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

This study is currently recruiting participants.
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
  Purpose

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.


Condition Intervention Phase
Malignant Rhabdoid Tumors (MRT), Neuroblastoma
Drug: LEE011
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I, Multi-center, Open-label Study of LEE011 in Patients With Malignant Rhabdoid Tumors and Neuroblastoma

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 64
Study Start Date: May 2013
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LEE011 Drug: LEE011
LEE011 is a small molecule inhibitor of CDK4/6.

  Eligibility

Ages Eligible for Study:   1 Year to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01747876

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals

Locations
United States, California
University of California San Francisco Dept of Pediatic Oncology Recruiting
San Francisco, California, United States, 94101
Contact: Sharon Kresge    415-514-3658    Sharon.Kresge@ucsf.edu   
Principal Investigator: Steven Dubois         
United States, Georgia
Children's Healthcare of Atlanta Dept of Oncology Recruiting
Atlanta, Georgia, United States, 30342
Contact: Katherine Garrett    404-785-3535    katherine.garrett@choa.org   
Principal Investigator: Muna Qayed         
United States, Massachusetts
Dana Farber Cancer Institute SC-7 Recruiting
Boston, Massachusetts, United States, 02115
Contact: Nathan Pinches    617-632-6308    nathan_pinches@dfci.harvard.edu   
Principal Investigator: Susan Chi         
United States, New York
Memorial Sloan Kettering Cancer Center Dept of Onc Not yet recruiting
New York, New York, United States, 10021
Contact: Elizabeth Chamberlain    646-888-5716    chambee1@mskcc.org   
Principal Investigator: Shakeel Modak         
United States, Ohio
Cincinnati Children's Hospital Medical Center Dept of Oncology Recruiting
Cincinnati, Ohio, United States, 45229-3039
Contact: Jenny T Thomas    513-636-9419    jenny.quinn@cchmc.org   
Principal Investigator: James Geller         
United States, Pennsylvania
Children's Hospital of Philadelphia Dept of Oncology Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104-4399
Contact: Devaney Camburn    267-426-9293    camburnd@email.chop.edu   
Principal Investigator: John Maris         
United States, Tennessee
St. Jude's Children's Research Hospital Dept of Oncology Not yet recruiting
Memphis, Tennessee, United States, 38105-2794
Contact: Jennifer Vest    901-595-2734    jennifer.vest@stjude.org   
Principal Investigator: Giles Robinson         
United States, Washington
Seattle Cancer Care Alliance/Fred Hutchinson Cancer Research Dept Oncology Not yet recruiting
Seattle, Washington, United States, 98109-1023
Contact: Dione Froman    206-884-1214    dione.froman@seattlechildrens.org   
Principal Investigator: Julie Park         
Australia, New South Wales
Novartis Investigative Site Withdrawn
Randwick, New South Wales, Australia, 2130
Australia, Victoria
Novartis Investigative Site Not yet recruiting
Parkville, Victoria, Australia, 3052
Australia, Western Australia
Novartis Investigative Site Not yet recruiting
Perth, Western Australia, Australia
Canada, Ontario
Novartis Investigative Site Withdrawn
Toronto, Ontario, Canada, M5G 1X8
France
Novartis Investigative Site Recruiting
Lyon Cedex, France, 69373
Novartis Investigative Site Recruiting
Paris, France, 75231
Novartis Investigative Site Recruiting
Villejuif Cedex, France, 94805
Germany
Novartis Investigative Site Not yet recruiting
Augsburg, Germany, 86156
Novartis Investigative Site Not yet recruiting
Köln, Germany, 50924
United Kingdom
Novartis Investigative Site Recruiting
Sutton, Surrey, United Kingdom, SM2 5PT
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01747876     History of Changes
Other Study ID Numbers: CLEE011X2102
Study First Received: December 6, 2012
Last Updated: January 15, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
Phase 1
pediatric
CDK4/6 inhibitor
dose escalation
malignant rhabdoid tumors
MRT
neuroblastoma

Additional relevant MeSH terms:
Neuroblastoma
Rhabdoid Tumor
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Complex and Mixed

ClinicalTrials.gov processed this record on April 17, 2014