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Trial of Afatinib in Pediatric Tumours

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ClinicalTrials.gov Identifier: NCT02372006
Recruitment Status : Completed
First Posted : February 26, 2015
Results First Posted : March 4, 2021
Last Update Posted : March 4, 2021
Sponsor:
Information provided by (Responsible Party):
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

Condition or disease Intervention/treatment Phase
Neuroectodermal Tumors Rhabdomyosarcoma Drug: afatinib Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 56 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : April 29, 2015
Actual Primary Completion Date : August 5, 2020
Actual Study Completion Date : August 5, 2020


Arm Intervention/treatment
Experimental: afatinib
dose escalation
Drug: afatinib



Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.


Secondary Outcome Measures :
  1. Number of Participants With Objective Response - Dose Finding Part [ Time Frame: 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.

  2. 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. ]
    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.

  3. 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. ]
    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.

  4. 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. ]
    Maximum measured concentration (Cmax) for Dose finding part/maximum tolerated dose (MTD) expansion cohort was reported.

  5. 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 (tmax) for Dose finding part/maximum tolerated dose (MTD) expansion cohort was reported.

  6. 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. ]
    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.

  7. 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. ]
    Accumulation (or effective) half-life for Dose finding part/maximum tolerated dose (MTD) expansion cohort was reported.

  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. ]
    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.

  9. 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. ]
    Area under the curve over dosing interval τ at steady state (AUCτ,ss) in maximum tolerated dose (MTD) expansion cohort was reported.

  10. 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. ]
    Maximum measured concentration of the analyte in plasma at steady state (Cmax,ss) in maximum tolerated dose (MTD) expansion cohort was reported.



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Ages Eligible for Study:   1 Year to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02372006


Locations
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Sponsors and Collaborators
Boehringer Ingelheim
Investigators
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Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  Study Documents (Full-Text)

Documents provided by Boehringer Ingelheim:
Statistical Analysis Plan  [PDF] July 31, 2020
Study Protocol  [PDF] June 2, 2017

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT02372006    
Other Study ID Numbers: 1200.120
2014-002123-10 ( EudraCT Number )
First Posted: February 26, 2015    Key Record Dates
Results First Posted: March 4, 2021
Last Update Posted: March 4, 2021
Last Verified: March 2021
Additional relevant MeSH terms:
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Rhabdomyosarcoma
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Myosarcoma
Neoplasms, Muscle Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Sarcoma
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neoplasms, Glandular and Epithelial
Afatinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action