The PI3K (phosphoinositol 3-Kinase) inhibitor Copanlisib and the MEK (mitogen-activated protein kinase) inhibitor Refametinib (BAY86-9766)have both been tested as single agent treatments in other phase I studies. This study will test the combination of these two drugs to try and answer the following questions:

1. What are the side effects of the combination of Copanlisib and Refametinib (BAY86-9766)when given together at different/increasing dose levels?
2. What dose level of Copanlisib and Refametinib (BAY86-9766) should be tested in future clinical research studies?
3. How much Copanlisib is in the blood at specific times after administration and does adding Refametinib (BAY86-9766) have an affect?
4. How much Refametinib (BAY86-9766) is in the blood at specific times after administration and does adding Copanlisib have an affect?
5. Does the combination of Refametinib (BAY86-9766) and Copanlisib have an effect on tumors?

Inclusion Criteria:

• Age greater than/equal to 18 years old

• ECOG Performance Status of 0 - 1

• Life expectancy of at least 12 weeks

• Patients with advanced, histologically or cytologically confirmed solid tumors, refractory to any standard therapy or have no standard therapy available

• LVEF (left ventricular ejection fraction) > or = to the lower limit of normal for the institution

• Radiographically or clinically evaluable tumor

• Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 14 days prior to start of first dose:

  • Hemoglobin > 9.0 g/dL
  • Absolute neutrophil count (ANC) > or = 1500/mm3
  • Platelet count > or = 100,000 /mm3
  • Total bilirubin < or = 1.5 times the upper limit of normal
  • ALT (alanine aminotransferase) and AST (aspartate aminotransferase) < or = 2.5 x upper limit of normal (< or = 5 x upper limit of normal for patients with liver involvement)
  • PT-INR (prothrombin-international normalized ratio) and PTT (partial thromboplastin time) < or = 1.5 times the upper limit of normal
  • Serum creatinine < or = 1.5 times the upper limit of normal

Exclusion Criteria:

• History of impaired cardiac function or clinically significant cardiac disease (i.e. congestive heart failure (CHF) NYHA (New York Heart Association) Class III or IV); active coronary artery disease, myocardial infarction within 6 months of study entry; new onset or unstable angina within 3 months of study entry, or cardiac arrhythmias requiring anti-arrhythmic therapy
• Type 1 or type 2 diabetes mellitus or fasting glucose > 125 mg/dL or HgBA1c > or = 7.0
• Use of systemic corticosteroids within 2 weeks of study entry
• History of retinal vein occlusion
• Known glucose-6-phosphate dehydrogenase (G6PD) deficiency
• Active clinically serious infection
• Uncontrolled hypertension
• Positive for HIV, or chronic Hepatitis B or C
• Subjects undergoing renal dialysis
• Known bleeding diathesis
• Ongoing substance abuse
• Pregnant or breast-feeding women