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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: 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)

Brief Summary: The purpose of this study is 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.

Detailed Summary:

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.


Sponsor: Novartis Pharmaceuticals

Current Primary Outcome: Incidence rate of Dose Limiting Toxicities (DLT) [ Time Frame: up to day 21 after the patient's first dose ]

cycle = within the first 21 days of patient's first dose


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Number of patients with Adverse events [ Time Frame: 30 months ]
    Characterize the safety and tolerability of LDK378 in the pediatric patients
  • Changes in laboratory values [ Time Frame: 30 months ]
    Characterize the safety and tolerability of LDK378 in the pediatric patients
  • Assessments of physical examinations [ Time Frame: 30 months ]
    Characterize the safety and tolerability of LDK378 in the pediatric patients
  • Assessments of vital signs and electrocardiograms [ Time Frame: 30 months ]
    Characterize the safety and tolerability of LDK378 in the pediatric patients
  • Plasma concentration time profiles [ Time Frame: 30 months ]
    Characterize single and multiple-dose PK of LDK378 in pediatric patients
  • Overall response rate (ORR) [ Time Frame: 30 months ]
    Assess the anti-tumor activity of LDK378
  • Duration of response (DoR) [ Time Frame: 30 months ]
    Assess the anti-tumor activity of LDK378
  • Progression free survival (PFS) [ Time Frame: 30 months ]
    Assess the anti-tumor activity of LDK378 as per RECIST 1.1
  • Changes in disease burden in patients with lymphoma [ Time Frame: 30 months ]
    Assess the anti-tumor activity of LDK378 as per International Working Group (IWG) criteria
  • Number of patients with serious adverse events [ Time Frame: 30 months ]
    Characterize the safety and tolerability of LDK378 in the pediatric patients
  • PK parameter: AUCtau [ Time Frame: 30 months ]
    Characterize single and multiple-dose PK of LDK378 in pediatric patients
  • PK parameter: Cmin [ Time Frame: 30 months ]
    Characterize single and multiple-dose PK of LDK378 in pediatric patients
  • PK parameter: Cmax [ Time Frame: 30 months ]
    Characterize single and multiple-dose PK of LDK378 in pediatric patients
  • PK parameter: Tmax [ Time Frame: 30 months ]
    Characterize single and multiple-dose PK of LDK378 in pediatric patients
  • PK parameter: Racc [ Time Frame: 30 months ]
    Characterize single and multiple-dose PK of LDK378 in pediatric patients
  • PK parameter: t1/2 [ Time Frame: 30 months ]
    Characterize single and multiple-dose PK of LDK378 in pediatric patients
  • PK parameter: acc [ Time Frame: 30 months ]
    Characterize single and multiple-dose PK of LDK378 in pediatric patients


Original Secondary Outcome:

  • Number of patients with Adverse events [ Time Frame: 30 months ]
    Characterize the safety and tolerability of LDK378 in the pediatric patients
  • Changes in laboratory values [ Time Frame: 30 months ]
    Characterize the safety and tolerability of LDK378 in the pediatric patients
  • Assessments of physical examinations [ Time Frame: 30 months ]
    Characterize the safety and tolerability of LDK378 in the pediatric patients
  • Assessments of vital signs and electrocardiograms [ Time Frame: 30 months ]
    Characterize the safety and tolerability of LDK378 in the pediatric patients
  • Plasma concentration time profiles [ Time Frame: 30 months ]
    Characterize the safety and tolerability of LDK378 in the pediatric patients
  • Overall response rate (ORR) [ Time Frame: 30 months ]
    Assess the anti-tumor activity of LDK378
  • Duration of response (DoR) [ Time Frame: 30 months ]
    Assess the anti-tumor activity of LDK378
  • Progression free survival (PFS) [ Time Frame: 30 months ]
    Assess the anti-tumor activity of LDK378 as per RECIST 1.1
  • Changes in disease burden in patients with lymphoma [ Time Frame: 30 months ]
    Assess the anti-tumor activity of LDK378 as per International Working Group (IWG) criteria
  • Number of patients with serious adverse events [ Time Frame: 30 months ]
    Characterize the safety and tolerability of LDK378 in the pediatric patients
  • Pharmacokinetics (PK) parameter: AUClast [ Time Frame: 30 months ]
    Characterize single and multiple-dose PK of LDK378 in pediatric patients
  • PK parameter: AUCtau [ Time Frame: 30 months ]
    Characterize single and multiple-dose PK of LDK378 in pediatric patients
  • PK parameter: Cmin [ Time Frame: 30 months ]
    Characterize single and multiple-dose PK of LDK378 in pediatric patients
  • PK parameter: Cmax [ Time Frame: 30 months ]
    Characterize single and multiple-dose PK of LDK378 in pediatric patients
  • PK parameter: Tmax [ Time Frame: 30 months ]
    Characterize single and multiple-dose PK of LDK378 in pediatric patients
  • PK parameter: Racc [ Time Frame: 30 months ]
    Characterize single and multiple-dose PK of LDK378 in pediatric patients
  • PK parameter: t1/2 [ Time Frame: 30 months ]
    Characterize single and multiple-dose PK of LDK378 in pediatric patients
  • PK parameter: acc [ Time Frame: 30 months ]
    Characterize single and multiple-dose PK of LDK378 in pediatric patients


Information By: Novartis

Dates:
Date Received: November 30, 2012
Date Started: August 28, 2013
Date Completion: August 7, 2018
Last Updated: April 4, 2017
Last Verified: April 2017