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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/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
Treatment: Drugs - afatinib

Experimental: afatinib - dose escalation


Treatment: Drugs: afatinib
Intervention code [1] 0 0
Treatment: Drugs
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
N/A
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/Phase 2
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
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
Trial website
https://clinicaltrials.gov/ct2/show/NCT02372006
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02372006