Phase I study of LDK378 in pediatric malignancies with a genetic alteration in ALK

Phase 1

Conditions: malignancies characterized by genetic abnormalities in anaplastic lymphoma kinase (ALK)
MedDRA version: 14.1Level: LLTClassification code 10029261Term: Neuroblastoma NOSSystem Organ Class: 100000004864
MedDRA version: 14.1Level: LLTClassification code 10002228Term: Anaplastic large cell lymphoma T- and null-cell types NOSSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2012-002074-31-IT

Lead Sponsor: ovartis Pharma S.p.A.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 80

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 = 17years
- The tumor must carry a genetic alteration of ALK
- Patients must have evaluable or measurable disease

Other protocol-defined inclusion criteria may apply
Are the trial subjects under 18? yes
Number of subjects for this age range: 80
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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.
Other protocol-defined exclusion criteria may apply

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Estimate the MTD and/or RDE of LDK378 as a single agent when administered orally to pediatric patients with ALK-activated tumors ;Secondary Objective: 1 -Characterize the safety and tolerability of LDK378 in the pediatric patients<br>2- Characterize single and multiple-dose PK of LDK378 in pediatric patients<br>3- Assess the anti-tumor activity of LDK378;Primary end point(s): Incidence rate of Dose Limiting Toxicities (DLT);Timepoint(s) of evaluation of this end point: up to day 21 after the patient's first dose

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1- Number of patients with Adverse events and serious adverse events; Changes in laboratory values ; Assessments of physical examinations; Assessments of vital signs and electrocardiograms; Plasma concentration time profiles<br><br>2- PK parameters, including AUClast, AUCtau, Cmin, Cmax, Tmax, Racc T1/2 and acc<br><br>3- Overall response rate (ORR) and duration of response (DOR), progression-free survival (PFS) as per RECIST 1.1; Changes in disease burden in patients with lymphoma.;Timepoint(s) of evaluation of this end point: 1- 30 months<br>2- 30 months<br>3- 30 months<br>

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