LEE011 is a small molecule inhibitor of CDK4/6. LEE011 has demonstrated in vitro and in vivo activity in both tumor models. The primary purpose of this study is to determine the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) in pediatric patients and to delineate a clinical dose to be used in future studies. This study will also assess the safety, tolerability, PK and preliminary evidence of antitumor activity of LEE011 in patients with MRT or neuroblastoma.
A Phase I, Multi-center, Open-label Study of LEE011 in Patients With Malignant Rhabdoid Tumors and Neuroblastoma
Confirmed diagnosis of MRT or, neuroblastoma or in dose escalation part, other tumors with documented evidence of D-cyclin-CDK4/6-INK4a-Rb pathway abnormalities (dose escalation part only),
Patients with CNS disease should be on stable doses of steroids for at least 7 days prior to first dose of LEE011 with no plans for escalation.
In expansion part, patients must have at least one measurable disease as defined by RECIST v1.1.
Patients must have a Lansky (≤ 16 years) or Karnofsky (> 16 years) score of at least 50.
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Prior history of QTc prolongation or QTcF> 450 ms on screening ECG.
Patients with the following laboratory values during screening:
Serum creatinine> 1.5 x upper limit of normal (ULN) for age
Total bilirubin>1.5 x ULN for age
Alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT)> 3 x ULN for age; aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase(SGOT)> 3 x ULN for age except in patients with tumor involvement of the liver who must have AST/SGOT and ALT/SGPT ≤ 5 x ULN for age. For the purpose of this study, the ULN for SGPT/ALT is 45 U/L.
Patients who are currently receiving treatment with agents that are metabolized predominantly through CYP3A4/5 and have a narrow therapeutic window and/or agents that are known strong inducers or inhibitors CYP3A4/5 are prohibited. In particular,enzyme-inducing antiepileptic drugs (EIAEDs).
Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for the study.
University of California San Francisco Dept of Pediatic Oncology San Francisco, California, 94101, USA
Children's Healthcare of Atlanta Dept of Oncology Atlanta, Georgia, 30342, USA
Dana Farber Cancer Institute SC-7 Boston, Massachusetts, 02215, USA
Memorial Sloan Kettering Cancer Center Dept of Onc NY, New York, 10065, USA
Cincinnati Children's Hospital Medical Center Dept of Oncology Cincinnati, Ohio, 45229, USA
St. Jude's Children's Research Hospital Dept of Oncology Memphis, Tennessee, 38105, USA
Novartis Investigative Site Perth, Western Australia, Australia
Novartis Investigative Site Lyon Cedex, 69373, France
Novartis Investigative Site Paris, 75231, France
Novartis Investigative Site Villejuif Cedex, 94805, France
Novartis Investigative Site Koeln, Nordrhein-Westfalen, 50937, Germany
Novartis Investigative Site Augsburg, 86156, Germany
Novartis Investigative Site Sutton, Surrey, SM2 5PT, United Kingdom