Phase I/II trial of afatinib in pediatric tumours

Phase 1

• Conditions: Paediatric patients with recurrent/refractory high grade glioma (HGG), diffuse intrinsic pontine glioma (DIPG), low grade astrocytoma, neuroblastoma, ependymoma, medulloblastoma/primitive neuroectodermal tumours (PNET), rhabdomyosarcoma (RMS) and/or other solid tumours with known ErbB pathway deregulation regardless of tumour histology; MedDRA version: 20.0 Level: LLT Classification code 10029091 Term: Neoplasm of unspecified nature of endocrine glands and other parts of nervous system System Organ Class: 100000004864; MedDRA version: 20.0 Level: LLT Classification code 10029050 Term: Neoplasm of uncertain behaviour of connective and other soft tissue System Organ Class: 100000004864; MedDRA version: 21.0 Level: LLT Classification code 10028992 Term: Neoplasm CNS System Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]; MedDRA version: 20.0 Level: LLT Classification code 10029006 Term: Neoplasm of uncertain behavior of brain and spinal cord System Organ Class: 100000004864

• Registration Number: EUCTR2014-002123-10-GB
• Lead Sponsor: Boehringer Ingelheim Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-02-11
• Last Update Posted: 1 February 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 55

Inclusion Criteria

- Paediatric patients
- aged =1 year - <18 years at the time of informed consent
- who present with recurrent/refractory disease after they received at least one prior standard treatment regimen and for whom no effective conventional therapy exists
- Dose finding part: patients with a diagnosis of HGG, DIPG, low grade astrocytoma, neuroblastoma, ependymoma, medulloblastoma/PNET, RMS, and/or solid tumours with known ErbB pathway deregulation regardless of tumour histology.
- MTD expansion cohorts/Phase II part: Patients with HGG, DIPG, EM and other solid tumours than aforementioned which fulfil at least two of the below criteria:
o EGFR gene amplification (FISH): Either EGFR/Cen7 = 2.0 or =10% of cells with =15 copies or =40% of cells with = 4 copies or gene cluster in =10% of cells and/or
o HER2 gene amplification (DDISH): Her2/CEP17 = 2.0 and/or
o EGFR protein expression: H-score > 150 (membrane staining)
and/or
o HER2 protein expression: H-score > 0 (membrane staining)

Inclusion will be based on biomarker assessment prior to inclusion, as detected by central laboratory analysis of tumour biopsy material
- Patients with proven genomic, transcriptomic or proteomic ErbB alterations which are not defined in the above regardless of tumour histology
-Performance status >= 50% (Lansky for =<12ys; Karnofsky for >12ys)

Are the trial subjects under 18? yes
Number of subjects for this age range: 55
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

-relevant toxicity from previous treatment
-known pre-existing relevant cardiac , hepatic, renal, bone marrow dysfunction, ILD, keratitis

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified