ALK-activated TumorsPhase 1NCT01742286
Phase I Study of LDK378 in Pediatric, Malignancies With a Genetic Alteration in Anaplastic Lymphoma Kinase (ALK)
A Phase 1 study testing Ceritinib in people with ALK-activated Tumors, run by Novartis Pharmaceuticals at 23 sites in 10 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 12 months to 17 years
- Conditions the study is for
- ALK-activated Tumors
- What is being tested?
- Ceritinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 83 participants
- Where
- 23 sitesin 10 countries
- Study dates
- 28 Aug 2013to 26 Apr 2019
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 months to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
23 sites in 10 countries.
23 sites in 10 countries
United States5 sites
Dana Farber Cancer Institute Dept of Onc
Boston, Massachusetts, 02215
Cincinnati Children s Hospital Medical Center Dept of Oncology
Cincinnati, Ohio, 45229-3039
Texas Children's Hospital Dept of Oncology
Houston, Texas, 77030
St Jude s Childrens Research Hospital Dept of Oncology
Memphis, Tennessee, 38105-2794
Memorial Sloan Kettering SC - 7
New York, New York, 10017
Germany3 sites
Novartis Investigative Site
Berlin, 13353
Novartis Investigative Site
Cologne, North Rhine-Westphalia, 50937
Novartis Investigative Site
Essen, 45147
Netherlands3 sites
Novartis Investigative Site
Amsterdam, 1105 AZ
Novartis Investigative Site
Rotterdam, 3015 CN
Novartis Investigative Site
Utrecht, CS, 3584
Spain3 sites
Novartis Investigative Site
Barcelona, Catalonia, 08035
Novartis Investigative Site
Madrid, 28009
Novartis Investigative Site
Valencia, Valencia, 46026
Australia2 sites
Novartis Investigative Site
Parkville, Victoria, 3052
Novartis Investigative Site
Randwick, New South Wales, 2130
France2 sites
Novartis Investigative Site
Paris, 75231
Novartis Investigative Site
Villejuif, 94805
United Kingdom2 sites
Novartis Investigative Site
Sutton, Surrey, SM2 5PT
Novartis Investigative Site
West Midlands, Birmingham, B4 6NH
About this study
Official 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)
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.
Read the detailed description
LDK378 is a novel inhibitor of ALK that is active in a broad range of ALK-activated tumor models, including models driven by mutated versions of ALK known to be resistant to crizotinib, and by ALK gene amplification.
The primary purpose of this study was to determine the maximum tolerated dose and/or recommended dose for expansion in pediatric patients, and to delineate a clinical dose to be used in any future pediatric studies, with and without food. This study also assessed the safety, tolerability, PK and preliminary evidence of antitumor activity of LDK378 in pediatric patients with neuroblastoma, and other ALK-activated tumors.
Fasted cohort: each daily dose of LDK378 (including days which involved PK blood sampling) was taken at least 2 hours after last meal \& subjects did not eat until 1 hour after LDK378 was taken. Each daily dose of LDK378 was taken with 1-2 tablespoons (15-30 mL) of an appropriate food (such as applesauce or non-fat yogurt) \& a glass of water
Fed cohort: each daily dose of LDK378 (including days which involved PK blood sampling) was taken with, or within 30 minutes after finishing a low-fat light snack containing 100-300 calories \& 1.5-2 grams of fat.
- Conditions
- ALK-activated Tumors
- Being tested
- Ceritinib
- Keywords
- LDK378, Ceritinib, pediatric, malignancies, anaplastic lymphoma kinase, ALK, ALK-activated tumors, neuroblastoma, rhabdomyosarcoma, anaplastic large-cell lymphoma, inflammatory myofibroblastic tumor
- Medical subject headings
- Neoplasms, Neuroblastoma, Rhabdomyosarcoma, Lymphoma, Large-Cell, Anaplastic, Granuloma, Plasma Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CeritinibDrug
Also called LDK378
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.
| Study group | Role | What they receive |
|---|---|---|
| LDK378 | Experimental | All participants were administered a single-agent LDK378 (Ceritinib) orally, once daily, continuously in fasted or fed conditions. Receives: Drug: Ceritinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence Rate of Dose Limiting Toxicities (DLTs) Occurring During First Cycle of Treatment
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.
Measured: up to day 21 after the patient's first dose; cycle = within the first 21 days of patient's first dose
Secondary outcomes (15)
Summary of Best Overall Response by Overall Response Rate (ORR) Per Investigator Assessment
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 lesion, taking as reference the baseline sum diameters. Per IWG criteria (for patients with lymphoma): CR: normalization of all index nodal lesions or complete disappearance of all index extranodal lesions. PR: at least 50% decrease from baseline in the sum of diameters of all index lesions.
Measured: 30 months
Duration of Response (DoR) Per Investigator Assessment
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 the sum of diameter of all target lesion, taking as reference the baseline sum diameters. Per IWG criteria (for patients with lymphoma): CR: normalization of all index nodal lesions or complete disappearance of all index extranodal lesions. PR: at least 50% decrease from baseline in the sum of diameters of all index lesions.
Measured: 30 months
Progression Free Survival (PFS) Based on Investigator Assessment
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 the sum of diameter of all target lesion, taking as reference the baseline sum diameters. Per IWG criteria (for patients with lymphoma): CR: normalization of all index nodal lesions or complete disappearance of all index extranodal lesions. PR: at least 50% decrease from baseline in the sum of diameters of all index lesions.
Measured: 30 months
Plasma Concentration Time Profiles by Treatment Group in Escalation Phase
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.
Measured: 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
Plasma Concentration Time Profiles by Treatment Group in Expansion Phase
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.
Measured: 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
Pharmacokinetics (PK) Parameters: AUC0 - 24h & AUClast in Cycle 1 Day 1 - Dose Escalation Phase (Single 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
Measured: 0hr pre-dose, 2, 4, 6 & 24hrs post-dose
Pharmacokinetics (PK) Parameters: AUC0 - 24h & AUClast in Cycle 2 Day 1 - Dose Escalation Phase (Single 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
Measured: 0hr pre-dose, 2, 4, 6 & 24hrs post-dose
Pharmacokinetics (PK) Parameters: AUC0 - 24h & AUClast in Cycle 2 Day 1 - Dose Expansion Phase (Multiple 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
Measured: 0hr pre-dose, 2, 4, 6 & 24hrs post-dose
PK Parameter: Cmax in Cycle 1 Day 1 - Dose Escalation Phase (Single Dose)
Characterize single and multiple-dose PK of LDK378 in pediatric patients. Cmax: Maximum (peak) concentration of drug
Measured: 0hr pre-dose, 2, 4, 6 & 24hrs post-dose
PK Parameter: Cmax in Cycle 2 Day 1 - Dose Escalation Phase (Single Dose)
Characterize single and multiple-dose PK of LDK378 in pediatric patients. Cmax: Maximum (peak) concentration of drug.
Measured: 0hr pre-dose, 2, 4, 6 & 24hrs post-dose
PK Parameter: Cmax in Cycle 2 Day 1 - Dose Expansion Phase (Multiple 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
Measured: 0hr pre-dose, 2, 4, 6 & 24hrs post-dose
PK Parameter: Tmax in Cycle 1 Day 1 - Dose Escalation Phase (Single Dose)
Characterize single and multiple-dose PK of LDK378 in pediatric patients. Tmax: The time to reach maximum plasma concentration
Measured: 0hr pre-dose, 2, 4, 6 & 24hrs post-dose
PK Parameter: Tmax in Cycle 2 Day 1 - Dose Escalation Phase (Single Dose)
Characterize single and multiple-dose PK of LDK378 in pediatric patients. Tmax: The time to reach maximum plasma concentration
Measured: 0hr pre-dose, 2, 4, 6 & 24hrs post-dose
PK Parameter: Tmax in Cycle 2 Day 1 - Dose Expansion Phase (Multiple 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.
Characterize single and multiple-dose PK of LDK378 in pediatric patients. Tmax: The time to reach maximum plasma concentration
Measured: 0hr pre-dose, 2, 4, 6 & 24hrs post-dose
PK Parameter: Racc in Dose Escalation Phase Cycle 2 Day 1
Characterize single and multiple-dose PK of LDK378 in pediatric patients. Racc: Accumulation ratio
Measured: 0hr pre-dose, 2, 4, 6 & 24hrs post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2012 (estimated)
- Study start28 Aug 2013
- Primary completion26 Apr 2019
- Study completion26 Apr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for ALK-activated TumorsStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 83 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01742286
- Sponsor's protocol ID
- CLDK378X2103
- Other IDs
- 2012-002074-31
- Status last verified
- May 2020
- First submitted
- 30 Nov 2012
- Last updated
- 9 Jun 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 34780709Brivio 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.
PubMed 30697903
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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)
- ClinicalTrials.gov ID
- NCT01742286
- Acronym / sponsor ID
- CLDK378X2103
- Conditions
- ALK-activated Tumors
- Keywords
- LDK378, Ceritinib, pediatric, malignancies, anaplastic lymphoma kinase, ALK, ALK-activated tumors, neuroblastoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 83 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 28 Aug 2013 (actual)
- Primary completion
- 26 Apr 2019 (actual)
- Study completion
- 26 Apr 2019 (actual)
- First posted
- 5 Dec 2012 (estimated)
- Results
- Posted 9 Jun 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
LDK378 is a novel inhibitor of ALK that is active in a broad range of ALK-activated tumor models, including models driven by mutated versions of ALK known to be resistant to crizotinib, and by ALK gene amplification.
The primary purpose of this study was to determine the maximum tolerated dose and/or recommended dose for expansion in pediatric patients, and to delineate a clinical dose to be used in any future pediatric studies, with and without food. This study also assessed the safety, tolerability, PK and preliminary evidence of antitumor activity of LDK378 in pediatric patients with neuroblastoma, and other ALK-activated tumors.
Fasted cohort: each daily dose of LDK378 (including days which involved PK blood sampling) was taken at least 2 hours after last meal \& subjects did not eat until 1 hour after LDK378 was taken. Each daily dose of LDK378 was taken with 1-2 tablespoons (15-30 mL) of an appropriate food (such as applesauce or non-fat yogurt) \& a glass of water
Fed cohort: each daily dose of LDK378 (including days which involved PK blood sampling) was taken with, or within 30 minutes after finishing a low-fat light snack containing 100-300 calories \& 1.5-2 grams of fat.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| LDK378 | Experimental | Drug: CeritinibAll participants were administered a single-agent LDK378 (Ceritinib) orally, once daily, continuously in fasted or fed conditions. |
Who may qualify
- Ages
- 12 months to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CeritinibAlso: LDK378LDK378 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. | Drug | LDK378 |
Primary outcome
Incidence Rate of Dose Limiting Toxicities (DLTs) Occurring During First Cycle of Treatment
Time frame: 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.
15 secondary outcomes
Summary of Best Overall Response by Overall Response Rate (ORR) Per Investigator Assessment
Time frame: 30 months
Duration of Response (DoR) Per Investigator Assessment
Time frame: 30 months
Progression Free Survival (PFS) Based on Investigator Assessment
Time frame: 30 months
Plasma Concentration Time Profiles by Treatment Group in Escalation Phase
Time frame: 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
Plasma Concentration Time Profiles by Treatment Group in Expansion Phase
Time frame: 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
Pharmacokinetics (PK) Parameters: AUC0 - 24h & AUClast in Cycle 1 Day 1 - Dose Escalation Phase (Single Dose)
Time frame: 0hr pre-dose, 2, 4, 6 & 24hrs post-dose
Pharmacokinetics (PK) Parameters: AUC0 - 24h & AUClast in Cycle 2 Day 1 - Dose Escalation Phase (Single Dose)
Time frame: 0hr pre-dose, 2, 4, 6 & 24hrs post-dose
Pharmacokinetics (PK) Parameters: AUC0 - 24h & AUClast in Cycle 2 Day 1 - Dose Expansion Phase (Multiple Dose)
Time frame: 0hr pre-dose, 2, 4, 6 & 24hrs post-dose
PK Parameter: Cmax in Cycle 1 Day 1 - Dose Escalation Phase (Single Dose)
Time frame: 0hr pre-dose, 2, 4, 6 & 24hrs post-dose
PK Parameter: Cmax in Cycle 2 Day 1 - Dose Escalation Phase (Single Dose)
Time frame: 0hr pre-dose, 2, 4, 6 & 24hrs post-dose
PK Parameter: Cmax in Cycle 2 Day 1 - Dose Expansion Phase (Multiple Dose)
Time frame: 0hr pre-dose, 2, 4, 6 & 24hrs post-dose
PK Parameter: Tmax in Cycle 1 Day 1 - Dose Escalation Phase (Single Dose)
Time frame: 0hr pre-dose, 2, 4, 6 & 24hrs post-dose
PK Parameter: Tmax in Cycle 2 Day 1 - Dose Escalation Phase (Single Dose)
Time frame: 0hr pre-dose, 2, 4, 6 & 24hrs post-dose
PK Parameter: Tmax in Cycle 2 Day 1 - Dose Expansion Phase (Multiple Dose)
Time frame: 0hr pre-dose, 2, 4, 6 & 24hrs post-dose
PK Parameter: Racc in Dose Escalation Phase Cycle 2 Day 1
Time frame: 0hr pre-dose, 2, 4, 6 & 24hrs post-dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34780709Fischer 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.
- Derived from this study: PubMed 30697903Brivio 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
23 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ceritinib in people with ALK-activated Tumors, run by Novartis Pharmaceuticals at 23 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in United States, Germany, Netherlands, Spain, Australia and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence Rate of Dose Limiting Toxicities (DLTs) Occurring During First Cycle of Treatment (time frame: up to day 21 after the patient's first dose; cycle = within the first 21 days of patient's first dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01742286, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2020.