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

• Status: Completed
• Trial end date: 2014-04-01
• Target enrollment: 0
• Participant gender: All

Summary

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?

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Bayer

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