Phase I Study of LDK378 in Pediatric, Malignancies With a Genetic Alteration in Anaplastic Lymphoma Kinase (ALK)
Conditions
Anaplastic Lymphoma Kinase (ALK)
Conditions: official terms
Lymphoma
Conditions: Keywords
pediatric, anaplastic lymphoma kinase, ALK-activated tumors, neuroblastoma, rhabdomyosarcoma, anaplastic large-cell lymphoma, inflammatory myofibroblastic tumor
Study Type
Interventional
Study Phase
Phase 1
Study Design
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: LDK378
Type: Drug
Overall Status
Recruiting
Summary
The purpose of this study is to estimate the maximum tolerated dose 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.
Detailed Description
LDK378 is a novel inhibitor of ALK that is active in a broad range of ALK-activated tumor models, including models driven by mutated versions of ALK known to be resistant to crizotinib, and by ALK gene amplification.

The primary purpose of this study is to determine the maximum tolerated dose and/or recommended dose for expansion in pediatric patients, and to delineate a clinical dose to be used in any future pediatric studies, with and without food. This study will also assess the safety, tolerability, PK and preliminary evidence of antitumor activity of LDK378 in pediatric patients with neuroblastoma, and other ALK-activated tumors.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: 17 Years
Minimum Age: 12 Months
Gender: Both
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

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

- 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
Locations
University of California at Los Angeles UCLA LeConte Location
Los Angeles, California, United States
Status: Withdrawn
Children's Healthcare of Atlanta Dept of Oncology
Atlanta, Georgia, United States
Status: Recruiting
Contact: Katherine Garrett - 404-785-3535 - Katherine.garrett@choa.org
Dana Farber Cancer Institute Dept of Onc
Boston, Massachusetts, United States
Status: Recruiting
Contact: Mei Yang - 617-582-7169 - Mei_yang@dfci.harvard.edu
Memorial Sloan Kettering Cancer Center SC - 7
New York, New York, United States
Status: Recruiting
Contact: Virginia Cabezon - 646-888-5716 - cabezonv@mskcc.org
Cincinnati Children's Hospital Medical Center Dept of Oncology
Cincinnati, Ohio, United States
Status: Recruiting
Contact: Brian Poole - 513-636-9419 - brian.poole@cchmc.org
St. Jude's Children's Research Hospital Dept of Oncology
Memphis, Tennessee, United States
Status: Recruiting
Contact: Rose Anne Speights - +1 901 595 4616 - roseanne.speights@stjude.org
Texas Children's Hospital Dept of Oncology
Houston, Texas, United States
Status: Recruiting
Contact: Meg Tucker-Hall - 832-824-4570 - mxtucker@txch.org
Novartis Investigative Site
Randwick, New South Wales, Australia
Status: Recruiting
Novartis Investigative Site
Parkville, Victoria, Australia
Status: Recruiting
Novartis Investigative Site
Toronto, Ontario, Canada
Status: Recruiting
Novartis Investigative Site
Paris, France
Status: Recruiting
Novartis Investigative Site
Villejuif Cedex, France
Status: Recruiting
Novartis Investigative Site
Essen, Germany
Status: Recruiting
Novartis Investigative Site
Köln, Germany
Status: Recruiting
Novartis Investigative Site
Milano, MI, Italy
Status: Recruiting
Novartis Investigative Site
Seoul, Korea, Korea, Republic of
Status: Recruiting
Novartis Investigative Site
Seoul, Korea, Korea, Republic of
Status: Withdrawn
Novartis Investigative Site
Amsterdam, Netherlands
Status: Recruiting
Novartis Investigative Site
Rotterdam, Netherlands
Status: Recruiting
Novartis Investigative Site
Barcelona, Catalunya, Spain
Status: Recruiting
Novartis Investigative Site
Valencia, Comunidad Valenciana, Spain
Status: Recruiting
Novartis Investigative Site
Madrid, Spain
Status: Recruiting
Novartis Investigative Site
Sutton, Surrey, United Kingdom
Status: Recruiting
Novartis Investigative Site
Birmingham, United Kingdom
Status: Recruiting
Start Date
February 2013
Completion Date
February 2017
Sponsors
Novartis Pharmaceuticals
Source
Novartis
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page