Study of Safety and Efficacy in Patients With Malignant Rhabdoid Tumors (MRT) and Neuroblastoma
Condition: Malignant Rhabdoid Tumors (MRT); Neuroblastoma
MeSH terms: Neuroblastoma; Rhabdoid Tumor
Intervention: LEE011
Intervention description: LEE011 is a small molecule inhibitor of CDK4/6.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: All
Minimum age: 1 Year
Maximum age: 21 Years
Healthy volunteers: No
Keywords: LEE011; Phase 1; pediatric; CDK4/6 inhibitor; dose escalation; malignant rhabdoid tumors; MRT; neuroblastoma

Summary:

      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 was 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 was also to have assessed
      the safety, tolerability, PK and preliminary evidence of antitumor activity of LEE011 in
      patients with MRT or neuroblastoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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.

        Exclusion Criteria:

          -  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.