Phase I Study of LDK378 in Pediatric, Malignancies With a Genetic Alteration in Anaplastic Lymphoma Kinase (ALK)

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
• •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
• •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