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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/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
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Scientific title
A Phase I, Multi-center, Open-label Study of LEE011 in Patients With Malignant Rhabdoid Tumors and Neuroblastoma
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Secondary ID [1]
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2012-004228-40
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Secondary ID [2]
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CLEE011X2102
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Malignant Rhabdoid Tumors (MRT)
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Neuroblastoma
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Condition category
Condition code
Cancer
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Neuroendocrine tumour (NET)
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Cancer
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Children's - Other
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Cancer
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Kidney
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - LEE011
Experimental: LEE011 -
Treatment: Drugs: LEE011
LEE011 is a small molecule inhibitor of CDK4/6.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Incidence Rate of Dose Limiting Toxicities (DLTs) by Primary System Organ Class, Preferred Term and Treatment
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Assessment method [1]
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A DLT was defined as an AE or clinically significant abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within the first 28 days of treatment with LEE011 and met any of the predefined criteria. For the purpose of dose-escalation decisions, DLTs were considered and included in the Bayesian Logistic Regression Model (BLRM). Patients who did not experience DLT during the first cycle were considered to have had sufficient safety evaluations if they were observed for = 28 days following the first dose and were considered to have had enough safety data to conclude that a DLT did not occur. Patients who did not meet these minimum safety evaluation requirements were regarded as ineligible for the DDS. A patient with multiple DLTs within a primary system organ class is counted only once in the total row.
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Timepoint [1]
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cycle 1 = 28 days (from the time of first dose)
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Secondary outcome [1]
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Overall Response Rate
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Assessment method [1]
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This analysis was not done as there were no responders.
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Timepoint [1]
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Every 2 cycles (cycle = 28 days) up to end of treatment, the maximum time a patient was on study was 1311 days
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Secondary outcome [2]
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Time to Disease Progression (TTP) Per RECIST 1.1
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Assessment method [2]
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TTP was assessed per Investigator, for the malignant rhabdoid tumor (MRT) & neuroblastoma patients for the pooled maximum tolerated dose (MTD) & recommended dose for expansion (RDE) according to RECIST 1.1 criteria using Kaplan-Meier method. Time to progression (TTP) is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to underlying cancer. If a patient had not had an event, time to progression was censored at the date of last adequate tumor assessment. At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
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Timepoint [2]
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Every 2 cycles (cycle = 28 days) up to end of treatment, the maximum time a patient was on study was 1311 days
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Secondary outcome [3]
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Duration of Response (DOR)
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Assessment method [3]
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Assess the anti-tumor activity of LEE011 by RECIST 1.1. DOR was not assessed.
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Timepoint [3]
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Every 2 cycles (cycle = 28 days) up to end of treatment, the maximum time a patient was on study was 1311 days
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Secondary outcome [4]
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Pharmacokinetics (PK) Parameter: AUC0-24
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Assessment method [4]
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The AUC calculated to the end of a dosing interval (tau) following single dose or at steady-state (amount x time x volume-1). PK parameters were estimated from individual plasma concentration-time profiles using noncompartmental methods in Phoenix WinNonlin.
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Timepoint [4]
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0,1, 2, 4, 8 hours post dose Cycle 1 Day 1 (C1D1) and Cycle 1 Day 15 (C1D15)
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Secondary outcome [5]
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Pharmacokinetics (PK) Parameter: Cmax
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Assessment method [5]
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Cmax is the maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration or at steady-state (mass x volume-1). PK parameters were estimated from individual plasma concentration-time profiles using noncompartmental methods in Phoenix WinNonlin
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Timepoint [5]
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C1D1, C1D15
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Secondary outcome [6]
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Pharmacokinetics (PK) Parameter: Tmax
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Assessment method [6]
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Tmax is the time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration or at steady-state (time). PK parameters were estimated from individual plasma concentration-time profiles using noncompartmental methods in Phoenix WinNonlin.
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Timepoint [6]
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C1D1, C1D15
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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.
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Minimum age
1
Year
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Maximum age
21
Years
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Sex
Both males and females
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Can healthy volunteers participate?
No
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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.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
N/A
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Single group
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Other design features
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Phase
Phase 1
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Terminated
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
28/05/2013
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
29/06/2017
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Sample size
Target
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Accrual to date
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Final
32
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Recruitment in Australia
Recruitment state(s)
WA
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Recruitment hospital [1]
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Novartis Investigative Site - Perth
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Recruitment postcode(s) [1]
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6840 - Perth
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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California
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Country [2]
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United States of America
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State/province [2]
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Georgia
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Country [3]
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United States of America
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State/province [3]
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Massachusetts
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Country [4]
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United States of America
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State/province [4]
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New York
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Country [5]
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United States of America
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State/province [5]
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Ohio
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Country [6]
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United States of America
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State/province [6]
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Tennessee
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Country [7]
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France
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State/province [7]
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Lyon Cedex
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Country [8]
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France
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State/province [8]
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Paris
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Country [9]
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France
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State/province [9]
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Villejuif Cedex
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Country [10]
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Germany
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State/province [10]
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Nordrhein-Westfalen
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Country [11]
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Germany
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State/province [11]
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Augsburg
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Country [12]
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United Kingdom
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State/province [12]
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Surrey
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Novartis Pharmaceuticals
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Address
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Country
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Ethics approval
Ethics application status
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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.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT01747876
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Novartis Pharmaceuticals
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Address
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Novartis Pharmaceuticals
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Country
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Phone
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Fax
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Email
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT01747876
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