NCT02372006 · CITED IN SOURCE DOCUMENTS

Trial of Afatinib in Pediatric Tumours

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE1, PHASE2
Status at capture: COMPLETED
Registry last update: 2021-03-04

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

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Number of Participants With Objective Response - Maximum Tolerated Dose Expansion (MTD) Cohort

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outcome · POSTED

Area Under the Curve Over Dosing Interval τ at Steady State (AUCτ,ss) - Dose Finding Part

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outcome · POSTED

Maximum Measured Concentration of the Analyte in Plasma at Steady State (Cmax,ss) - Dose Finding Part

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outcome · POSTED

Number of Participants With Dose Limiting Toxicity Adverse Events - Dose Finding Part

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outcome · POSTED

Number of Participants With Objective Response - Dose Finding Part

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outcome · POSTED

Progression Free Survival - Maximum Tolerated Dose (MTD) Expansion Cohort

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outcome · POSTED

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

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outcome · POSTED

Maximum Measured Concentration (Cmax) - Dose Finding Part/Maximum Tolerated Dose (MTD) Expansion Cohort

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outcome · POSTED

Time From (Last) Dosing to the Maximum Measured Concentration (Tmax) - Dose Finding Part/Maximum Tolerated Dose (MTD) Expansion Cohort

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outcome · POSTED

Time From (Last) Dosing to the Maximum Measured Concentration at Steady State (Tmax,ss) - Dose Finding Part/Maximum Tolerated Dose (MTD) Expansion Cohort

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outcome · POSTED

Accumulation (or Effective) Half-life - Dose Finding Part/Maximum Tolerated Dose (MTD) Expansion Cohort

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outcome · POSTED

Duration of Objective Response - Maximum Tolerated Dose (MTD) Expansion Cohort

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outcome · POSTED

Area Under the Curve Over Dosing Interval τ at Steady State (AUCτ,ss) - Maximum Tolerated Dose (MTD) Expansion Cohort

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outcome · POSTED

Maximum Measured Concentration of the Analyte in Plasma at Steady State (Cmax,ss) - Maximum Tolerated Dose (MTD) Expansion Cohort

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

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
healthy Volunteers: false
maximum Age: 18 Years
minimum Age: 1 Year
sex: ALL
std Ages: CHILD
ADULT

Treatment arms and interventions

arm Groups

description
dose escalation
intervention Names
Drug: afatinib
label
afatinib
type
EXPERIMENTAL

interventions

arm Group Labels
afatinib
name
afatinib
type
DRUG

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 56
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

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.
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.
description
Area under the curve over dosing interval τ at steady state (AUCτ,ss) for Dose finding part was reported.
measure
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.
description
Maximum measured concentration of the analyte in plasma at steady state (Cmax,ss) for Dose finding part was reported.
measure
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.
description
Number of participants with Dose Limiting Toxicity adverse events for Dose finding part was reported.
measure
Number of Participants With Dose Limiting Toxicity Adverse Events - Dose Finding Part
time Frame
During the first course (28 days) of treatment.

secondary Outcomes

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.
measure
Number of Participants With Objective Response - Dose Finding Part
time Frame
Assessed every 8 weeks until progression of disease, up to 336 days.
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.
measure
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.
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.
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
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.
description
Maximum measured concentration (Cmax) for Dose finding part/maximum tolerated dose (MTD) expansion cohort was reported.
measure
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.
description
Time from (last) dosing to the maximum measured concentration (tmax) for Dose finding part/maximum tolerated dose (MTD) expansion cohort was reported.
measure
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.
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.
measure
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.
description
Accumulation (or effective) half-life for Dose finding part/maximum tolerated dose (MTD) expansion cohort was reported.
measure
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.
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.
measure
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.
description
Area under the curve over dosing interval τ at steady state (AUCτ,ss) in maximum tolerated dose (MTD) expansion cohort was reported.
measure
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.
description
Maximum measured concentration of the analyte in plasma at steady state (Cmax,ss) in maximum tolerated dose (MTD) expansion cohort was reported.
measure
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.

Full 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: 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

Source references

references

citation
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.
pmid
37178647
type
DERIVED
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.
pmid
34004576
type
DERIVED