Study of Safety and Efficacy in Patients With Malignant Rhabdoid Tumors (MRT) and Neuroblastoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01747876
First received: December 6, 2012
Last updated: January 15, 2014
Last verified: January 2014

December 6, 2012
January 15, 2014
May 2013
May 2015   (final data collection date for primary outcome measure)
Incidence rate of dose limiting toxicities (DLTs) [ Time Frame: cycle 1 = 28 days (from the time of first dose) ] [ Designated as safety issue: Yes ]
Estimate the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) of LEE011 as a single agent
Incidence rate of dose limiting toxicities (DLTs) [ Time Frame: cycle 1 = 28 days (from the time of first dose) ] [ Designated as safety issue: Yes ]
Estimate the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) of LEE011 as a single agent when administered orally to patients with malignant rhabdoid tumors (MRTs) or neuroblastoma
Complete list of historical versions of study NCT01747876 on ClinicalTrials.gov Archive Site
  • Number of patients with Adverse Events (AEs) [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
    Characterize the safety and tolerability of LEE011.
  • Changes in laboratory values [ Time Frame: baseline, 18 months ] [ Designated as safety issue: Yes ]
    Characterize the safety and tolerability of LEE011.
  • Changes in electrocardiograms (ECGs) [ Time Frame: baseline, 18 months ] [ Designated as safety issue: Yes ]
    Characterize the safety and tolerability of LEE011.
  • Plasma concentration time profiles [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Characterize the PK of LEE001 and any clinically significant metabolites that may be identified.
  • Pharmacokinetics (PK) parameters including but not limited to AUCtau, Cmax, Tmax, CL/F, accumulation ration (Racc) and T1/2, acc [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Characterize the PK of LEE001 and any clinically significant metabolites that may be identified.
  • Overall response rate (ORR) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Assess the anti-tumor activity of LEE011 by RECIST 1.1. In addition, for neuroblastoma, response by International neuroblastoma response criteria (INRC), for primary Central nervous system (CNS) tumors, response by Revised Assessment in Neuro-Oncology (RANO) Criteria.
  • Duration or response (DOR) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Assess the anti-tumor activity of LEE011 by RECIST 1.1. In addition, for neuroblastoma, response by International neuroblastoma response criteria (INRC), for primary Central nervous system (CNS) tumors, response by Revised Assessment in Neuro-Oncology (RANO) Criteria.
  • Time to progression (TTP) per RECIST 1.1 [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Assess the anti-tumor activity of LEE011. TTP per RECIST 1.1. In addition, for neuroblastoma, response by International neuroblastoma response criteria (INRC), for primary Central nervous system (CNS) tumors, response by Revised Assessment in Neuro-Oncology (RANO) Criteria.
  • Number of patients with Serious Adverse Events (SAEs) [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
    Characterize the safety and tolerability of LEE011.
  • Number of patients with Adverse Events (AEs) [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
    Characterize the safety and tolerability of LEE011.
  • Changes in laboratory values [ Time Frame: baseline, 18 months ] [ Designated as safety issue: Yes ]
    Characterize the safety and tolerability of LEE011.
  • Changes in electrocardiograms (ECGs) [ Time Frame: baseline, 18 months ] [ Designated as safety issue: Yes ]
    Characterize the safety and tolerability of LEE011.
  • Plasma concentration time profiles [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Characterize the PK of LEE001 and any clinically significant metabolites that may be identified.
  • Pharmacokinetics (PK) parameters including but not limited to AUCtau, Cmax, Tmax, CL/F, accumulation ration (Racc) and T1/2, acc [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Characterize the PK of LEE001 and any clinically significant metabolites that may be identified.
  • Overall response rate (ORR) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Assess the anti-tumor activity of LEE011. In addition, for neuroblastoma, response by International neuroblastoma response criteria (INRC), for primary Central nervous system (CNS) tumors, response by Revised Assessment in Neuro-Oncology (RANO) Criteria.
  • Duration or response (DOR) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Assess the anti-tumor activity of LEE011. In addition, for neuroblastoma, response by International neuroblastoma response criteria (INRC), for primary Central nervous system (CNS) tumors, response by Revised Assessment in Neuro-Oncology (RANO) Criteria.
  • Time to progression (TTP) per RECIST 1.1 [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Assess the anti-tumor activity of LEE011. TTP per RECIST 1.1. In addition, for neuroblastoma, response by International neuroblastoma response criteria (INRC), for primary Central nervous system (CNS) tumors, response by Revised Assessment in Neuro-Oncology (RANO) Criteria.
  • Number of patients with Serious Adverse Events (SAEs) [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
    Characterize the safety and tolerability of LEE011.
Not Provided
Not Provided
 
Study of Safety and Efficacy in Patients With Malignant Rhabdoid Tumors (MRT) and Neuroblastoma
A Phase I, Multi-center, Open-label Study of LEE011 in Patients With Malignant Rhabdoid Tumors and Neuroblastoma

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.

Not Provided
Interventional
Phase 1
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Malignant Rhabdoid Tumors (MRT), Neuroblastoma
Drug: LEE011
LEE011 is a small molecule inhibitor of CDK4/6.
Experimental: LEE011
Intervention: Drug: LEE011
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
64
May 2015
May 2015   (final data collection date for primary outcome measure)

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.
Both
1 Year to 21 Years
No
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals
United States,   Australia,   Canada,   France,   Germany,   United Kingdom
 
NCT01747876
CLEE011X2102
No
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP