Trial of Afatinib in Pediatric Tumours

NCT02372006 | Completed Phase 1 Results

• 2 other identifiers: 1200.1202014-002123-10
• Study Type: interventional
• Target: 56
• Locations: 11 countries
• Sites: 27

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. 1.Dose finding part to determine the MTD
2. 2.Biomarker specific MTD expansion cohort/Phase II part to assess clinical anti-tumour activity in included tumour types

Conditions

Neuroectodermal Tumors; Rhabdomyosarcoma

Outcome Measures

Primary Outcomes (4)

• 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.

• 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.

  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.

  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.

  During the first course (28 days) of treatment.

Secondary Outcomes (10)

• Number of Participants With Objective Response - Dose Finding Part

  Assessed every 8 weeks until progression of disease, up to 336 days.

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

  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

  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

  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

  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.

Study Arms (1)

afatinib

EXPERIMENTAL

dose escalation

Drug: afatinib

Interventions

afatinib DRUG

afatinib

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• relevant toxicity from previous treatment
• known pre-existing relevant cardiac , hepatic, renal, bone marrow dysfunction, ILD, keratitis

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (28)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Sydney Childrens Hospital

Randwick, New South Wales, 2031, Australia

Location

AKH - Medical University of Vienna

Vienna, 1090, Austria

Location

St. Anna Children-Hospital, Children's Cancer Research, Wien

Vienna, 1090, Austria

Location

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Rigshospitalet, København, Børneonkologisk Afsnit 5002

København Ø, 2100, Denmark

Location

HOP Toulouse, Pédiat, Toulouse

Toulouse, 31059, Faroe Islands

Location

HOP Pellegrin

Bordeaux, 33076, France

Location

CTR Oscar Lambret

Lille, 59020, France

Location

CTR Leon Berard

Lyon, 69008, France

Location

INS Curie

Paris, 75248, France

Location

INS Gustave Roussy

Villejuif, 94805, France

Location

Charité - Universitätsmedizin Berlin

Berlin, 13353, Germany

Location

Universitätsklinikum Essen AöR

Essen, 45147, Germany

Location

Universitätsklinikum Tübingen

Tübingen, 72076, Germany

Location

Istituto G. Gaslini

Genova, 16147, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Azienda Ospedaliera Universitaria di Padova

Padua, 35128, Italy

Location

Osp. Pediatrico Bambin Gesù

Roma, 00165, Italy

Location

Erasmus MC - Sophia Kinderziekenhuis

Rotterdam, 3015 CN, Netherlands

Location

Hospital Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Infantil Universitario Niño Jesus

Madrid, 28009, Spain

Location

Birmingham Children's Hospital

Birmingham, B4 6NH, United Kingdom

Location

Great Ormond Street Hospital

London, WC1N 3BN, United Kingdom

Location

Royal Manchester Children's Hospital

Manchester, M13 9WL, United Kingdom

Location

The Royal Marsden Hospital

Sutton, SM2 5PT, United Kingdom

Location

Related Publications (2)

• 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 DERIVED

• 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 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Neuroectodermal Tumors; Rhabdomyosarcoma

Interventions

Afatinib

Condition Hierarchy (Ancestors)

Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Myosarcoma; Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Sarcoma

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2015
• First Posted: February 26, 2015
• Study Start: April 29, 2015
• Primary Completion: August 5, 2020
• Study Completion: August 5, 2020
• Last Updated: March 4, 2021
• Results First Posted: March 4, 2021

Record last verified: 2021-03

Locations

IT (4); ES (2); DE (3); NL (1); FR (5); GB (4); US (3); CA (1); DK (1); AU (2); FA (1)