This trial is active, not recruiting.

Condition malignant rhabdoid tumors (mrt), neuroblastoma
Treatment lee011
Phase phase 1
Target CDK4
Sponsor Novartis Pharmaceuticals
Start date May 2013
End date May 2017
Trial size 32 participants
Trial identifier NCT01747876, CLEE011X2102


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.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Intervention model single group assignment
Primary purpose treatment
Masking no masking
LEE011 is a small molecule inhibitor of CDK4/6.

Primary Outcomes

Incidence rate of dose limiting toxicities (DLTs)
time frame: cycle 1 = 28 days (from the time of first dose)

Secondary Outcomes

Number of patients with Adverse Events (AEs)
time frame: 18 months
Changes in laboratory values
time frame: baseline, 18 months
Changes in electrocardiograms (ECGs)
time frame: baseline, 18 months
Plasma concentration time profiles
time frame: 18 months
Pharmacokinetics (PK) parameters including but not limited to AUCtau, Cmax, Tmax, CL/F, accumulation ration (Racc) and T1/2, acc
time frame: 18 months
Overall response rate (ORR)
time frame: 18 months
Duration or response (DOR)
time frame: 18 months
Time to progression (TTP) per RECIST 1.1
time frame: 18 months
Number of patients with Serious Adverse Events (SAEs)
time frame: 18 months

Eligibility Criteria

All participants from 1 year up to 21 years old.

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.

Additional Information

Official title A Phase I, Multi-center, Open-label Study of LEE011 in Patients With Malignant Rhabdoid Tumors and Neuroblastoma
Trial information was received from ClinicalTrials.gov and was last updated in February 2017.
Information provided to ClinicalTrials.gov by Novartis.