Phase Ib Study of PI3(Phosphoinositol 3)-Kinase Inhibitor BAY80-6946 With MEK (Mitogen-activated Protein Kinase) Inhibitor BAY86-9766 in Patients With Advanced Cancer

• Maximum Tolerated Dose [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
• Comparison of the BAY80-6946 AUC when given alone with the AUC when given with BAY86-9766 [ Time Frame: At day 15 ] [ Designated as safety issue: No ]
• Comparison of the BAY86-9766 AUC when given alone with the AUC when given with BAY80-6946 [ Time Frame: At day 15 ] [ Designated as safety issue: No ]

• Tumor Response as measured by RECIST 1.1 criteria [ Time Frame: 3 years ] [ Designated as safety issue: No ]
• Biomarker evaluation including analysis of pathway activation in blood and plasma [ Time Frame: 3 years ] [ Designated as safety issue: No ]
• Tumor Response as measured by FDG-PET at MTD and expansion cohort(s) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
• Pharmacodynamic biomarker evaluation analysis using paired tumor biopsies [ Time Frame: 3 years ] [ Designated as safety issue: No ]

• Tumor Response as measured by RECIST 1.1 criteria [ Time Frame: 2 years ] [ Designated as safety issue: No ]
• Biomarker evaluation including analysis of pathway activation in tumor tissue and blood/plasma [ Time Frame: 2 years ] [ Designated as safety issue: No ]

The PI3K (phosphoinositol 3-Kinase) inhibitor BAY80-6946 and the MEK (mitogen-activated protein kinase) inhibitor 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 BAY80-6946 and BAY86-9766 when given together at different/increasing dose levels?
2. What dose level of BAY80-6946 and BAY86-9766 should be tested in future clinical research studies?
3. How much BAY80-6946 is in the blood at specific times after administration and does adding BAY86-9766 have an affect?
4. How much BAY86-9766 is in the blood at specific times after administration and does adding BAY80-6946 have an affect?
5. Does the combination of BAY86-9766 and BAY80-6946 have an effect on tumors?

• Drug: BAY80-6946 + BAY86-9766
  BAY80-6946 will be administered as an IV infusion weekly for 3 weeks in combination with BAY86-9766 at varying dose levels. BAY86-9766 is administered orally twice a day starting at Day 4 of Cycle 1.
• Drug: BAY80-6946 + BAY86-9766
  BAY80-6946 will be administered as an IV infusion weekly in combination with BAY86-9766 at varying dose levels. BAY86-9766 is administered orally twice a day starting at Day 6 of Cycle 1 on a 4 day on, 3 day off schedule.

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