NCT01742286

Phase I Study of LDK378 in Pediatric, Malignancies With a Genetic Alteration in Anaplastic Lymphoma Kinase (ALK)

Completed Phase 1 Results posted Last updated 9 June 2020

What this trial tests

Phase 1 trial testing Ceritinib in ALK-activated Tumors in 83 participants. Completed in 26 April 2019.

Timeline

28 August 2013

Primary endpoint
26 April 2019

26 April 2019

Quick facts

Lead sponsor	Novartis Pharmaceuticals
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	83
Start date	28 August 2013
Primary completion	26 April 2019
Estimated completion	26 April 2019
Sites	23 locations across France, Italy, Netherlands, United Kingdom, Germany, South Korea, Canada, Australia

Drugs / interventions tested

• Ceritinib (ceritinib) — full drug profile →

Conditions studied

• ALK-activated Tumors — all drugs for ALK-activated Tumors →

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

Adults 12 Months to 17, any sex, with ALK-activated Tumors. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Incidence Rate of Dose Limiting Toxicities (DLTs) Occurring During First Cycle of Treatment Primary · up to day 21 after the patient's first dose; cycle = within the first 21 days of patient's first dose

A DLT is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant therapies that occurs within the first 21 days of treatment with LDK378 and meets a specified defined criteria. A participant with multiple occurrences of DLTs under one treatment is counted only once in the Adverse Event category for that treatment. A participant with multiple DLTs within a primary system organ class is counted only once in the total row.

Investigations: Alanine aminotransferase incr.

Group	Value	95% CI
Fasted: Ceritinib 300 mg/m2	0
Fasted: Ceritinib 450 mg/m2	0
Fasted: Ceritinib 510 mg/m2	0
Fasted: Ceritinib 560 mg/m2	1
Fed: Ceritinib 320 mg/m2	0
Fed: Ceritinib 400 mg/m2	1
Fed: Ceritinib 500 mg/m2	0

Gastrointestinal disorders: abdominal pain

Group	Value	95% CI
Fasted: Ceritinib 300 mg/m2	0
Fasted: Ceritinib 450 mg/m2	0
Fasted: Ceritinib 510 mg/m2	0
Fasted: Ceritinib 560 mg/m2	1
Fed: Ceritinib 320 mg/m2	0
Fed: Ceritinib 400 mg/m2	0
Fed: Ceritinib 500 mg/m2	0

Gastrointestinal disorders: Influenza

Group	Value	95% CI
Fasted: Ceritinib 300 mg/m2	0
Fasted: Ceritinib 450 mg/m2	0
Fasted: Ceritinib 510 mg/m2	0
Fasted: Ceritinib 560 mg/m2	0
Fed: Ceritinib 320 mg/m2	0
Fed: Ceritinib 400 mg/m2	0
Fed: Ceritinib 500 mg/m2	1

Total DLTs

Group	Value	95% CI
Fasted: Ceritinib 300 mg/m2	0
Fasted: Ceritinib 450 mg/m2	0
Fasted: Ceritinib 510 mg/m2	0
Fasted: Ceritinib 560 mg/m2	2
Fed: Ceritinib 320 mg/m2	0
Fed: Ceritinib 400 mg/m2	1
Fed: Ceritinib 500 mg/m2	1

Summary of Best Overall Response by Overall Response Rate (ORR) Per Investigator Assessment Secondary · 30 months

ORR is the percentage of participants with a best overall response of complete response (CR) or partial response (PR). ORR was assessed per Investigator as per RECIST 1.1 in participants with neuroblastoma and other solid tumors, and by International Working Group (IWG) criteria in patients with lymphoma. Per RECIST 1.1 (for neuroblastoma \& other solid tumors): CR: disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. PR: at least a 30% decrease in the sum of diameter of all target l

Group	Value	95% CI
ALK-activated Neuroblastoma	20.0	7.7 – 38.6
ALK-activated Inflammatory Myofibroblastic Tumors (IMT)	70.0	34.8 – 93.3
ALK-activated Anaplastic Large Cell Lymphoma (ALCL)	75.0	34.9 – 96.8
ALK-activated Other	14.3	0.4 – 57.9

Duration of Response (DoR) Per Investigator Assessment Secondary · 30 months

DOR is defined as the time from first documented response (PR or CR) to the date of first documented disease progression (PD) or death due to any cause. DOR was assessed per Investigator as per RECIST 1.1 in participants with neuroblastoma and other solid tumors, and by International Working Group (IWG) criteria in patients with lymphoma. Per RECIST 1.1 (for neuroblastoma \& other solid tumors): CR: disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. PR: at least a 30% decrease in t

Group	Value	95% CI
ALK-activated Neuroblastoma	15.0	5.8 – 22.2
ALK-activated Inflammatory Myofibroblastic Tumors (IMT)	NA	3.5 – NA
ALK-activated Anaplastic Large Cell Lymphoma (ALCL)	NA	2.8 – NA
ALK-activated Other	NA	NA – NA

Progression Free Survival (PFS) Based on Investigator Assessment Secondary · 30 months

PFS 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 any cause. PFS was assessed per Investigator as per RECIST 1.1 in participants with neuroblastoma and other solid tumors, and by International Working Group (IWG) criteria in patients with lymphoma. Per RECIST 1.1 (for neuroblastoma \& other solid tumors): CR: disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm. PR: at least a 30% decrease in

Group	Value	95% CI
ALK-activated Neuroblastoma	2.4	1.2 – 6.8
ALK-activated Inflammatory Myofibroblastic Tumors (IMT)	NA	1.2 – NA
ALK-activated Anaplastic Large Cell Lymphoma (ALCL)	NA	4.1 – NA
ALK-activated Other	1.9	1.2 – NA

Plasma Concentration Time Profiles by Treatment Group in Escalation Phase Secondary · 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

Characterize single and multiple-dose PK of LDK378 in pediatric patients. Only PK plasma concentrations with non-missing sampling date and time, and for which the last dose date and time prior to the PK sample draw are non-missing, were included in the PK analysis.

Cycle1 Day1 (C1D1) 0 hr pre-dose

Group	Value	95% CI
Fasted: Ceritinib 300 mg/m2	0.0	± 0.0
Fasted: Ceritinib 450 mg/m2	0.0	± 0.0
Fasted: Ceritinib 510 mg/m2	0.0	± 0.0
Fasted: Ceritinib 560 mg/m2	0.0	± 0.0
Fed: Ceritinib 320 mg/m2	0.0	± 0.0
Fed: Ceritinib 400 mg/m2	0.0	± 0.0
Fed: Ceritinib 500 mg/m2	0.0	± 0.0

C1D1 2 hrs post-dose

Group	Value	95% CI
Fasted: Ceritinib 300 mg/m2	104	± 97.9
Fasted: Ceritinib 450 mg/m2	99.0	± 94.7
Fasted: Ceritinib 510 mg/m2	112	± 90.6
Fasted: Ceritinib 560 mg/m2	126	± 0.6
Fed: Ceritinib 320 mg/m2	52.4	± 138.1
Fed: Ceritinib 400 mg/m2	197	± 58.3
Fed: Ceritinib 500 mg/m2	72.5	± 82.3

C1D1 4 hrs post-dose

Group	Value	95% CI
Fasted: Ceritinib 300 mg/m2	216	± 39.6
Fasted: Ceritinib 450 mg/m2	233	± 69.0
Fasted: Ceritinib 510 mg/m2	250	± 93.5
Fasted: Ceritinib 560 mg/m2	350	± 54.7
Fed: Ceritinib 320 mg/m2	166	± 92.8
Fed: Ceritinib 400 mg/m2	311	± 28.1
Fed: Ceritinib 500 mg/m2	153	± 34.1

C1D1 6 hrs post-dose

Group	Value	95% CI
Fasted: Ceritinib 300 mg/m2	227	± 33.8
Fasted: Ceritinib 450 mg/m2	245	± 78.1
Fasted: Ceritinib 510 mg/m2	245	± 97.2
Fasted: Ceritinib 560 mg/m2	423	± 74.2
Fed: Ceritinib 320 mg/m2	275	± 35.3
Fed: Ceritinib 400 mg/m2	318	± 36.7
Fed: Ceritinib 500 mg/m2	168	± 68.9

C1D1 24 hrs post-dose

Group	Value	95% CI
Fasted: Ceritinib 300 mg/m2	130	± 66.3
Fasted: Ceritinib 450 mg/m2	141	± 89.9
Fasted: Ceritinib 510 mg/m2	86.4	± 117.2
Fasted: Ceritinib 560 mg/m2	268	± 73.6
Fed: Ceritinib 320 mg/m2	98.5	± 63.7
Fed: Ceritinib 400 mg/m2	126	± 107.7
Fed: Ceritinib 500 mg/m2	161	± 111.3

C1D2 0 hr pre-dose

Group	Value	95% CI
Fasted: Ceritinib 300 mg/m2	130	± 66.3
Fasted: Ceritinib 450 mg/m2	141	± 89.9
Fasted: Ceritinib 510 mg/m2	86.4	± 117.2
Fasted: Ceritinib 560 mg/m2	268	± 73.6
Fed: Ceritinib 320 mg/m2	98.5	± 63.7
Fed: Ceritinib 400 mg/m2	126	± 107.7
Fed: Ceritinib 500 mg/m2	161	± 111.3

C1D15 0 hr pre-dose

Group	Value	95% CI
Fasted: Ceritinib 300 mg/m2	193	± 99.6
Fasted: Ceritinib 450 mg/m2	618	± 64.6
Fasted: Ceritinib 510 mg/m2	537	± 49.9
Fasted: Ceritinib 560 mg/m2	942	± 5.1
Fed: Ceritinib 320 mg/m2	262	± 118.4
Fed: Ceritinib 400 mg/m2	379	± 119.2
Fed: Ceritinib 500 mg/m2	461	± 76.3

C2D1 0 hr pre-dose

Group	Value	95% CI
Fasted: Ceritinib 300 mg/m2	169	± 299.5
Fasted: Ceritinib 450 mg/m2	661	± 53.5
Fasted: Ceritinib 510 mg/m2	672	± 45.4
Fasted: Ceritinib 560 mg/m2	695	± 152.7
Fed: Ceritinib 320 mg/m2	218	± 103.7
Fed: Ceritinib 400 mg/m2	429	± 73.8
Fed: Ceritinib 500 mg/m2	655	± 12.4

Plasma Concentration Time Profiles by Treatment Group in Expansion Phase Secondary · 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

Characterize single and multiple-dose PK of LDK378 in pediatric patients. Only PK plasma concentrations with non-missing sampling date and time, and for which the last dose date and time prior to the PK sample draw are non-missing, were included in the PK analysis.

C1D1 0 hr pre-dose

Group	Value	95% CI
Fasted: Ceritinib 510 mg/m2	0.0	± 0.0
Fed: Ceritinib 500 mg/m2	0.0	± 0.0

C1D15 0 hr post-dose

Group	Value	95% CI
Fasted: Ceritinib 510 mg/m2	1190	± 0.0

C2D1 0 hr pre-dose

Group	Value	95% CI
Fasted: Ceritinib 510 mg/m2	529	± 365.4
Fed: Ceritinib 500 mg/m2	627	± 93.6

C2D1 2 hrs post-dose

Group	Value	95% CI
Fasted: Ceritinib 510 mg/m2	798	± 69.0
Fed: Ceritinib 500 mg/m2	729	± 72.3

C2D1 4 hrs post-dose

Group	Value	95% CI
Fasted: Ceritinib 510 mg/m2	863	± 65.2
Fed: Ceritinib 500 mg/m2	828	± 47.9

C2D1 6 hrs post-dose

Group	Value	95% CI
Fasted: Ceritinib 510 mg/m2	939	± 71.4
Fed: Ceritinib 500 mg/m2	870	± 52.6

C2D1 24 hrs post-dose

Group	Value	95% CI
Fasted: Ceritinib 510 mg/m2	615	± 119.9
Fed: Ceritinib 500 mg/m2	596	± 75.5

C2D2 0 hr pre-dose

Group	Value	95% CI
Fasted: Ceritinib 510 mg/m2	615	± 119.9
Fed: Ceritinib 500 mg/m2	596	± 75.5

Pharmacokinetics (PK) Parameters: AUC0 - 24h & AUClast in Cycle 1 Day 1 - Dose Escalation Phase (Single Dose) Secondary · 0hr pre-dose, 2, 4, 6 & 24hrs post-dose

Characterize single and multiple-dose PK of LDK378 in pediatric patients. AUC: Area under the plasma (serum, or blood) concentration versus time curve AUClast: Area under the concentration-time curve from time zero to the last measureable concentration time AUC0-24h: Area under the plasma concentration-time curve t=0-24 h

AUC0-24h

Group	Value	95% CI
Fasted: Ceritinib 300 mg/m2	3920	± 39.9
Fasted: Ceritinib 450 mg/m2	5220	± 58.0
Fasted: Ceritinib 510 mg/m2	8750	± 11.1
Fed: Ceritinib 320 mg/m2	5720	± 0.0
Fed: Ceritinib 400 mg/m2	7272	± 0.0
Fed: Ceritinib 500 mg/m2	4730	± 59.4

AUClast

Group	Value	95% CI
Fasted: Ceritinib 300 mg/m2	4260	± 39.3
Fasted: Ceritinib 450 mg/m2	4350	± 91.8
Fasted: Ceritinib 510 mg/m2	7670	± 24.5
Fasted: Ceritinib 560 mg/m2	4860	± 0.0
Fed: Ceritinib 320 mg/m2	3730	± 48.6
Fed: Ceritinib 400 mg/m2	5760	± 49.1
Fed: Ceritinib 500 mg/m2	4940	± 32.6

Pharmacokinetics (PK) Parameters: AUC0 - 24h & AUClast in Cycle 2 Day 1 - Dose Escalation Phase (Single Dose) Secondary · 0hr pre-dose, 2, 4, 6 & 24hrs post-dose

Characterize single and multiple-dose PK of LDK378 in pediatric patients. AUC: Area under the plasma (serum, or blood) concentration versus time curve AUClast: Area under the concentration-time curve from time zero to the last measureable concentration time; AUC0-24h: Area under the plasma concentration-time curve t=0-24 h

AUC0-24h

Group	Value	95% CI
Fasted: Ceritinib 300 mg/m2	8160	± 44.0
Fasted: Ceritinib 450 mg/m2	16900	± 59.1
Fasted: Ceritinib 510 mg/m2	21000	± 20.8
Fasted: Ceritinib 560 mg/m2	25300	± 39.2
Fed: Ceritinib 320 mg/m2	2100	± 0.0
Fed: Ceritinib 400 mg/m2	30500	± 0.0
Fed: Ceritinib 500 mg/m2	16500	± 0.0

AUClast

Group	Value	95% CI
Fasted: Ceritinib 300 mg/m2	8210	± 44.3
Fasted: Ceritinib 450 mg/m2	18000	± 50.0
Fasted: Ceritinib 510 mg/m2	17200	± 51.2
Fasted: Ceritinib 560 mg/m2	25600	± 39.0
Fed: Ceritinib 320 mg/m2	5840	± 118.4
Fed: Ceritinib 400 mg/m2	125000	± 113.2
Fed: Ceritinib 500 mg/m2	16700	± 1.8

Pharmacokinetics (PK) Parameters: AUC0 - 24h & AUClast in Cycle 2 Day 1 - Dose Expansion Phase (Multiple Dose) Secondary · 0hr pre-dose, 2, 4, 6 & 24hrs post-dose

Characterize single and multiple-dose PK of LDK378 in pediatric patients. In this phase ceritinib was expanded at 500mg/m2 fed and 510mg/m2 fasted administered orally once daily and was assessed only at steady state, Cycle 2 Day 1. AUC: Area under the plasma (serum, or blood) concentration versus time curve AUClast: Area under the plasma (serum, or blood) concentration versus time curverea under the concentration-time curve from time zero to the last measureable concentration time AUC0-24h: Area under the plasma concentration-time curve t=0-24 h

AUC0-24h

Group	Value	95% CI
Fed: Ceritinib 500 mg/m2	15900	± 93.8

AUClast

Group	Value	95% CI
Fasted: Ceritinib 510 mg/m2	24100	± 38.9
Fed: Ceritinib 500 mg/m2	16100	± 61.2

PK Parameter: Cmax in Cycle 1 Day 1 - Dose Escalation Phase (Single Dose) Secondary · 0hr pre-dose, 2, 4, 6 & 24hrs post-dose

Characterize single and multiple-dose PK of LDK378 in pediatric patients. Cmax: Maximum (peak) concentration of drug

Group	Value	95% CI
Fasted: Ceritinib 300 mg/m2	258	± 39.0
Fasted: Ceritinib 450 mg/m2	270	± 82.1
Fasted: Ceritinib 510 mg/m2	537	± 22.2
Fasted: Ceritinib 560 mg/m2	265	± 0.0
Fed: Ceritinib 320 mg/m2	251	± 37.0
Fed: Ceritinib 400 mg/m2	341	± 34.2
Fed: Ceritinib 500 mg/m2	204	± 54.6

PK Parameter: Cmax in Cycle 2 Day 1 - Dose Escalation Phase (Single Dose) Secondary · 0hr pre-dose, 2, 4, 6 & 24hrs post-dose

Characterize single and multiple-dose PK of LDK378 in pediatric patients. Cmax: Maximum (peak) concentration of drug.

Group	Value	95% CI
Fasted: Ceritinib 300 mg/m2	427	± 38.5
Fasted: Ceritinib 450 mg/m2	870	± 48.7
Fasted: Ceritinib 510 mg/m2	1020	± 32.1
Fasted: Ceritinib 560 mg/m2	1300	± 21.4
Fed: Ceritinib 320 mg/m2	300	± 130.3
Fed: Ceritinib 400 mg/m2	674	± 93.8
Fed: Ceritinib 500 mg/m2	804	± 10.4

PK Parameter: Cmax in Cycle 2 Day 1 - Dose Expansion Phase (Multiple Dose) Secondary · 0hr pre-dose, 2, 4, 6 & 24hrs post-dose

Characterize single and multiple-dose PK of LDK378 in pediatric patients. In this phase ceritinib was expanded at 500mg/m2 fed and 510mg/m2 fasted administered orally once daily and was assessed only at steady state, Cycle 2 Day 1. Cmax: Maximum (peak) concentration of drug

Group	Value	95% CI
Fasted: Ceritinib 510 mg/m2	1220	± 40.2
Fed: Ceritinib 500 mg/m2	890	± 50.9

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events (AEs) were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, up to maximum duration of 63.7 months.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Fasted Ceritinib 300mg/m2

Serious: 1/5 (20%)

Deaths: 1/5

Fasted Ceritinib 450mg/m2

Serious: 4/12 (33%)

Deaths: 1/12

Fasted Ceritinib 510mg/m2

Serious: 8/13 (62%)

Deaths: 2/13

Fasted Ceritinib 560mg/m2

Serious: 2/2 (100%)

Deaths: 0/2

Fed Ceritinib 320mg/m2

Serious: 3/4 (75%)

Deaths: 2/4

Fed Ceritinib 400mg/m2

Serious: 1/5 (20%)

Deaths: 1/5

Fed Ceritinib 500mg/m2

Serious: 21/42 (50%)

Deaths: 5/42

Fasted+Fed All Patients

Serious: 40/83 (48%)

Deaths: 12/83

Serious adverse events (55 terms)

Reaction	System	Fasted Ceritinib 300mg/m2	Fasted Ceritinib 450mg/m2	Fasted Ceritinib 510mg/m2	Fasted Ceritinib 560mg/m2	Fed Ceritinib 320mg/m2	Fed Ceritinib 400mg/m2	Fed Ceritinib 500mg/m2	Fasted+Fed All Patients
Pyrexia	General disorders	—	—	—	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Device related infection	Infections and infestations	—	—	—	—	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—	—	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—	—	—	—	—	—
Influenza	Infections and infestations	—	—	—	—	—	—	—	—
Sepsis	Infections and infestations	—	—	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—
Febrile neutropenia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—
Chest pain	General disorders	—	—	—	—	—	—	—	—
Gastroenteritis	Infections and infestations	—	—	—	—	—	—	—	—
Lipase increased	Investigations	—	—	—	—	—	—	—	—
Seizure	Nervous system disorders	—	—	—	—	—	—	—	—
Suicide attempt	Psychiatric disorders	—	—	—	—	—	—	—	—
Acute kidney injury	Renal and urinary disorders	—	—	—	—	—	—	—	—
Febrile bone marrow aplasia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—
Cardiac failure	Cardiac disorders	—	—	—	—	—	—	—	—
Pericarditis	Cardiac disorders	—	—	—	—	—	—	—	—
Abdominal distension	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Ascites	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Dental caries	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Gastric haemorrhage	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Small intestinal haemorrhage	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Subileus	Gastrointestinal disorders	—	—	—	—	—	—	—	—

Other adverse events (192 terms — click to expand)

Reaction	System	Fasted Ceritinib 300mg/m2	Fasted Ceritinib 450mg/m2	Fasted Ceritinib 510mg/m2	Fasted Ceritinib 560mg/m2	Fed Ceritinib 320mg/m2	Fed Ceritinib 400mg/m2	Fed Ceritinib 500mg/m2	Fasted+Fed All Patients
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—	—	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—	—	—	—
Gamma-glutamyltransferase increased	Investigations	—	—	—	—	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—	—	—	—
Blood creatinine increased	Investigations	—	—	—	—	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Weight decreased	Investigations	—	—	—	—	—	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—
Chest pain	General disorders	—	—	—	—	—	—	—	—
Rhinitis	Infections and infestations	—	—	—	—	—	—	—	—
Blood lactate dehydrogenase increased	Investigations	—	—	—	—	—	—	—	—
Neutropenia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—
Asthenia	General disorders	—	—	—	—	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—	—	—	—	—
Blood alkaline phosphatase increased	Investigations	—	—	—	—	—	—	—	—
Lipase increased	Investigations	—	—	—	—	—	—	—	—
Leukopenia	Blood and lymphatic system disorders	—	—	—	—	—	—	—	—
Blood bilirubin increased	Investigations	—	—	—	—	—	—	—	—
Hypophosphataemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Hyponatraemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—
Dyspepsia	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Stomatitis	Gastrointestinal disorders	—	—	—	—	—	—	—	—
Amylase increased	Investigations	—	—	—	—	—	—	—	—
C-reactive protein increased	Investigations	—	—	—	—	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—

Most-reported serious reactions: Pyrexia, Abdominal pain, Device related infection, Alanine aminotransferase increased, Aspartate aminotransferase increased, Influenza, Sepsis, Anaemia.

Data from ClinicalTrials.gov NCT01742286 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Advances in Risk Classification and Treatment Strategies for Neuroblastoma.
   Pinto NR, Applebaum MA, Volchenboum SL, Matthay KK, et al · · 2015 · cited 676× · PMID 26304901 · DOI 10.1200/jco.2014.59.4648
2. Molecular targeting therapies for neuroblastoma: Progress and challenges.
   Zafar A, Wang W, Liu G, Wang X, et al · · 2021 · cited 291× · PMID 33155698 · DOI 10.1002/med.21750
3. ALK in Neuroblastoma: Biological and Therapeutic Implications.
   Trigg RM, Turner SD. · · 2018 · cited 101× · PMID 29642598 · DOI 10.3390/cancers10040113
4. New strategies in neuroblastoma: Therapeutic targeting of MYCN and ALK.
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