Phase Ib Study of PI3(Phosphoinositol 3)-Kinase Inhibitor Copanlisib With MEK (Mitogen-activated Protein Kinase) Inhibitor Refametinib (BAY86-9766) in Patients With Advanced Cancer

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?


Eligibility Criteria:
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