Trial of Afatinib in Pediatric Tumours

Rhabdomyosarcoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02372006
• Other study ID #: 1200.120
• Secondary ID: 2014-002123-10
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: April 29, 2015
• Est. completion date: August 5, 2020

Study information

• Verified date: March 2021
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: August 5, 2020
• Est. primary completion date: August 5, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Neuroectodermal Tumors
• Neuroectodermal Tumors, Primitive
• Rhabdomyosarcoma

Intervention

Drug:
• afatinib

Locations

Country	Name	City	State
Australia	Sydney Childrens Hospital	Randwick	New South Wales
Austria	AKH - Medical University of Vienna	Vienna
Austria	St. Anna Children-Hospital, Children's Cancer Research, Wien	Wien
Canada	The Hospital for Sick Children	Toronto	Ontario
Denmark	Rigshospitalet, København, Børneonkologisk Afsnit 5002	København Ø
Faroe Islands	HOP Toulouse, Pédiat, Toulouse	Toulouse
France	HOP Pellegrin	Bordeaux
France	CTR Oscar Lambret	Lille
France	CTR Leon Berard	Lyon
France	INS Curie	Paris
France	INS Gustave Roussy	Villejuif
Germany	Charité - Universitätsmedizin Berlin	Berlin
Germany	Universitätsklinikum Essen AöR	Essen
Germany	Universitätsklinikum Tübingen	Tübingen
Italy	Istituto G. Gaslini	Genova
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano
Italy	Azienda Ospedaliera Universitaria di Padova	Padova
Italy	Osp. Pediatrico Bambin Gesù	Roma
Netherlands	Erasmus MC - Sophia Kinderziekenhuis	Rotterdam
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital Infantil Universitario Niño Jesus	Madrid
United Kingdom	Birmingham Children's Hospital	Birmingham
United Kingdom	Great Ormond Street Hospital	London
United Kingdom	Royal Manchester Children's Hospital	Manchester
United Kingdom	The Royal Marsden Hospital	Sutton
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	The University of Texas Health Science Center at Houston	Houston	Texas
United States	University of Wisconsin	Madison	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Canada,  Denmark,  Faroe Islands,  France,  Germany,  Italy,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Assessed every 8 weeks until progression of disease, up to 336 days.
Primary	Area Under the Curve Over Dosing Interval t at Steady State (AUCt,ss) - Dose Finding Part	Area under the curve over dosing interval t at steady state (AUCt,ss) for Dose finding part was reported.	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	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.	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	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.	During the first course (28 days) of treatment.
Secondary	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.	Assessed every 8 weeks until progression of disease, up to 336 days.
Secondary	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.	From the first treatment until date of first progression or death, up to 336 days.
Secondary	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.	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	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.	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	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.	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	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.	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	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.	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	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.	From first documented response until the earliest of disease progression or death, up to 336 days.
Secondary	Area Under the Curve Over Dosing Interval t at Steady State (AUCt,ss) - Maximum Tolerated Dose (MTD) Expansion Cohort	Area under the curve over dosing interval t at steady state (AUCt,ss) in maximum tolerated dose (MTD) expansion cohort was reported.	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	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.	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.

External Links

•   Related Info