Patient case: 45-year-old female with colon cancer; genetic feature: PIK3CA (E545K)

Clinical trial: 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

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?


Eligibility: 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

Relevance to patient case: not relevant