Trial of Afatinib in Pediatric Tumours
- Registration Number
- NCT02372006
- Lead Sponsor
- Boehringer Ingelheim
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 56
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description afatinib afatinib dose escalation
- Primary Outcome Measures
Name Time Method Number of Participants With Objective Response - Maximum Tolerated Dose Expansion (MTD) Cohort 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.
Number of Participants With Dose Limiting Toxicity Adverse Events - Dose Finding Part During the first course (28 days) of treatment. Number of participants with Dose Limiting Toxicity adverse events for Dose finding part was reported.
Area Under the Curve Over Dosing Interval τ at Steady State (AUCτ,ss) - Dose Finding Part 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 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.
- Secondary Outcome Measures
Name Time Method Time From (Last) Dosing to the Maximum Measured Concentration at Steady State (Tmax,ss) - Dose Finding Part/Maximum Tolerated Dose (MTD) Expansion Cohort 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. 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.
Accumulation (or Effective) Half-life - Dose Finding Part/Maximum Tolerated Dose (MTD) Expansion Cohort 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 for Dose finding part/maximum tolerated dose (MTD) expansion cohort was reported.
Progression Free Survival - Maximum Tolerated Dose (MTD) Expansion Cohort From the first treatment until date of first progression or death, up to 336 days. 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.
Maximum Measured Concentration (Cmax) - Dose Finding Part/Maximum Tolerated Dose (MTD) Expansion Cohort 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) for Dose finding part/maximum tolerated dose (MTD) expansion cohort was reported.
Maximum Measured Concentration of the Analyte in Plasma at Steady State (Cmax,ss) - Maximum Tolerated Dose (MTD) Expansion Cohort 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) in maximum tolerated dose (MTD) expansion cohort was reported.
Number of Participants With Objective Response - Dose Finding Part Assessed every 8 weeks until progression of disease, up to 336 days. 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.
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 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. 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.
Duration of Objective Response - Maximum Tolerated Dose (MTD) Expansion Cohort From first documented response until the earliest of disease progression or death, up to 336 days. 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.
Time From (Last) Dosing to the Maximum Measured Concentration (Tmax) - Dose Finding Part/Maximum Tolerated Dose (MTD) Expansion Cohort 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) for Dose finding part/maximum tolerated dose (MTD) expansion cohort was reported.
Area Under the Curve Over Dosing Interval τ at Steady State (AUCτ,ss) - Maximum Tolerated Dose (MTD) Expansion Cohort 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) in maximum tolerated dose (MTD) expansion cohort was reported.
Trial Locations
- Locations (28)
INS Curie
🇫🇷Paris, France
Sydney Childrens Hospital
🇦🇺Randwick, New South Wales, Australia
HOP Pellegrin
🇫🇷Bordeaux, France
St. Anna Children-Hospital, Children's Cancer Research, Wien
🇦🇹Wien, Austria
CTR Oscar Lambret
🇫🇷Lille, France
Osp. Pediatrico Bambin Gesù
🇮🇹Roma, Italy
Birmingham Children's Hospital
🇬🇧Birmingham, United Kingdom
The Royal Marsden Hospital
🇬🇧Sutton, United Kingdom
INS Gustave Roussy
🇫🇷Villejuif, France
Erasmus MC - Sophia Kinderziekenhuis
🇳🇱Rotterdam, Netherlands
Istituto G. Gaslini
🇮🇹Genova, Italy
Great Ormond Street Hospital
🇬🇧London, United Kingdom
Charité - Universitätsmedizin Berlin
🇩🇪Berlin, Germany
Universitätsklinikum Tübingen
🇩🇪Tübingen, Germany
Hospital Vall d'Hebron
🇪🇸Barcelona, Spain
Universitätsklinikum Essen AöR
🇩🇪Essen, Germany
Azienda Ospedaliera Universitaria di Padova
🇮🇹Padova, Italy
Hospital Infantil Universitario Niño Jesus
🇪🇸Madrid, Spain
Royal Manchester Children's Hospital
🇬🇧Manchester, United Kingdom
Rigshospitalet, København, Børneonkologisk Afsnit 5002
🇩🇰København Ø, Denmark
HOP Toulouse, Pédiat, Toulouse
🇫🇴Toulouse, Faroe Islands
The Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
CTR Leon Berard
🇫🇷Lyon, France
AKH - Medical University of Vienna
🇦🇹Vienna, Austria
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University of Wisconsin
🇺🇸Madison, Wisconsin, United States
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milano, Italy
The University of Texas Health Science Center at Houston
🇺🇸Houston, Texas, United States