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) - Phase I study of LDK378 in pediatric malignancies with a genetic alteration in ALK

• Register: EUCTR
• Last refreshed on: 10 December 2019
• Main ID: EUCTR2012-002074-31-DE
• Date of registration: 26/04/2013
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public 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) - Phase I study of LDK378 in pediatric malignancies with a genetic alteration in 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) - Phase I study of LDK378 in pediatric malignancies with a genetic alteration in ALK
• Date of first enrolment: 13/11/2013
• Target sample size: 105
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-002074-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Canada, France, Germany, Italy, Korea, Republic of, Netherlands, Spain, United Kingdom, United States

Contacts

• Name: Medizinischer Infoservice (MCC)
• Affiliation: Novartis Pharma GmbH

• Name: Medizinischer Infoservice (MCC)
• Affiliation: Novartis Pharma GmbH

Key inclusion & exclusion criteria

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

Other protocol-defined inclusion criteria may apply
Are the trial subjects under 18? yes
Number of subjects for this age range: 80
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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
- Clinically significant, uncontrolled heart disease
- Inadequate end organ function as defined by specified laboratory values
- 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
- Medications with a known risk of prolongation of QT interval
- Patient has a history of pancreatitis or history of increased amylase or lipase that was due to pancreatic disease
Other protocol-defined exclusion criteria may apply


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

malignancies characterized by genetic abnormalities in anaplastic lymphoma kinase (ALK)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Code: LDK378 50mg
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Ceritinib
Other descriptive name: LDK378
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Product Code: LDK378 150mg (pink opaque)
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Ceritinib
Other descriptive name: LDK378
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Product Code: LDK378 150mg (blue/white)
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Ceritinib
Other descriptive name: LDK378
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Product Code: LDK378 150mg (blue opaque/white opaque)
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Ceritinib
Other descriptive name: LDK378
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Primary Outcome(s)

Secondary Objective: 1 -Characterize the safety and tolerability of LDK378 in the pediatric patients in the fasted and fed state
2- Characterize single and multiple-dose PK of LDK378 in pediatric patients in the fasted and fed state
3- Assess the anti-tumor activity of LDK378 in the fasted and fed state

Primary end point(s): Incidence rate of Dose Limiting Toxicities (DLT)

Main Objective: Estimate the MTD and/or RDE of LDK378 as a single agent when administered orally to pediatric patients with ALK-activated tumors in the fasted and fed state

Timepoint(s) of evaluation of this end point: up to day 21 after the patient's first dose

Secondary Outcome(s)

Secondary end point(s): 1- Number of patients with Adverse events and serious adverse events; Changes in laboratory values ; Assessments of physical examinations; Assessments of vital signs and electrocardiograms; Plasma concentration time profiles

2- PK parameters, including AUClast, AUCtau, Cmin, Cmax, Tmax, Racc T1/2 and acc

3- Overall response rate (ORR) and duration of response (DOR), progression-free survival (PFS) as per RECIST 1.1; Changes in disease burden in patients with lymphoma.

Timepoint(s) of evaluation of this end point: 1- 30 months
2- 30 months
3- 30 months

Secondary ID(s)

CLDK378X2103

Source(s) of Monetary Support

Novartis Pharma Services AG

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 11/11/2019
• Date Completed: 26/04/2019
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-002074-31/results