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Trial of Afatinib in Pediatric Tumours

Primary Purpose

Neuroectodermal Tumors, Rhabdomyosarcoma

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
afatinib
Sponsored by
Boehringer Ingelheim
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neuroectodermal Tumors

Eligibility Criteria

1 Year - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Dana-Farber Cancer Institute
  • The University of Texas Health Science Center at Houston
  • University of Wisconsin
  • Sydney Childrens Hospital
  • AKH - Medical University of Vienna
  • St. Anna Children-Hospital, Children's Cancer Research, Wien
  • The Hospital for Sick Children
  • Rigshospitalet, København, Børneonkologisk Afsnit 5002
  • HOP Toulouse, Pédiat, Toulouse
  • HOP Pellegrin
  • CTR Oscar Lambret
  • CTR Leon Berard
  • INS Curie
  • INS Gustave Roussy
  • Charité - Universitätsmedizin Berlin
  • Universitätsklinikum Essen AöR
  • Universitätsklinikum Tübingen
  • Istituto G. Gaslini
  • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Azienda Ospedaliera Universitaria di Padova
  • Osp. Pediatrico Bambin Gesù
  • Erasmus MC - Sophia Kinderziekenhuis
  • Hospital Vall d'Hebron
  • Hospital Infantil Universitario Niño Jesus
  • Birmingham Children's Hospital
  • Great Ormond Street Hospital
  • Royal Manchester Children's Hospital
  • The Royal Marsden Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

afatinib

Arm Description

dose escalation

Outcomes

Primary Outcome Measures

Number of Participants With Objective Response - Maximum Tolerated Dose Expansion (MTD) Cohort
Number of participants with objective response for maximum tolerated dose expansion (MTD) cohort was reported. The objective response was defined as a best overall response of complete response or partial response based on investigator's assessment according to the institutional response evaluation criteria for the given tumour type, assessed every 8 weeks until progression.
Area Under the Curve Over Dosing Interval τ at Steady State (AUCτ,ss) - Dose Finding Part
Area under the curve over dosing interval τ at steady state (AUCτ,ss) for Dose finding part was reported.
Maximum Measured Concentration of the Analyte in Plasma at Steady State (Cmax,ss) - Dose Finding Part
Maximum measured concentration of the analyte in plasma at steady state (Cmax,ss) for Dose finding part was reported.
Number of Participants With Dose Limiting Toxicity Adverse Events - Dose Finding Part
Number of participants with Dose Limiting Toxicity adverse events for Dose finding part was reported.

Secondary Outcome Measures

Number of Participants With Objective Response - Dose Finding Part
Number of participants with objective response for Dose finding part was reported. The objective response was defined as a best overall response of complete response or partial response based on investigator's assessment according to the institutional response evaluation criteria for the given tumour type, assessed every 8 weeks until progression.
Progression Free Survival - Maximum Tolerated Dose (MTD) Expansion Cohort
Progression free survival for the MTD expansion cohorts was reported. Progression free survival (PFS) was defined as the duration from the date of first treatment until the date of the first documented progression or death due to any cause. If a patient did not have an event, PFS was censored at the date of last adequate tumour assessment.
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
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 24 hours (AUC0-24) for Dose finding part was reported.
Maximum Measured Concentration (Cmax) - Dose Finding Part/Maximum Tolerated Dose (MTD) Expansion Cohort
Maximum measured concentration (Cmax) for Dose finding part/maximum tolerated dose (MTD) expansion cohort was reported.
Time From (Last) Dosing to the Maximum Measured Concentration (Tmax) - Dose Finding Part/Maximum Tolerated Dose (MTD) Expansion Cohort
Time from (last) dosing to the maximum measured concentration (tmax) for Dose finding part/maximum tolerated dose (MTD) expansion cohort was reported.
Time From (Last) Dosing to the Maximum Measured Concentration at Steady State (Tmax,ss) - Dose Finding Part/Maximum Tolerated Dose (MTD) Expansion Cohort
Time from (last) dosing to the maximum measured concentration at steady state (tmax,ss) for Dose finding part/maximum tolerated dose (MTD) expansion cohort was reported.
Accumulation (or Effective) Half-life - Dose Finding Part/Maximum Tolerated Dose (MTD) Expansion Cohort
Accumulation (or effective) half-life for Dose finding part/maximum tolerated dose (MTD) expansion cohort was reported.
Duration of Objective Response - Maximum Tolerated Dose (MTD) Expansion Cohort
Duration of objective response in maximum tolerated dose expansion (MTD) cohort was reported. The objective response was defined as a best overall response of complete response or partial response based on investigator's assessment according to the institutional response evaluation criteria for the given tumour type, assessed every 8 weeks until progression.
Area Under the Curve Over Dosing Interval τ at Steady State (AUCτ,ss) - Maximum Tolerated Dose (MTD) Expansion Cohort
Area under the curve over dosing interval τ at steady state (AUCτ,ss) in maximum tolerated dose (MTD) expansion cohort was reported.
Maximum Measured Concentration of the Analyte in Plasma at Steady State (Cmax,ss) - Maximum Tolerated Dose (MTD) Expansion Cohort
Maximum measured concentration of the analyte in plasma at steady state (Cmax,ss) in maximum tolerated dose (MTD) expansion cohort was reported.

Full Information

First Posted
February 24, 2015
Last Updated
March 3, 2021
Sponsor
Boehringer Ingelheim
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1. Study Identification

Unique Protocol Identification Number
NCT02372006
Brief Title
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

2. Study Status

Record Verification Date
March 2021
Overall Recruitment Status
Completed
Study Start Date
April 29, 2015 (Actual)
Primary Completion Date
August 5, 2020 (Actual)
Study Completion Date
August 5, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boehringer Ingelheim

4. Oversight

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuroectodermal Tumors, Rhabdomyosarcoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
56 (Actual)

8. Arms, Groups, and Interventions

Arm Title
afatinib
Arm Type
Experimental
Arm Description
dose escalation
Intervention Type
Drug
Intervention Name(s)
afatinib
Primary Outcome Measure Information:
Title
Number of Participants With Objective Response - Maximum Tolerated Dose Expansion (MTD) Cohort
Description
Number of participants with objective response for maximum tolerated dose expansion (MTD) cohort was reported. The objective response was defined as a best overall response of complete response or partial response based on investigator's assessment according to the institutional response evaluation criteria for the given tumour type, assessed every 8 weeks until progression.
Time Frame
Assessed every 8 weeks until progression of disease, up to 336 days.
Title
Area Under the Curve Over Dosing Interval τ at Steady State (AUCτ,ss) - Dose Finding Part
Description
Area under the curve over dosing interval τ at steady state (AUCτ,ss) for Dose finding part was reported.
Time Frame
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.
Title
Maximum Measured Concentration of the Analyte in Plasma at Steady State (Cmax,ss) - Dose Finding Part
Description
Maximum measured concentration of the analyte in plasma at steady state (Cmax,ss) for Dose finding part was reported.
Time Frame
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.
Title
Number of Participants With Dose Limiting Toxicity Adverse Events - Dose Finding Part
Description
Number of participants with Dose Limiting Toxicity adverse events for Dose finding part was reported.
Time Frame
During the first course (28 days) of treatment.
Secondary Outcome Measure Information:
Title
Number of Participants With Objective Response - Dose Finding Part
Description
Number of participants with objective response for Dose finding part was reported. The objective response was defined as a best overall response of complete response or partial response based on investigator's assessment according to the institutional response evaluation criteria for the given tumour type, assessed every 8 weeks until progression.
Time Frame
Assessed every 8 weeks until progression of disease, up to 336 days.
Title
Progression Free Survival - Maximum Tolerated Dose (MTD) Expansion Cohort
Description
Progression free survival for the MTD expansion cohorts was reported. Progression free survival (PFS) was defined as the duration from the date of first treatment until the date of the first documented progression or death due to any cause. If a patient did not have an event, PFS was censored at the date of last adequate tumour assessment.
Time Frame
From the first treatment until date of first progression or death, up to 336 days.
Title
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
Description
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 24 hours (AUC0-24) for Dose finding part was reported.
Time Frame
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.
Title
Maximum Measured Concentration (Cmax) - Dose Finding Part/Maximum Tolerated Dose (MTD) Expansion Cohort
Description
Maximum measured concentration (Cmax) for Dose finding part/maximum tolerated dose (MTD) expansion cohort was reported.
Time Frame
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.
Title
Time From (Last) Dosing to the Maximum Measured Concentration (Tmax) - Dose Finding Part/Maximum Tolerated Dose (MTD) Expansion Cohort
Description
Time from (last) dosing to the maximum measured concentration (tmax) for Dose finding part/maximum tolerated dose (MTD) expansion cohort was reported.
Time Frame
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.
Title
Time From (Last) Dosing to the Maximum Measured Concentration at Steady State (Tmax,ss) - Dose Finding Part/Maximum Tolerated Dose (MTD) Expansion Cohort
Description
Time from (last) dosing to the maximum measured concentration at steady state (tmax,ss) for Dose finding part/maximum tolerated dose (MTD) expansion cohort was reported.
Time Frame
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.
Title
Accumulation (or Effective) Half-life - Dose Finding Part/Maximum Tolerated Dose (MTD) Expansion Cohort
Description
Accumulation (or effective) half-life for Dose finding part/maximum tolerated dose (MTD) expansion cohort was reported.
Time Frame
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.
Title
Duration of Objective Response - Maximum Tolerated Dose (MTD) Expansion Cohort
Description
Duration of objective response in maximum tolerated dose expansion (MTD) cohort was reported. The objective response was defined as a best overall response of complete response or partial response based on investigator's assessment according to the institutional response evaluation criteria for the given tumour type, assessed every 8 weeks until progression.
Time Frame
From first documented response until the earliest of disease progression or death, up to 336 days.
Title
Area Under the Curve Over Dosing Interval τ at Steady State (AUCτ,ss) - Maximum Tolerated Dose (MTD) Expansion Cohort
Description
Area under the curve over dosing interval τ at steady state (AUCτ,ss) in maximum tolerated dose (MTD) expansion cohort was reported.
Time Frame
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.
Title
Maximum Measured Concentration of the Analyte in Plasma at Steady State (Cmax,ss) - Maximum Tolerated Dose (MTD) Expansion Cohort
Description
Maximum measured concentration of the analyte in plasma at steady state (Cmax,ss) in maximum tolerated dose (MTD) expansion cohort was reported.
Time Frame
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.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Boehringer Ingelheim
Organizational Affiliation
Boehringer Ingelheim
Official's Role
Study Chair
Facility Information:
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
The University of Texas Health Science Center at Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Wisconsin
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Facility Name
Sydney Childrens Hospital
City
Randwick
State/Province
New South Wales
ZIP/Postal Code
2031
Country
Australia
Facility Name
AKH - Medical University of Vienna
City
Vienna
ZIP/Postal Code
1090
Country
Austria
Facility Name
St. Anna Children-Hospital, Children's Cancer Research, Wien
City
Wien
ZIP/Postal Code
1090
Country
Austria
Facility Name
The Hospital for Sick Children
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X8
Country
Canada
Facility Name
Rigshospitalet, København, Børneonkologisk Afsnit 5002
City
København Ø
ZIP/Postal Code
2100
Country
Denmark
Facility Name
HOP Toulouse, Pédiat, Toulouse
City
Toulouse
ZIP/Postal Code
31059
Country
Faroe Islands
Facility Name
HOP Pellegrin
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Facility Name
CTR Oscar Lambret
City
Lille
ZIP/Postal Code
59020
Country
France
Facility Name
CTR Leon Berard
City
Lyon
ZIP/Postal Code
69008
Country
France
Facility Name
INS Curie
City
Paris
ZIP/Postal Code
75248
Country
France
Facility Name
INS Gustave Roussy
City
Villejuif
ZIP/Postal Code
94805
Country
France
Facility Name
Charité - Universitätsmedizin Berlin
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Universitätsklinikum Essen AöR
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Universitätsklinikum Tübingen
City
Tübingen
ZIP/Postal Code
72076
Country
Germany
Facility Name
Istituto G. Gaslini
City
Genova
ZIP/Postal Code
16147
Country
Italy
Facility Name
Fondazione IRCCS Istituto Nazionale dei Tumori
City
Milano
ZIP/Postal Code
20133
Country
Italy
Facility Name
Azienda Ospedaliera Universitaria di Padova
City
Padova
ZIP/Postal Code
35128
Country
Italy
Facility Name
Osp. Pediatrico Bambin Gesù
City
Roma
ZIP/Postal Code
00165
Country
Italy
Facility Name
Erasmus MC - Sophia Kinderziekenhuis
City
Rotterdam
ZIP/Postal Code
3015 CN
Country
Netherlands
Facility Name
Hospital Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Infantil Universitario Niño Jesus
City
Madrid
ZIP/Postal Code
28009
Country
Spain
Facility Name
Birmingham Children's Hospital
City
Birmingham
ZIP/Postal Code
B4 6NH
Country
United Kingdom
Facility Name
Great Ormond Street Hospital
City
London
ZIP/Postal Code
WC1N 3BN
Country
United Kingdom
Facility Name
Royal Manchester Children's Hospital
City
Manchester
ZIP/Postal Code
M13 9WL
Country
United Kingdom
Facility Name
The Royal Marsden Hospital
City
Sutton
ZIP/Postal Code
SM2 5PT
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
34004576
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.
Results Reference
derived
Links:
URL
http://www.mystudywindow.com
Description
Related Info

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Trial of Afatinib in Pediatric Tumours

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