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

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase I, Multi-center, Open-label Study of LEE011 in Patients With Malignant Rhabdoid Tumors and Neuroblastoma

Brief 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 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.


Detailed Summary:
Sponsor: Novartis Pharmaceuticals

Current Primary Outcome: Incidence rate of dose limiting toxicities (DLTs) [ Time Frame: cycle 1 = 28 days (from the time of first dose) ]

Estimate the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) of LEE011 as a single agent


Original Primary Outcome: Incidence rate of dose limiting toxicities (DLTs) [ Time Frame: cycle 1 = 28 days (from the time of first dose) ]

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


Current Secondary Outcome:

  • Number of patients with Adverse Events (AEs) [ Time Frame: 18 months ]
    Characterize the safety and tolerability of LEE011.
  • Changes in laboratory values [ Time Frame: baseline, 18 months ]
    Characterize the safety and tolerability of LEE011.
  • Changes in electrocardiograms (ECGs) [ Time Frame: baseline, 18 months ]
    Characterize the safety and tolerability of LEE011.
  • Plasma concentration time profiles [ Time Frame: 18 months ]
    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 ]
    Characterize the PK of LEE001 and any clinically significant metabolites that may be identified.
  • Overall response rate (ORR) [ Time Frame: 18 months ]
    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 ]
    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 ]
    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 ]
    Characterize the safety and tolerability of LEE011.


Original Secondary Outcome:

  • Number of patients with Adverse Events (AEs) [ Time Frame: 18 months ]
    Characterize the safety and tolerability of LEE011.
  • Changes in laboratory values [ Time Frame: baseline, 18 months ]
    Characterize the safety and tolerability of LEE011.
  • Changes in electrocardiograms (ECGs) [ Time Frame: baseline, 18 months ]
    Characterize the safety and tolerability of LEE011.
  • Plasma concentration time profiles [ Time Frame: 18 months ]
    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 ]
    Characterize the PK of LEE001 and any clinically significant metabolites that may be identified.
  • Overall response rate (ORR) [ Time Frame: 18 months ]
    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 ]
    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 ]
    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 ]
    Characterize the safety and tolerability of LEE011.


Information By: Novartis

Dates:
Date Received: December 6, 2012
Date Started: May 28, 2013
Date Completion: June 19, 2017
Last Updated: May 15, 2017
Last Verified: May 2017