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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01747876




Registration number
NCT01747876
Ethics application status
Date submitted
6/12/2012
Date registered
12/12/2012
Date last updated
22/11/2019

Titles & IDs
Public title
Study of Safety and Efficacy in Patients With Malignant Rhabdoid Tumors (MRT) and Neuroblastoma
Scientific title
A Phase I, Multi-center, Open-label Study of LEE011 in Patients With Malignant Rhabdoid Tumors and Neuroblastoma
Secondary ID [1] 0 0
2012-004228-40
Secondary ID [2] 0 0
CLEE011X2102
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malignant Rhabdoid Tumors (MRT) 0 0
Neuroblastoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Neuroendocrine tumour (NET)
Cancer 0 0 0 0
Children's - Other
Cancer 0 0 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - LEE011

Experimental: LEE011 -


Treatment: Drugs: LEE011
LEE011 is a small molecule inhibitor of CDK4/6.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence Rate of Dose Limiting Toxicities (DLTs) by Primary System Organ Class, Preferred Term and Treatment
Timepoint [1] 0 0
cycle 1 = 28 days (from the time of first dose)
Secondary outcome [1] 0 0
Overall Response Rate
Timepoint [1] 0 0
Every 2 cycles (cycle = 28 days) up to end of treatment, the maximum time a patient was on study was 1311 days
Secondary outcome [2] 0 0
Time to Disease Progression (TTP) Per RECIST 1.1
Timepoint [2] 0 0
Every 2 cycles (cycle = 28 days) up to end of treatment, the maximum time a patient was on study was 1311 days
Secondary outcome [3] 0 0
Duration of Response (DOR)
Timepoint [3] 0 0
Every 2 cycles (cycle = 28 days) up to end of treatment, the maximum time a patient was on study was 1311 days
Secondary outcome [4] 0 0
Pharmacokinetics (PK) Parameter: AUC0-24
Timepoint [4] 0 0
0,1, 2, 4, 8 hours post dose Cycle 1 Day 1 (C1D1) and Cycle 1 Day 15 (C1D15)
Secondary outcome [5] 0 0
Pharmacokinetics (PK) Parameter: Cmax
Timepoint [5] 0 0
C1D1, C1D15
Secondary outcome [6] 0 0
Pharmacokinetics (PK) Parameter: Tmax
Timepoint [6] 0 0
C1D1, C1D15

Eligibility
Key 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.
Minimum age
1 Year
Maximum age
21 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
28/05/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
29/06/2017
Sample size
Target
Accrual to date
Final
32
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Novartis Investigative Site - Perth
Recruitment postcode(s) [1] 0 0
6840 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Ohio
Country [6] 0 0
United States of America
State/province [6] 0 0
Tennessee
Country [7] 0 0
France
State/province [7] 0 0
Lyon Cedex
Country [8] 0 0
France
State/province [8] 0 0
Paris
Country [9] 0 0
France
State/province [9] 0 0
Villejuif Cedex
Country [10] 0 0
Germany
State/province [10] 0 0
Nordrhein-Westfalen
Country [11] 0 0
Germany
State/province [11] 0 0
Augsburg
Country [12] 0 0
United Kingdom
State/province [12] 0 0
Surrey

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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 was 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 was also to have assessed the safety, tolerability, PK and preliminary evidence of antitumor activity of LEE011 in patients with MRT or neuroblastoma.
Trial website
https://clinicaltrials.gov/study/NCT01747876
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01747876