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

• Status: Completed
• Trial end date: 2019-04-26
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Novartis Pharmaceuticals
• Treatments: Ceritinib

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