LEE011 is a new oral drug designed to inhibit the activity of an enzyme known as CDK4/6. CDK4/6 is involved in the process that allows both normal and cancer cells to divide and multiply. Cancer cells are often driven to divide and multiply by abnormalities that increase the activity of CDK4. Hence there is hope that blocking the activity of CDK4 may slow the growth of some cancers. LEE011 has shown anti-cancer activity in several different tumor models in animals. Because CDK4 is important in both normal and cancerous cells, LEE011 is expected to decrease the ability of the bone marrow to make white blood cells, platelets, and red blood cells. Although these effects are expected to be reversible, they can increase the risk of infection, bleeding and fatigue. The primary purpose of this study is to find the highest dose of LEE011 that can be safely given to adult patients with advanced solid tumors or lymphomas for which no further effective standard treatment is available. It will provide information about the side effects that may occur following treatment. The study will also possibly provide early evidence for LEE011's anti-tumor activity.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
156
Dana Farber Cancer Institute DFCI
Boston, Massachusetts, United States
University of Michigan Comprehensive Cancer Center SC
Ann Arbor, Michigan, United States
Memorial Sloan Kettering MSKCC (2)
New York, New York, United States
Sarah Cannon Research Institute DeptofSarahCannonRes.Inst. (2)
Nashville, Tennessee, United States
Novartis Investigative Site
Lyon, France
Novartis Investigative Site
Villejuif, France
Novartis Investigative Site
Utrecht, Netherlands
Primary Outcome Measures: Maximum tolerated dose of LEE011 when administered orally once daily, as assessed by Frequency of DLTs as a function of LEE011 dose
Time frame: 12 month
Safety and tolerability of LEE011, as assessed by grade and frequency of Adverse events, serious adverse events, and changes in lab values, vital signs and ECGs.
Time frame: 18 months
The pharmacokinetics (PK) of LEE011 (AUC inf, Cmax, Tmax, T1/2)
Time frame: 18 months
Any pharmacodynamic activity of LEE011 treatment, as assessed by changes from baseline in biomarkers associated with the pharmacologic activity of LEE011
Time frame: 18 months
Antitumor activity that may be associated with LEE011 treatment, as assessed by CT/MRI Response Evaluation Criteria for Solid Tumors (RECIST) Criteria v1.0 or Cheson Criteria 2007 for lymphomas.
Time frame: 18 months
Relationship between QTc prolongation and exposure to LEE011 and/or any of its relevant metabolites.
Time frame: 18 months
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