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)

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 6

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

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;- History of known of interstitial lung disease or interstitial pneumonitis, including
clinically significant radiation pneumonitis (i.e., affecting activities of daily living or
requiring therapeutic intervention).;-Radiotherapy to lungs * 4 weeks prior to starting the study treatment or
patients who have not recovered from radiotherapy related toxicities. For
all other anatomic sites, radiotherapy * 2 weeks prior to starting the study treatment.;- 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.;- 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

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary endpoint: Incidence rate of Dose Limiting Toxicities (DLT) during the<br /><br>first cycle of LDK378 treatment.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary endpoints:<br /><br>Endpoint 1: Adverse events and serious adverse events, changes in laboratory<br /><br>values, assessments of physical examinations, vital signs and<br /><br>electrocardiograms.<br /><br>Endpoint 2: Plasma concentration time profiles, PK parameters, including but<br /><br>not limited to AUClast, AUCtau, Cmin, Cmax, Tmax, Racc, and T1/2,acc<br /><br>Endpoint 3: Overall response rate (ORR) and duration of response (DOR),<br /><br>progression-free survival (PFS) as per RECIST 1.1 in patients with<br /><br>neuroblastoma and other solid tumors, and by International Working Group (IWG)<br /><br>criteria in patients with lymphoma. MIBG response in patients with<br /><br>neuroblastoma. Resolution of bone marrow disease in patients with<br /><br>neuroblastoma.</p><br>