Phase I Study of LDK378 in Pediatric, Malignancies With a Genetic Alteration in Anaplastic Lymphoma Kinase (ALK)
Condition: ALK-activated Tumors
MeSH terms: Lymphoma; Neoplasms
Intervention: Ceritinib
Intervention description: LDK378 is a capsule taken by mouth, contents can be mixed with food for pediatric patients or mixed with water and given via nasogastric/gastric (NG/G) tube. For patients in fasted group: 1-2 tablespoons (15-30 mL) of an appropriate food such as apple sauce or non-fat yogurt and a glass of water were allowed.
For patients in the fed cohort: LDK378 was taken with, or within 30 minutes after finishing a low-fat light snack containing 100-300 calories and 1.5-2 grams of fat.
Intervention MeSH terms: Ceritinib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 83.0
Sex: All
Minimum age: 12 Months
Maximum age: 17 Years
Healthy volunteers: No
Keywords: LDK378; Ceritinib; pediatric; malignancies; anaplastic lymphoma kinase; ALK; ALK-activated tumors; neuroblastoma; rhabdomyosarcoma; anaplastic large-cell lymphoma; inflammatory myofibroblastic tumor

Summary:

      The purpose of this study was to estimate the maximum tolerated dose and/or recommended dose
      for expansion of LDK378 as a single agent, assess safety, tolerability and anti-tumor
      activity and characterize single and multiple-dose pharmacokinetics when administered orally
      to pediatric patients with ALK-activated tumors, with and without food.
    

Eligibility 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.

          -  Karnofsky performance status score ≥ 60% for patients > 12 years of age; Lansky score
             ≥ 50% for patients ≤ 12 years of age.

        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