E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
malignancies characterized by genetic abnormalities in anaplastic lymphoma kinase (ALK) |
|
E.1.1.1 | Medical condition in easily understood language |
malignancies with genetic abnormalities in anaplastic lymphoma kinase (ALK) |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10029261 |
E.1.2 | Term | Neuroblastoma NOS |
E.1.2 | System Organ Class | 100000004864 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10002228 |
E.1.2 | Term | Anaplastic large cell lymphoma T- and null-cell types NOS |
E.1.2 | System Organ Class | 100000004864 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Estimate the MTD and/or RDE of LDK378 as a single agent when administered orally to pediatric patients with ALK-activated tumors |
|
E.2.2 | Secondary objectives of the trial |
1 -Characterize the safety and tolerability of LDK378 in the pediatric patients
2- Characterize single and multiple-dose PK of LDK378 in pediatric patients
3- Assess the anti-tumor activity of LDK378 |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 |
|
E.4 | Principal 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 |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Incidence rate of Dose Limiting Toxicities (DLT) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
up to day 21 after the patient's first dose |
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E.5.2 | 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
2- PK parameters, including AUClast, AUCtau, Cmin, Cmax, Tmax, Racc T1/2 and acc
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. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1- 30 months
2- 30 months
3- 30 months
|
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Estimate the MTD and/or RDE of LDK378 |
|
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
France |
Germany |
Italy |
Netherlands |
United Kingdom |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |