PIKNIC: This phase II trial is investigating the oral drug BYL719 as a monotherapy for people with advanced metastatic breast cancer after first line treatmentA Phase II Exploratory, Open-label, Single Arm Study of BYL719 Monotherapy, a Selective Phosphatidylinositol 3-kinase (PI3K) Alpha Inhibitor, in Adult Patients With Advanced Breast Cancer Progressing After First Line Therapy.

Exclusion

Patients eligible for this study must not meet any of the following criteria:

• Patient has a primary central nervous system (CNS) tumor or CNS tumor involvement.
• However patients with metastatic CNS tumors may participate in this study if the patient is:
• Four weeks from prior therapy completion (including radiation and surgery) to starting study treatment
• Clinically stable with respect to the CNS tumor at the time of screening
• Not receiving steroid therapy
• Patient with diabetes mellitus (fasting glucose >120mg/dl or 6.7 mmol/L), or documented steroid-induced diabetes mellitus
• Patient has a history of another malignancy within 2 years prior to starting study treatment, except for cured basal cell carcinoma of the skin or excised carcinoma in situ of the cervix.
• Patient who has not recovered to grade 1 or better (except alopecia) from related side effects of any prior antineoplastic therapy
• Patient who has had systemic chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to study entry.
• Patient who has received radiotherapy ≤ 4 weeks prior to starting study drugs, with exception of palliative radiotherapy (≤ 2 weeks prior to starting study drugs), who has not recovered from side effects of such therapy to baseline or Grade ≤ 1 and/or from whom ≥ 30% of the bone marrow was irradiated. Target lesions should not have had previous irradiation unless have progressed post treatment.
• Patient who has undergone major surgery ≤ 4 weeks prior to starting study treatment or who has not recovered from side effects of such procedure.
• Patient has a clinically significant cardiac disease or impaired cardiac function, such as:
• Congestive heart failure (CHF) requiring treatment (New York Heart Association (NYHA) Grade ≥ 2), left ventricular ejection fraction (LVEF) < 50% as determined by multi-gated acquisition (MUGA) scan or echocardiogram (ECHO)
• History or current evidence of clinically significant cardiac arrhythmias, atrial fibrillation and/or conduction abnormality, e.g. congenital long QT syndrome, high-grade/complete AV-blockage
• Acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass graft (CABG), coronary angioplasty, or stenting), < 3 months prior to screening
• QT interval adjusted according to Fredericia (QTcF) > 480 msec on screening ECG.
• Patient who has any severe and/or uncontrolled medical conditions such as:
• Active or uncontrolled severe infection,
• Liver disease such as cirrhosis, decompensated liver disease, and chronic hepatitis (i.e. quantifiable hepatitis B HBV-DNA and/or positive HbsAg, quantifiable hepatitis C HCV-RNA)
• Known severely impaired lung function (spirometry and DLCO 50% or less of normal and O2 saturation 88% or less at rest on room air)
• Active, bleeding diathesis;
• Uncontrolled arterial hypertension defined by blood pressure > 140/100 mm Hg at rest (average of 3 consecutive readings 5 min apart)
• Chronic treatment with corticosteroids or other immunosuppressive agent
• Patient who is currently receiving medication with a known risk of prolonging the QT interval or inducing Torsades de Pointes (TdP) and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug treatment.
• Patient who has participated in a prior investigational study within 30 days prior to enrollment.
• Patient who is currently receiving treatment with drugs known to be moderate or strong inhibitors or inducers of cytochrome isoenzymes CYP34A or CYP2C8. The patient must have discontinued moderate and strong inducers of both enzymes for at least one week and must have discontinued strong and moderate inhibitors before the start of treatment. Switching to a different medication prior to start of treatment is allowed; Refer to Appendix 1
• Patient with impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral BYL719 (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
• Patient with known positive serology for human immunodeficiency virus (HIV).
• Patients who have received live attenuated vaccines within 1 week of start of study drug and during the study. Patient should also avoid close contact with others who have received live attenuated vaccines. Examples of live attenuated vaccines include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella and TY21a typhoid vaccines.
• Pregnant or nursing (lactating) woman, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test (> 5 mIU/mL).
• Patient who does not apply highly effective contraception during the study and through the duration as defined below after the final dose of study treatment.