Clinical Trials /

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

NCT01742286

Description:

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.

Related Conditions:
  • Cancer
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: CLDK378X2103
  • SECONDARY ID: 2012-002074-31
  • NCT ID: NCT01742286

Trial Conditions

  • Anaplastic Lymphoma Kinase (ALK)

Trial Interventions

DrugSynonymsArms
LDK378LDK378

Trial Purpose

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 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.

Trial Arms

NameTypeDescriptionInterventions
LDK378ExperimentalSingle-agent LDK378
  • LDK378

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

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

- 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

Other protocol defined inclusion and exclusion criteria may apply

Maximum Eligible Age:17 Years
Minimum Eligible Age:12 Months
Eligible Gender:Both
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence rate of Dose Limiting Toxicities (DLT)
Time Frame:up to day 21 after the patient's first dose
Safety Issue:Yes
Description:cycle = within the first 21 days of patient's first dose

Secondary Outcome Measures

Measure:Number of patients with Adverse events
Time Frame:30 months
Safety Issue:Yes
Description:Characterize the safety and tolerability of LDK378 in the pediatric patients
Measure:Changes in laboratory values
Time Frame:30 months
Safety Issue:Yes
Description:Characterize the safety and tolerability of LDK378 in the pediatric patients
Measure:Assessments of physical examinations
Time Frame:30 months
Safety Issue:Yes
Description:Characterize the safety and tolerability of LDK378 in the pediatric patients
Measure:Assessments of vital signs and electrocardiograms
Time Frame:30 months
Safety Issue:Yes
Description:Characterize the safety and tolerability of LDK378 in the pediatric patients
Measure:Plasma concentration time profiles
Time Frame:30 months
Safety Issue:No
Description:Characterize single and multiple-dose PK of LDK378 in pediatric patients
Measure:Overall response rate (ORR)
Time Frame:30 months
Safety Issue:No
Description:Assess the anti-tumor activity of LDK378
Measure:Duration of response (DoR)
Time Frame:30 months
Safety Issue:No
Description:Assess the anti-tumor activity of LDK378
Measure:Progression free survival (PFS)
Time Frame:30 months
Safety Issue:No
Description:Assess the anti-tumor activity of LDK378 as per RECIST 1.1
Measure:Changes in disease burden in patients with lymphoma
Time Frame:30 months
Safety Issue:No
Description:Assess the anti-tumor activity of LDK378 as per International Working Group (IWG) criteria
Measure:Number of patients with serious adverse events
Time Frame:30 months
Safety Issue:Yes
Description:Characterize the safety and tolerability of LDK378 in the pediatric patients
Measure:PK parameter: AUCtau
Time Frame:30 months
Safety Issue:No
Description:Characterize single and multiple-dose PK of LDK378 in pediatric patients
Measure:PK parameter: Cmin
Time Frame:30 months
Safety Issue:No
Description:Characterize single and multiple-dose PK of LDK378 in pediatric patients
Measure:PK parameter: Cmax
Time Frame:30 months
Safety Issue:No
Description:Characterize single and multiple-dose PK of LDK378 in pediatric patients
Measure:PK parameter: Tmax
Time Frame:30 months
Safety Issue:No
Description:Characterize single and multiple-dose PK of LDK378 in pediatric patients
Measure:PK parameter: Racc
Time Frame:30 months
Safety Issue:No
Description:Characterize single and multiple-dose PK of LDK378 in pediatric patients
Measure:PK parameter: t1/2
Time Frame:30 months
Safety Issue:No
Description:Characterize single and multiple-dose PK of LDK378 in pediatric patients
Measure:PK parameter: acc
Time Frame:30 months
Safety Issue:No
Description:Characterize single and multiple-dose PK of LDK378 in pediatric patients

Trial Keywords

  • pediatric, anaplastic lymphoma kinase, ALK-activated tumors, neuroblastoma, rhabdomyosarcoma, anaplastic large-cell lymphoma, inflammatory myofibroblastic tumor