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.
- Conditions
- malignancies characterized by genetic abnormalities in anaplastic lymphoma kinase (ALK)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2012-002074-31-NL
- Lead Sponsor
- ovartis Pharma Services AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 83
- 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
- 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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;Secondary Objective: 1 -Characterize the safety and tolerability of LDK378 in the pediatric patients in the fasted and fed state<br>2- Characterize single and multiple-dose PK of LDK378 in pediatric patients in the fasted and fed state<br>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);Timepoint(s) of evaluation of this end point: up to day 21 after the patient's first dose
- Secondary Outcome Measures
Name Time Method 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<br><br>2- PK parameters, including AUClast, AUCtau, Cmin, Cmax, Tmax, Racc T1/2 and acc<br><br>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<br>2- 30 months<br>3- 30 months<br>