Copanlisib (BAY 80-6946) in Combination With Gemcitabine and Cisplatin in Advanced Cholangiocarcinoma

Exclusion Criteria

• •Must not have received any systemic chemotherapy for advanced biliary cancer.
• •Eastern Cooperative Oncology Group (ECOG) Performance Status Assessment of 0 or 1.
• •Must have radiographic measurable disease.
• •Life expectancy of at least 12 weeks (3 months).
• •For patients who have received prior radiation, cryotherapy, radiofrequency ablation, therasphere, ethanol injection, transarterial chemoembolization (TACE) or photodynamic therapy, the following criteria must be met: 28 days have elapsed since that therapy; Lesions that have not been treated with local therapy must be present and measureable.
• •Adequate bone marrow, liver and liver function.
• •Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of study drug. Men and women of childbearing potential must agree to use adequate contraception beginning at the signing of the Informed Consent Form (ICF) until at least 3 months after the last dose of study drug.
• •Must be able to swallow and retain oral medication.
• •Availability of archival tumor tissue for biomarkers analysis (minimum of 10 unstained slides are optional). Specimen from primary site will be allowed.
• •Previous or concurrent cancer within 3 years prior to treatment start except for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors \[Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)\].
• •Congestive heart failure \> New York Heart Association (NYHA) class 2.
• •Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months).
• •Myocardial infarction less than 6 months before study enrollment
• •Uncontrolled hypertension (blood pressure ≥ 150/90 mmHg despite optimal medical management).
• •Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months before enrollment.
• •Non-healing wound, ulcer, or bone fracture.
• •Active clinically serious infections (\> Common Terminology Criteria for Adverse Events (CTCAE) grade 2).
• •Known history of human immunodeficiency virus (HIV) infection.
• •Known active Hepatitis B or C.
• •A seizure disorder requiring medication.
• •Evidence or history of bleeding diathesis. Any hemorrhage or bleeding event ≥ CTCAE Grade 3 within 4 weeks of start of study enrollment.
• •Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.
• •Known hypersensitivity to any of the test drugs, test drug classes, or excipients in the formulation.
• •History or concurrent condition of interstitial lung disease of any grade or severely impaired pulmonary function.
• •Unresolved toxicity higher than CTCAE grade 1 attributed to any prior therapy/procedure excluding alopecia.
• •HbA1c \>8.5% or fasting plasma glucose \> 160 mg/dL at screening.
• •Concurrent diagnosis of pheochromocytoma.
• •Women who are pregnant or breast feeding.
• •Any illness or medical conditions that are unstable or could jeopardize the safety of the patient and his/her compliance in the study.