Study of Panobinostat Monotherapy in Women With HER2-negative Locally Recurrent or Metastatic Breast Cancer

Inclusion Criteria

• Written informed consent obtained prior to any study-related procedures
• Women ≥ 18 years old
• Patients with an ECOG performance status of ≤ 2 assessed within 2 weeks (14 days) prior to registration
• Histologically or cytologically confirmed breast cancer with locally recurrent or radiological evidence of metastatic disease. Locally recurrent disease must not be amenable to resection with curative intent.
• Measurable disease per RECIST (Response Evaluation Criteria in Solid Tumor) guidelines
• HER2-negative patients by local laboratory testing (IHC 0 or 1+ staining, IHC 2+ staining but in situ hybridization negative, or in situ hybridization negative).
• ER and PgR testing from a local laboratory is required prior to patient registration
• For Arm I: at least two lines of prior endocrine therapy (in adjuvant and/or metastatic settings) are required. Up to two prior cytotoxic chemotherapies are allowed in the metastatic setting (prior adjuvant and neoadjuvant chemotherapy is allowed).
• For Arm II: up to 2 prior cytotoxic chemotherapy regimens for treatment of metastatic or locally recurrent breast cancer are allowed.
• Complete radiological tumor measurement within 4 weeks (28 days) prior to registration:
• Chest: CT scan with intravenous contrast if the contrast is not medically contraindicated or MRI
• Abdomen: CT scan with intravenous or oral contrast if the contrast is not medically contraindicated or MRI
• Brain: CT scan or MRI
• Bone: Whole body Bone Scintigraphy
• Patients must meet the following laboratory criteria within 2 weeks (14 days) prior to registration:
• Hematology
• Neutrophil count of > 1200/mm3
• Platelet count of > 100,000/mm3
• Hemoglobin ≥ 90 g/L
• Biochemistry
• AST/SGOT and ALT/SGPT ≤ 2.5 x upper limit of normal (ULN) or ≤ 5.0 x ULN if the transaminase elevation is due to disease involvement
• Serum bilirubin ≤ 1.5 x ULN
• Serum creatinine ≤ 1.5 x ULN or 24-hour creatinine clearance ≥ 50 mL/min
• Serum potassium, sodium, magnesium, phosphorus, and calcium within normal limits for the institution
• Serum albumin ≥ LLN or 30g/L
• Clinically euthyroid function (TSH and free T4). (Patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism).
• LVEF assessment (2-D echocardiogram or MUGA scan) performed within 6 weeks prior to registration, showing a LVEF value > 50%
• Electrocardiogram performed within 1 week prior to registration (details about findings on the Electrocardiogram that are not acceptable for participating in the study are reported in the Exclusion criteria section)
• Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days prior to registration and agree to appropriate method of pregnancy prevention.
• Patient should have an archival tumor sample available for confirmation of HER2, Estrogen and Progesterone status by the central lab.

Exclusion Criteria

• Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer
• Patients who need valproic acid for any other medical condition during the study or within 5 days prior to first panobinostat treatment
• Patients who have received prior systemic anti-cancer therapy (cytotoxic chemotherapy, endocrine therapy, targeted therapy, monoclonal antibody or biologic therapy) or investigational agent within the last 4 weeks prior to registration (6 weeks for nitrosoureas and mitomycin; 2 weeks for capecitabine)
• Patients who have received prior radiotherapy to ≥ 25% of the bone marrow within the last 4 weeks prior to registration; local radiotherapy is allowed however all recently irradiated lesions should not be included in the measurable disease assessment.
• Patients who have received prior investigational agents within the last 4 weeks prior to registration
• Patients with unresolved diarrhea ≥CTCAE grade 1
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral panobin