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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01747876
First received: December 6, 2012
Last updated: September 9, 2014
Last verified: September 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: Allocation: Non-Randomized
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.


Enrollment: 32
Study Start Date: May 2013
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01747876

Locations
United States, California
University of California San Francisco Dept of Pediatic Oncology
San Francisco, California, United States, 94101
United States, Georgia
Children's Healthcare of Atlanta Dept of Oncology
Atlanta, Georgia, United States, 30342
United States, Massachusetts
Dana Farber Cancer Institute SC-7
Boston, Massachusetts, United States, 02115
United States, New York
Memorial Sloan Kettering Cancer Center Dept of Onc
New York, New York, United States, 10021
United States, Ohio
Cincinnati Children's Hospital Medical Center Dept of Oncology
Cincinnati, Ohio, United States, 45229-3039
United States, Tennessee
St. Jude's Children's Research Hospital Dept of Oncology
Memphis, Tennessee, United States, 38105-2794
Australia, Western Australia
Novartis Investigative Site
Perth, Western Australia, Australia
France
Novartis Investigative Site
Lyon Cedex, France, 69373
Novartis Investigative Site
Paris, France, 75231
Novartis Investigative Site
Villejuif Cedex, France, 94805
Germany
Novartis Investigative Site
Augsburg, Germany, 86156
Novartis Investigative Site
Köln, Germany, 50924
United Kingdom
Novartis Investigative Site
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: September 9, 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
Neoplasms
Rhabdoid Tumor
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Complex and Mixed

ClinicalTrials.gov processed this record on October 19, 2014