients in this group must have received a minimum of 2 lines of HER2-directed therapy in the advanced setting.) This group of patients may be pre-menopausal with ovarian suppression or post-menopausal. LHRH agonists maybe used to render ovarian suppression with post-menopausal ranges of estradiol or FSH per institutional guidelines.
• •5. Female or male patients ≥18 years-of-age
• •6. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
• •7. Patient has recovered (to Grade ≤1) from all clinically significant toxicities related to prior antineoplastic therapies (with the exception of alopecia)
• •8. Adequate hematological function, defined as:
• •* Absolute neutrophil count (ANC) ≥1.25 x 109/L
• •* Platelets ≥75 x 109/L
• •* Hemoglobin ≥9 g/dL
• •9. Adequate liver function, defined as:
• •* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x the upper limit of normal (ULN), if no liver involvement or ≤5 x ULN with liver involvement
• •* Total bilirubin ≤1.5 times the upper limit of normal (ULN) (in patients with known Gilbert Syndrome, a total bilirubin ≤3.0 x ULN, with direct bilirubin ≤1.5 x ULN)
• •10. Adequate renal function, defined as:
• •* Creatinine ≤1.5 x ULN or creatinine clearance ≥40 mL/min as calculated by the Cockcroft-Gault method
• •11. Screening calculated LVEF of ≥50% by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan
• •12. Ability to swallow and retain oral medication
• •13. Male patients (even those post vasectomy) who are willing to use adequate contraceptive measures or abstain from heterosexual intercourse during the entire study treatment period and for 4 months after the last dose of study drug
• •14. Female patients who are not of child-bearing potential and female patients of child-bearing potential who agree to use adequate contraceptive measures or abstain from heterosexual intercourse during the entire study treatment period and for 4 months after the last dose of study drug, who are not breastfeeding, and who have had a negative serum/urine pregnancy test ≤7 days prior to dosing
• •15. Life expectancy of ≥3 months
• •16. Willingness and ability to understand the nature of this study and to comply with the study and follow-up procedures.
• •17. Diagnosis or treatment for another malignancy within 2 years of enrollment, with the exception of adequately treated in-situ carcinoma of the cervix, uteri, basal or squamous cell carcinoma or non-melanomatous skin cancer
• •18. Inability or unwillingness (including psychological, familial, sociological, or geographical conditions) to comply with study and/or follow-up procedures as outlined in the protocol.
• •19. Use of a prohibited concomitant medication that cannot be safely discontinued or substituted.