Neuroectodermal TumorsPhase 1/2NCT02372006
Trial of Afatinib in Pediatric Tumours
A Phase 1/2 study testing afatinib in people with Neuroectodermal Tumors and Rhabdomyosarcoma, run by Boehringer Ingelheim at 28 sites in 12 countries.
Trial 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 Read more about this study
- Who is it for?
- Ages 1 year to 18 years
- Conditions the study is for
- Neuroectodermal Tumors, Rhabdomyosarcoma
- What is being tested?
- afatinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 28 sitesin 12 countries
- Study dates
- 29 Apr 2015to 5 Aug 2020
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- relevant toxicity from previous treatment
- known pre-existing relevant cardiac , hepatic, renal, bone marrow dysfunction, ILD, keratitis
- Further exclusion criteria apply
Trial locations and contacts
28 sites in 12 countries.
28 sites in 12 countries
France5 sites
HOP Pellegrin
Bordeaux, 33076
CTR Oscar Lambret
Lille, 59020
CTR Leon Berard
Lyon, 69008
INS Curie
Paris, 75248
INS Gustave Roussy
Villejuif, 94805
Italy4 sites
Istituto G. Gaslini
Genova, 16147
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, 20133
Azienda Ospedaliera Universitaria di Padova
Padova, 35128
Osp. Pediatrico Bambin Gesù
Roma, 00165
United Kingdom4 sites
Birmingham Children's Hospital
Birmingham, B4 6NH
Great Ormond Street Hospital
London, WC1N 3BN
Royal Manchester Children's Hospital
Manchester, M13 9WL
The Royal Marsden Hospital
Sutton, SM2 5PT
United States3 sites
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
The University of Texas Health Science Center at Houston
Houston, Texas, 77030
University of Wisconsin
Madison, Wisconsin, 53792
Germany3 sites
Charité - Universitätsmedizin Berlin
Berlin, 13353
Universitätsklinikum Essen AöR
Essen, 45147
Universitätsklinikum Tübingen
Tübingen, 72076
Austria2 sites
AKH - Medical University of Vienna
Vienna, 1090
St. Anna Children-Hospital, Children's Cancer Research, Wien
Vienna, 1090
Spain2 sites
Hospital Vall d'Hebron
Barcelona, 08035
Hospital Infantil Universitario Niño Jesus
Madrid, 28009
Denmark1 site
Rigshospitalet, København, Børneonkologisk Afsnit 5002
København Ø, 2100
Faroe Islands1 site
HOP Toulouse, Pédiat, Toulouse
Toulouse, 31059
About this study
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
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
- Conditions
- Neuroectodermal Tumors, Rhabdomyosarcoma
- Being tested
- afatinib
- Medical subject headings
- Neuroectodermal Tumors, Rhabdomyosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
afatinibDrug
| Study group | Role | What they receive |
|---|---|---|
| afatinib | Experimental | dose escalation Receives: Drug: afatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Assessed every 8 weeks until progression of disease, up to 336 days.
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.
Measured: 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.
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.
Measured: 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.
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.
Measured: During the first course (28 days) of treatment.
Secondary outcomes (10)
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.
Measured: Assessed every 8 weeks until progression of disease, up to 336 days.
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.
Measured: From the first treatment until date of first progression or death, up to 336 days.
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.
Measured: 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.
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.
Measured: 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.
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.
Measured: 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.
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.
Measured: 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.
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.
Measured: 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.
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.
Measured: From first documented response until the earliest of disease progression or death, up to 336 days.
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.
Measured: 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.
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.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2015 (estimated)
- Study start29 Apr 2015
- Primary completion5 Aug 2020
- Study completion5 Aug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Neuroectodermal TumorsStudies of the same condition, open and under way.
- More trials run by Boehringer IngelheimThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Boehringer Ingelheim, Study chair, Boehringer Ingelheim
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02372006
- Sponsor's protocol ID
- 1200.120
- Other IDs
- 2014-002123-10, 2014
- Status last verified
- Mar 2021
- First submitted
- 24 Feb 2015
- Last updated
- 4 Mar 2021
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Geoerger B, Marshall LV, Nysom K, Makin G, Bouffet E, Defachelles AS, Amoroso L, Aerts I, Leblond P, Barahona P, Van-Vlerken K, Fu E, Solca F, Lorence RM, Ziegler DS. Afatinib in paediatric patients with recurrent/refractory ErbB-dysregulated tumours: Results of a phase I/expansion trial. Eur J Cancer. 2023 Jul;188:8-19. doi: 10.1016/j.ejca.2023.04.007. Epub 2023 Apr 20.
PubMed 37178647Andrade 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.
PubMed 34004576
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02372006
- Acronym / sponsor ID
- 1200.120
- Conditions
- Neuroectodermal Tumors, Rhabdomyosarcoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- 29 Apr 2015 (actual)
- Primary completion
- 5 Aug 2020 (actual)
- Study completion
- 5 Aug 2020 (actual)
- First posted
- 26 Feb 2015 (estimated)
- Results
- Posted 4 Mar 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| afatinib | Experimental | Drug: afatinibdose escalation |
Who may qualify
- Ages
- 1 year to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- 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)
Key exclusion criteria (3 listed)
- relevant toxicity from previous treatment
- known pre-existing relevant cardiac , hepatic, renal, bone marrow dysfunction, ILD, keratitis
- Further exclusion criteria apply
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| afatinib | Drug | afatinib |
Primary outcome
Number of Participants With Objective Response - Maximum Tolerated Dose Expansion (MTD) Cohort
Time frame: Assessed every 8 weeks until progression of disease, up to 336 days.
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
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.
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
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.
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
Time frame: During the first course (28 days) of treatment.
Number of participants with Dose Limiting Toxicity adverse events for Dose finding part was reported.
10 secondary outcomes
Number of Participants With Objective Response - Dose Finding Part
Time frame: Assessed every 8 weeks until progression of disease, up to 336 days.
Progression Free Survival - Maximum Tolerated Dose (MTD) Expansion Cohort
Time frame: From the first treatment until date of first progression or death, up to 336 days.
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
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.
Maximum Measured Concentration (Cmax) - Dose Finding Part/Maximum Tolerated Dose (MTD) Expansion Cohort
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.
Time From (Last) Dosing to the Maximum Measured Concentration (Tmax) - Dose Finding Part/Maximum Tolerated Dose (MTD) Expansion Cohort
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.
Time From (Last) Dosing to the Maximum Measured Concentration at Steady State (Tmax,ss) - Dose Finding Part/Maximum Tolerated Dose (MTD) Expansion Cohort
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.
Accumulation (or Effective) Half-life - Dose Finding Part/Maximum Tolerated Dose (MTD) Expansion Cohort
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.
Duration of Objective Response - Maximum Tolerated Dose (MTD) Expansion Cohort
Time frame: From first documented response until the earliest of disease progression or death, up to 336 days.
Area Under the Curve Over Dosing Interval τ at Steady State (AUCτ,ss) - Maximum Tolerated Dose (MTD) Expansion Cohort
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.
Maximum Measured Concentration of the Analyte in Plasma at Steady State (Cmax,ss) - Maximum Tolerated Dose (MTD) Expansion Cohort
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37178647Geoerger B, Marshall LV, Nysom K, Makin G, Bouffet E, Defachelles AS, Amoroso L, Aerts I, Leblond P, Barahona P, Van-Vlerken K, Fu E, Solca F, Lorence RM, Ziegler DS. Afatinib in paediatric patients with recurrent/refractory ErbB-dysregulated tumours: Results of a phase I/expansion trial. Eur J Cancer. 2023 Jul;188:8-19. doi: 10.1016/j.ejca.2023.04.007. Epub 2023 Apr 20.
- Derived from this study: PubMed 34004576Andrade 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.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Boehringer Ingelheim study chair
Boehringer Ingelheim
28 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing afatinib in people with Neuroectodermal Tumors and Rhabdomyosarcoma, run by Boehringer Ingelheim at 28 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 28 sites in France, Italy, United Kingdom, United States, Germany and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Mar 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Objective Response - Maximum Tolerated Dose Expansion (MTD) Cohort (time frame: Assessed every 8 weeks until progression of disease, up to 336 days.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02372006, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2021.