The first phase of a study in which young patients that have diseases where an enzyme called anaplastic lymphoma kinase (ALK) is changed from it's original form are treated by increasing doses of the drug LDK378 and where all study participants are aware of what treatment the patients are receiving.

• Register: EUCTR
• Last refreshed on: 3 November 2020
• Main ID: EUCTR2012-002074-31-NL
• Date of registration: 08/05/2013
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: The first phase of a study in which young patients that have diseases where an enzyme called anaplastic lymphoma kinase (ALK) is changed from it's original form are treated by increasing doses of the drug LDK378 and where all study participants are aware of what treatment the patients are receiving.
• 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: 06/08/2013
• 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: Submission Specialist
• Affiliation: Novartis Pharma BV

• Name: Submission Specialist
• Affiliation: Novartis Pharma BV

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
Pharmaceutical Form: Capsule
INN or Proposed INN: Not established
CAS Number: 1032900-25-6
Current Sponsor code: LDK378
Other descriptive name: LDK378
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Product Code: LDK378
Pharmaceutical Form: Capsule
INN or Proposed INN: Not established
CAS Number: 1032900-25-6
Current Sponsor code: LDK378
Other descriptive name: LDK378
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Primary Outcome(s)

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

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

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)

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

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.

Secondary ID(s)

CLDK378X2103

2012-002074-31-DE

Source(s) of Monetary Support

Novartis Pharma Services AG

Ethics review

Status: Approved
Approval date: 06/08/2013
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