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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01742286




Registration number
NCT01742286
Ethics application status
Date submitted
30/11/2012
Date registered
5/12/2012
Date last updated
9/06/2020

Titles & IDs
Public title
Phase I Study of LDK378 in Pediatric, Malignancies With a Genetic Alteration in Anaplastic Lymphoma Kinase (ALK)
Scientific title
A Phase I, Open-label, Dose Escalation Study of LDK378 in Pediatric Patients With Malignancies That Have a Genetic Alteration in Anaplastic Lymphoma Kinase (ALK)
Secondary ID [1] 0 0
2012-002074-31
Secondary ID [2] 0 0
CLDK378X2103
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
ALK-activated Tumors 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

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

Experimental: LDK378 - All participants were administered a single-agent LDK378 (Ceritinib) orally, once daily, continuously in fasted or fed conditions.


Treatment: Drugs: Ceritinib
LDK378 is a capsule taken by mouth, contents can be mixed with food for pediatric patients or mixed with water and given via nasogastric/gastric (NG/G) tube. For patients in fasted group: 1-2 tablespoons (15-30 mL) of an appropriate food such as apple sauce or non-fat yogurt and a glass of water were allowed.

For patients in the fed cohort: LDK378 was taken with, or within 30 minutes after finishing a low-fat light snack containing 100-300 calories and 1.5-2 grams of fat.
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) Occurring During First Cycle of Treatment
Timepoint [1] 0 0
up to day 21 after the patient's first dose; cycle = within the first 21 days of patient's first dose
Secondary outcome [1] 0 0
Summary of Best Overall Response by Overall Response Rate (ORR) Per Investigator Assessment
Timepoint [1] 0 0
30 months
Secondary outcome [2] 0 0
Duration of Response (DoR) Per Investigator Assessment
Timepoint [2] 0 0
30 months
Secondary outcome [3] 0 0
Progression Free Survival (PFS) Based on Investigator Assessment
Timepoint [3] 0 0
30 months
Secondary outcome [4] 0 0
Plasma Concentration Time Profiles by Treatment Group in Escalation Phase
Timepoint [4] 0 0
0hr pre-dose, 2hrs post-dose, 4hrs post-dose, 6hrs post-dose & 24hrs post-dose in Cycle1 Day1 & Cycle 2 day 1; 0hr pre-dose in Cycle 1 Day 15, Cycle 2 Day1, Cycle 2 Day 2, Cycle 3 day 1 & Cycle 4 Day 1
Secondary outcome [5] 0 0
Plasma Concentration Time Profiles by Treatment Group in Expansion Phase
Timepoint [5] 0 0
0hr pre-dose Cycle 1 Day 1, cycle 1 Day 15; 0hr pre-dose, 2hrs post-dose, 4hrs post-dose, 6hrs post-dose & 24hrs post-dose in Cycle2 Day1; 0hr pre-dose in Cycle2 Day2, Cycle 3 Day 1 & Cycle 4 Day 1
Secondary outcome [6] 0 0
Pharmacokinetics (PK) Parameters: AUC0 - 24h & AUClast in Cycle 1 Day 1 - Dose Escalation Phase (Single Dose)
Timepoint [6] 0 0
0hr pre-dose, 2, 4, 6 & 24hrs post-dose
Secondary outcome [7] 0 0
Pharmacokinetics (PK) Parameters: AUC0 - 24h & AUClast in Cycle 2 Day 1 - Dose Escalation Phase (Single Dose)
Timepoint [7] 0 0
0hr pre-dose, 2, 4, 6 & 24hrs post-dose
Secondary outcome [8] 0 0
Pharmacokinetics (PK) Parameters: AUC0 - 24h & AUClast in Cycle 2 Day 1 - Dose Expansion Phase (Multiple Dose)
Timepoint [8] 0 0
0hr pre-dose, 2, 4, 6 & 24hrs post-dose
Secondary outcome [9] 0 0
PK Parameter: Cmax in Cycle 1 Day 1 - Dose Escalation Phase (Single Dose)
Timepoint [9] 0 0
0hr pre-dose, 2, 4, 6 & 24hrs post-dose
Secondary outcome [10] 0 0
PK Parameter: Cmax in Cycle 2 Day 1 - Dose Escalation Phase (Single Dose)
Timepoint [10] 0 0
0hr pre-dose, 2, 4, 6 & 24hrs post-dose
Secondary outcome [11] 0 0
PK Parameter: Cmax in Cycle 2 Day 1 - Dose Expansion Phase (Multiple Dose)
Timepoint [11] 0 0
0hr pre-dose, 2, 4, 6 & 24hrs post-dose
Secondary outcome [12] 0 0
PK Parameter: Tmax in Cycle 1 Day 1 - Dose Escalation Phase (Single Dose)
Timepoint [12] 0 0
0hr pre-dose, 2, 4, 6 & 24hrs post-dose
Secondary outcome [13] 0 0
PK Parameter: Tmax in Cycle 2 Day 1 - Dose Escalation Phase (Single Dose)
Timepoint [13] 0 0
0hr pre-dose, 2, 4, 6 & 24hrs post-dose
Secondary outcome [14] 0 0
PK Parameter: Tmax in Cycle 2 Day 1 - Dose Expansion Phase (Multiple Dose)
Timepoint [14] 0 0
0hr pre-dose, 2, 4, 6 & 24hrs post-dose
Secondary outcome [15] 0 0
PK Parameter: Racc in Dose Escalation Phase Cycle 2 Day 1
Timepoint [15] 0 0
0hr pre-dose, 2, 4, 6 & 24hrs post-dose

Eligibility
Key inclusion criteria
* Diagnosed with a locally advanced or metastatic malignancy that has progressed despite standard therapy, or for which no effective standard therapy exists
* Age = 12 months and < 18 years
* The tumor must carry a genetic alteration of ALK
* Patients must have evaluable or measurable disease.
* Karnofsky performance status score = 60% for patients > 12 years of age; Lansky score = 50% for patients = 12 years of age.
Minimum age
12 Months
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

* Symptomatic central nervous system (CNS) metastases who are neurologically unstable or require increasing doses of steroids or local CNS-directed therapy (such as radiotherapy, surgery or intrathecal chemotherapy) to control their CNS disease
* Inadequate end organ function as defined by specified laboratory values
* Body surface area (BSA) < 0.35 m2
* Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of LDK378 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome)
* Use of medications that are known to be strong inhibitors or inducers of CYP3A4/5 that cannot be discontinued at least 1 week prior to start of treatment with LDK378 and for the duration of the study
* Use of medications that are mainly metabolized by CYP3A4/5 or CYP2C9 that cannot be discontinued at least 1 week prior to start of treatment with LDK378 and for the duration of the study
* History of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis
* History of pancreatitis or history of increased amylase or lipase that was due to pancreatic disease.
* Medications with a known risk of prolongation of QT interval

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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
28/08/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
26/04/2019
Sample size
Target
Accrual to date
Final
83
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Randwick
Recruitment hospital [2] 0 0
Novartis Investigative Site - Parkville
Recruitment postcode(s) [1] 0 0
2130 - Randwick
Recruitment postcode(s) [2] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Massachusetts
Country [2] 0 0
United States of America
State/province [2] 0 0
New York
Country [3] 0 0
United States of America
State/province [3] 0 0
Ohio
Country [4] 0 0
United States of America
State/province [4] 0 0
Tennessee
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
Canada
State/province [6] 0 0
Ontario
Country [7] 0 0
France
State/province [7] 0 0
Paris
Country [8] 0 0
France
State/province [8] 0 0
Villejuif Cedex
Country [9] 0 0
Germany
State/province [9] 0 0
Nordrhein-Westfalen
Country [10] 0 0
Germany
State/province [10] 0 0
Berlin
Country [11] 0 0
Germany
State/province [11] 0 0
Essen
Country [12] 0 0
Italy
State/province [12] 0 0
MI
Country [13] 0 0
Korea, Republic of
State/province [13] 0 0
Seoul
Country [14] 0 0
Netherlands
State/province [14] 0 0
CS
Country [15] 0 0
Netherlands
State/province [15] 0 0
Amsterdam
Country [16] 0 0
Netherlands
State/province [16] 0 0
Rotterdam
Country [17] 0 0
Spain
State/province [17] 0 0
Catalunya
Country [18] 0 0
Spain
State/province [18] 0 0
Comunidad Valenciana
Country [19] 0 0
Spain
State/province [19] 0 0
Madrid
Country [20] 0 0
United Kingdom
State/province [20] 0 0
Birmingham
Country [21] 0 0
United Kingdom
State/province [21] 0 0
Surrey

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

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study was to estimate the maximum tolerated dose and/or recommended dose for expansion of LDK378 as a single agent, assess safety, tolerability and anti-tumor activity and characterize single and multiple-dose pharmacokinetics when administered orally to pediatric patients with ALK-activated tumors, with and without food.
Trial website
https://clinicaltrials.gov/study/NCT01742286
Trial related presentations / publications
Fischer M, Moreno L, Ziegler DS, Marshall LV, Zwaan CM, Irwin MS, Casanova M, Sabado C, Wulff B, Stegert M, Wang L, Hurtado FK, Branle F, Geoerger B, Schulte JH. Ceritinib in paediatric patients with anaplastic lymphoma kinase-positive malignancies: an open-label, multicentre, phase 1, dose-escalation and dose-expansion study. Lancet Oncol. 2021 Dec;22(12):1764-1776. doi: 10.1016/S1470-2045(21)00536-2. Epub 2021 Nov 12.
Brivio E, Zwaan CM. ALK inhibition in two emblematic cases of pediatric inflammatory myofibroblastic tumor: Efficacy and side effects. Pediatr Blood Cancer. 2019 May;66(5):e27645. doi: 10.1002/pbc.27645. Epub 2019 Jan 29.
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/NCT01742286