Trial Review

The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02372006




Registration number
NCT02372006
Ethics application status
Date submitted
24/02/2015
Date registered
26/02/2015
Date last updated
4/03/2021

Titles & IDs
Public title
Trial of Afatinib in Pediatric Tumours
Scientific 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
Secondary ID [1] 0 0
2014-002123-10
Secondary ID [2] 0 0
1200.120
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neuroectodermal Tumors 0 0
Rhabdomyosarcoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue
Cancer 0 0 0 0
Bone
Cancer 0 0 0 0
Children's - Other
Cancer 0 0 0 0
Neuroendocrine tumour (NET)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental: afatinib - dose escalation
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Objective Response - Maximum Tolerated Dose Expansion (MTD) Cohort
Timepoint [1] 0 0
Assessed every 8 weeks until progression of disease, up to 336 days.
Primary outcome [2] 0 0
Area Under the Curve Over Dosing Interval t at Steady State (AUCt,ss) - Dose Finding Part
Timepoint [2] 0 0
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.
Primary outcome [3] 0 0
Maximum Measured Concentration of the Analyte in Plasma at Steady State (Cmax,ss) - Dose Finding Part
Timepoint [3] 0 0
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.
Primary outcome [4] 0 0
Number of Participants With Dose Limiting Toxicity Adverse Events - Dose Finding Part
Timepoint [4] 0 0
During the first course (28 days) of treatment.
Secondary outcome [1] 0 0
Number of Participants With Objective Response - Dose Finding Part
Timepoint [1] 0 0
Assessed every 8 weeks until progression of disease, up to 336 days.
Secondary outcome [2] 0 0
Progression Free Survival - Maximum Tolerated Dose (MTD) Expansion Cohort
Timepoint [2] 0 0
From the first treatment until date of first progression or death, up to 336 days.
Secondary outcome [3] 0 0
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
Timepoint [3] 0 0
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.
Secondary outcome [4] 0 0
Maximum Measured Concentration (Cmax) - Dose Finding Part/Maximum Tolerated Dose (MTD) Expansion Cohort
Timepoint [4] 0 0
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.
Secondary outcome [5] 0 0
Time From (Last) Dosing to the Maximum Measured Concentration (Tmax) - Dose Finding Part/Maximum Tolerated Dose (MTD) Expansion Cohort
Timepoint [5] 0 0
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.
Secondary outcome [6] 0 0
Time From (Last) Dosing to the Maximum Measured Concentration at Steady State (Tmax,ss) - Dose Finding Part/Maximum Tolerated Dose (MTD) Expansion Cohort
Timepoint [6] 0 0
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.
Secondary outcome [7] 0 0
Accumulation (or Effective) Half-life - Dose Finding Part/Maximum Tolerated Dose (MTD) Expansion Cohort
Timepoint [7] 0 0
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.
Secondary outcome [8] 0 0
Duration of Objective Response - Maximum Tolerated Dose (MTD) Expansion Cohort
Timepoint [8] 0 0
From first documented response until the earliest of disease progression or death, up to 336 days.
Secondary outcome [9] 0 0
Area Under the Curve Over Dosing Interval t at Steady State (AUCt,ss) - Maximum Tolerated Dose (MTD) Expansion Cohort
Timepoint [9] 0 0
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.
Secondary outcome [10] 0 0
Maximum Measured Concentration of the Analyte in Plasma at Steady State (Cmax,ss) - Maximum Tolerated Dose (MTD) Expansion Cohort
Timepoint [10] 0 0
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.

Eligibility
Key inclusion 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
Minimum age
1 Year
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

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

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
29/04/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
5/08/2020
Sample size
Target
Accrual to date
Final
56
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Sydney Childrens Hospital - Randwick
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Massachusetts
Country [2] 0 0
United States of America
State/province [2] 0 0
Texas
Country [3] 0 0
United States of America
State/province [3] 0 0
Wisconsin
Country [4] 0 0
Austria
State/province [4] 0 0
Vienna
Country [5] 0 0
Austria
State/province [5] 0 0
Wien
Country [6] 0 0
Canada
State/province [6] 0 0
Ontario
Country [7] 0 0
Denmark
State/province [7] 0 0
København Ø
Country [8] 0 0
Faroe Islands
State/province [8] 0 0
Toulouse
Country [9] 0 0
France
State/province [9] 0 0
Bordeaux
Country [10] 0 0
France
State/province [10] 0 0
Lille
Country [11] 0 0
France
State/province [11] 0 0
Lyon
Country [12] 0 0
France
State/province [12] 0 0
Paris
Country [13] 0 0
France
State/province [13] 0 0
Villejuif
Country [14] 0 0
Germany
State/province [14] 0 0
Berlin
Country [15] 0 0
Germany
State/province [15] 0 0
Essen
Country [16] 0 0
Germany
State/province [16] 0 0
Tübingen
Country [17] 0 0
Italy
State/province [17] 0 0
Genova
Country [18] 0 0
Italy
State/province [18] 0 0
Milano
Country [19] 0 0
Italy
State/province [19] 0 0
Padova
Country [20] 0 0
Italy
State/province [20] 0 0
Roma
Country [21] 0 0
Netherlands
State/province [21] 0 0
Rotterdam
Country [22] 0 0
Spain
State/province [22] 0 0
Barcelona
Country [23] 0 0
Spain
State/province [23] 0 0
Madrid
Country [24] 0 0
United Kingdom
State/province [24] 0 0
Birmingham
Country [25] 0 0
United Kingdom
State/province [25] 0 0
London
Country [26] 0 0
United Kingdom
State/province [26] 0 0
Manchester
Country [27] 0 0
United Kingdom
State/province [27] 0 0
Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Boehringer Ingelheim
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Boehringer Ingelheim
Address 0 0
Boehringer Ingelheim
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT02372006