Clinical trial NCT02372006: Trial of Afatinib in Pediatric Tumours
Official title: Phase I/II Open Label, Dose Escalation Trial to Determine the MTD, Safety, PK and Efficacy of Afatinib Monotherapy in Children Aged ≥1 Year to <18 Years With Recurrent/Refractory Neuroectodermal Tumours, Rhabdomyosarcoma and/or Other Solid Tumours With Known ErbB Pathway Deregulation Regardless of Tumour Histology
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Neuroectodermal Tumors
Rhabdomyosarcoma
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2015-02-26
Enrollment: 56
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Open-label, dose escalation, monotherapy, basket trial with biomarker specific MTD expansion cohort/Phase II part.

The trial will consist of 2 parts:

1. Dose finding part to determine the MTD
2. Biomarker specific MTD expansion cohort/Phase II part to assess clinical anti-tumour activity in included tumour types


Eligibility criteria: Inclusion criteria:

* Paediatric patients aged 1 year to \<18 years at the time of informed consent
* diagnosis of HGG, DIPG, low grade astrocytoma, medulloblastoma/PNET, ependymoma, neuroblastoma, RMS and tumours with ErbB deregulation
* recurrent/refractory disease after they received at least one prior standard treatment regimen
* no effective conventional therapy exists
* Performance status \>= 50% (Lansky for =\<12ys; Karnofsky for \>12ys)
* Further inclusion criteria apply

Exclusion criteria:

* relevant toxicity from previous treatment
* known pre-existing relevant cardiac , hepatic, renal, bone marrow dysfunction, ILD, keratitis
* Further exclusion criteria apply

Primary outcomes:
measure: Number of Participants With Objective Response - Maximum Tolerated Dose Expansion (MTD) Cohort
timeFrame: Assessed every 8 weeks until progression of disease, up to 336 days.
measure: Area Under the Curve Over Dosing Interval τ at Steady State (AUCτ,ss) - Dose Finding Part
timeFrame: Pre-dose before afatinib administration then 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 8 h and 24 h after administration at steady state on Day 8.
measure: Maximum Measured Concentration of the Analyte in Plasma at Steady State (Cmax,ss) - Dose Finding Part
timeFrame: Pre-dose before afatinib administration then 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 8 h and 24 h after administration at steady state on Day 8.
measure: Number of Participants With Dose Limiting Toxicity Adverse Events - Dose Finding Part
timeFrame: During the first course (28 days) of treatment.
Secondary outcomes:
measure: Number of Participants With Objective Response - Dose Finding Part
timeFrame: Assessed every 8 weeks until progression of disease, up to 336 days.
measure: Progression Free Survival - Maximum Tolerated Dose (MTD) Expansion Cohort
timeFrame: From the first treatment until date of first progression or death, up to 336 days.
measure: Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to 24 Hours (AUC0-24) - Dose Finding Part
timeFrame: Pre-dose before afatinib administration then 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 8 h and 24 h after administration on Day 1.
measure: Maximum Measured Concentration (Cmax) - Dose Finding Part/Maximum Tolerated Dose (MTD) Expansion Cohort
timeFrame: Pre-dose before afatinib administration then 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 8 h and 24 h after administration on Day 1.
measure: Time From (Last) Dosing to the Maximum Measured Concentration (Tmax) - Dose Finding Part/Maximum Tolerated Dose (MTD) Expansion Cohort
timeFrame: Pre-dose before afatinib administration then 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 8 h and 24 h after administration on Day 1.
measure: Time From (Last) Dosing to the Maximum Measured Concentration at Steady State (Tmax,ss) - Dose Finding Part/Maximum Tolerated Dose (MTD) Expansion Cohort
timeFrame: Pre-dose before afatinib administration then 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 8 h and 24 h after administration at steady state on Day 8.
measure: Accumulation (or Effective) Half-life - Dose Finding Part/Maximum Tolerated Dose (MTD) Expansion Cohort
timeFrame: Pre-dose before afatinib administration then 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 8 h and 24 h after administration at steady state on Day 8.
measure: Duration of Objective Response - Maximum Tolerated Dose (MTD) Expansion Cohort
timeFrame: From first documented response until the earliest of disease progression or death, up to 336 days.
measure: Area Under the Curve Over Dosing Interval τ at Steady State (AUCτ,ss) - Maximum Tolerated Dose (MTD) Expansion Cohort
timeFrame: Pre-dose before afatinib administration then 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 8 h and 24 h after administration at steady state on Day 8.
measure: Maximum Measured Concentration of the Analyte in Plasma at Steady State (Cmax,ss) - Maximum Tolerated Dose (MTD) Expansion Cohort
timeFrame: Pre-dose before afatinib administration then 1 hour (h), 2 h, 3 h, 4 h, 5 h, 6 h, 8 h and 24 h after administration at steady state on Day 8.
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Randwick
country: Australia
facility: Sydney Childrens Hospital
state: New South Wales
city: Vienna
country: Austria
facility: AKH - Medical University of Vienna
city: Wien
country: Austria
facility: St. Anna Children-Hospital, Children's Cancer Research, Wien
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: København Ø
country: Denmark
facility: Rigshospitalet, København, Børneonkologisk Afsnit 5002
city: Toulouse
country: Faroe Islands
facility: HOP Toulouse, Pédiat, Toulouse
city: Bordeaux
country: France
facility: HOP Pellegrin
city: Lille
country: France
facility: CTR Oscar Lambret
city: Lyon
country: France
facility: CTR Leon Berard
city: Paris
country: France
facility: INS Curie
city: Villejuif
country: France
facility: INS Gustave Roussy
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Essen
country: Germany
facility: Universitätsklinikum Essen AöR
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Genova
country: Italy
facility: Istituto G. Gaslini
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Padova
country: Italy
facility: Azienda Ospedaliera Universitaria di Padova
city: Roma
country: Italy
facility: Osp. Pediatrico Bambin Gesù
city: Rotterdam
country: Netherlands
facility: Erasmus MC - Sophia Kinderziekenhuis
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Infantil Universitario Niño Jesus
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
city: London
country: United Kingdom
facility: Great Ormond Street Hospital
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital
city: Sutton
country: United Kingdom
facility: The Royal Marsden Hospital
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Andrade RC, Boroni M, Amazonas MK, Vargas FR. New drug candidates for osteosarcoma: Drug repurposing based on gene expression signature. Comput Biol Med. 2021 Jul;134:104470. doi: 10.1016/j.compbiomed.2021.104470. Epub 2021 May 7.