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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/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
N/A
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/ct2/show/NCT01742286
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/ct2/show/NCT01742286