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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01742286
First received: November 30, 2012
Last updated: May 27, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Anaplastic Lymphoma Kinase (ALK)
Drug: LDK378
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Incidence rate of Dose Limiting Toxicities (DLT) [ Time Frame: up to day 21 after the patient's first dose ] [ Designated as safety issue: Yes ]
    cycle = within the first 21 days of patient's first dose


Secondary Outcome Measures:
  • Number of patients with Adverse events [ Time Frame: 30 months ] [ Designated as safety issue: Yes ]
    Characterize the safety and tolerability of LDK378 in the pediatric patients

  • Changes in laboratory values [ Time Frame: 30 months ] [ Designated as safety issue: Yes ]
    Characterize the safety and tolerability of LDK378 in the pediatric patients

  • Assessments of physical examinations [ Time Frame: 30 months ] [ Designated as safety issue: Yes ]
    Characterize the safety and tolerability of LDK378 in the pediatric patients

  • Assessments of vital signs and electrocardiograms [ Time Frame: 30 months ] [ Designated as safety issue: Yes ]
    Characterize the safety and tolerability of LDK378 in the pediatric patients

  • Plasma concentration time profiles [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Characterize the safety and tolerability of LDK378 in the pediatric patients

  • Overall response rate (ORR) [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Assess the anti-tumor activity of LDK378

  • Duration of response (DoR) [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Assess the anti-tumor activity of LDK378

  • Progression free survival (PFS) [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Assess the anti-tumor activity of LDK378 as per RECIST 1.1

  • Changes in disease burden in patients with lymphoma [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    Characterize the safety and tolerability of LDK378 in the pediatric patients

  • Pharmacokinetics (PK) parameter: AUClast [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Characterize single and multiple-dose PK of LDK378 in pediatric patients

  • PK parameter: AUCtau [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Characterize single and multiple-dose PK of LDK378 in pediatric patients

  • PK parameter: Cmin [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Characterize single and multiple-dose PK of LDK378 in pediatric patients

  • PK parameter: Cmax [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Characterize single and multiple-dose PK of LDK378 in pediatric patients

  • PK parameter: Tmax [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Characterize single and multiple-dose PK of LDK378 in pediatric patients

  • PK parameter: Racc [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Characterize single and multiple-dose PK of LDK378 in pediatric patients

  • PK parameter: t1/2 [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Characterize single and multiple-dose PK of LDK378 in pediatric patients

  • PK parameter: acc [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    Characterize single and multiple-dose PK of LDK378 in pediatric patients


Estimated Enrollment: 80
Study Start Date: August 2013
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LDK378
Single-agent LDK378
Drug: LDK378
LDK378 is a capsule taken by mouth, contents can be mixed with food for pediatric patients or mixed with water and given via NG/G tube

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. 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.

  Eligibility

Ages Eligible for Study:   12 Months to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 ≤ 17 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01742286

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals

  Show 23 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01742286     History of Changes
Other Study ID Numbers: CLDK378X2103, 2012-002074-31
Study First Received: November 30, 2012
Last Updated: May 27, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
pediatric, anaplastic lymphoma kinase, ALK-activated tumors, neuroblastoma, rhabdomyosarcoma, anaplastic large-cell lymphoma, inflammatory myofibroblastic tumor

Additional relevant MeSH terms:
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on July 20, 2014