Trial of Afatinib in Pediatric Tumours
Sponsor
Boehringer Ingelheim (Industry)
Overall Status
Completed
CT.gov ID
NCT02372006
Collaborator
(none)
56
28
1
63.2
2
0
Study Details
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:
-
Dose finding part to determine the MTD
-
Biomarker specific MTD expansion cohort/Phase II part to assess clinical anti-tumour activity in included tumour types
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Study Design
Study Type:
Interventional
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
:
Apr 29, 2015
Actual Primary Completion Date
:
Aug 5, 2020
Actual Study Completion Date
:
Aug 5, 2020
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: afatinib dose escalation |
Drug: afatinib
|
Outcome Measures
Primary Outcome Measures
- 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.
- 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.
- 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.
Secondary Outcome Measures
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
1 Year
to 18 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Dana-Farber Cancer Institute | Boston | Massachusetts | United States | 02215 |
| 2 | The University of Texas Health Science Center at Houston | Houston | Texas | United States | 77030 |
| 3 | University of Wisconsin | Madison | Wisconsin | United States | 53792 |
| 4 | Sydney Childrens Hospital | Randwick | New South Wales | Australia | 2031 |
| 5 | AKH - Medical University of Vienna | Vienna | Austria | 1090 | |
| 6 | St. Anna Children-Hospital, Children's Cancer Research, Wien | Wien | Austria | 1090 | |
| 7 | The Hospital for Sick Children | Toronto | Ontario | Canada | M5G 1X8 |
| 8 | Rigshospitalet, København, Børneonkologisk Afsnit 5002 | København Ø | Denmark | 2100 | |
| 9 | HOP Toulouse, Pédiat, Toulouse | Toulouse | Faroe Islands | 31059 | |
| 10 | HOP Pellegrin | Bordeaux | France | 33076 | |
| 11 | CTR Oscar Lambret | Lille | France | 59020 | |
| 12 | CTR Leon Berard | Lyon | France | 69008 | |
| 13 | INS Curie | Paris | France | 75248 | |
| 14 | INS Gustave Roussy | Villejuif | France | 94805 | |
| 15 | Charité - Universitätsmedizin Berlin | Berlin | Germany | 13353 | |
| 16 | Universitätsklinikum Essen AöR | Essen | Germany | 45147 | |
| 17 | Universitätsklinikum Tübingen | Tübingen | Germany | 72076 | |
| 18 | Istituto G. Gaslini | Genova | Italy | 16147 | |
| 19 | Fondazione IRCCS Istituto Nazionale dei Tumori | Milano | Italy | 20133 | |
| 20 | Azienda Ospedaliera Universitaria di Padova | Padova | Italy | 35128 | |
| 21 | Osp. Pediatrico Bambin Gesù | Roma | Italy | 00165 | |
| 22 | Erasmus MC - Sophia Kinderziekenhuis | Rotterdam | Netherlands | 3015 CN | |
| 23 | Hospital Vall d'Hebron | Barcelona | Spain | 08035 | |
| 24 | Hospital Infantil Universitario Niño Jesus | Madrid | Spain | 28009 | |
| 25 | Birmingham Children's Hospital | Birmingham | United Kingdom | B4 6NH | |
| 26 | Great Ormond Street Hospital | London | United Kingdom | WC1N 3BN | |
| 27 | Royal Manchester Children's Hospital | Manchester | United Kingdom | M13 9WL | |
| 28 | The Royal Marsden Hospital | Sutton | United Kingdom | SM2 5PT |
Sponsors and Collaborators
- Boehringer Ingelheim
Investigators
- Study Chair: Boehringer Ingelheim, Boehringer Ingelheim
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.Responsible Party:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT02372006
Other Study ID Numbers:
- 1200.120
- 2014-002123-10
First Posted:
Feb 26, 2015
Last Update Posted:
Mar 4, 2021
Last Verified:
Mar 1, 2021
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Phase I/II open label, dose escalation trial to determine the Maximum tolerated dose (MTD), safety, Pharmacokinetics (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. |
|---|---|
| Pre-assignment Detail | Only subjects that met all the study inclusion and none of the exclusion criteria were to be entered in the study. All subjects were free to withdraw from the clinical trial at any time for any reason given. Close monitoring of all subjects was adhered to throughout the trial conduct. Rescue medication was allowed for all patients as required. |
| Arm/Group Title | Dose Finding - Level 0 | Dose Finding - Level 1 | Maximum Tolerated Dose (MTD) Expansion Cohort - Level 0 |
|---|---|---|---|
| Arm/Group Description | Afatinib, dose level 0. (Once daily at 80% of the recommended adult dose per m2 body surface area [BSA] using allometric scaling): Oral solid single-unit film-coated tablets for pediatric patients who are able to swallow them. Oral liquid formulation for patients who cannot swallow the film-coated tablets, or for doses which cannot be achieved by the film-coated tablets, or for pediatric patients who did not accept the film-coated tablets. Therapy with afatinib continued as long as the individual patient benefited from the therapy, did not develop secondary malignancy, and did not meet one of the criteria requiring withdrawal from treatment. Afatinib in film-coated tablet form can be given in tablets of 20, 30, 40 and 50 mg. The dose in film-coated tablets is related to the free base equivalent to afatinib. The dose of afatinib as capsule and solvent for oral solution is given as a 200 mg capsule to be dissolved in aqueous solvent (2 capsules per 100 milliliter solvent) i.e. 4 milligram per milliliter. | Afatinib, dose level 1. (Once daily at 100% of the recommended adult dose per m2 body surface area [BSA] using allometric scaling): Oral solid single-unit film-coated tablets for pediatric patients who are able to swallow them. Oral liquid formulation for patients who cannot swallow the film-coated tablets, or for doses which cannot be achieved by the film-coated tablets, or for pediatric patients who did not accept the film-coated tablets. Therapy with afatinib continued as long as the individual patient benefited from the therapy, did not develop secondary malignancy, and did not meet one of the criteria requiring withdrawal from treatment. Afatinib in film-coated tablet form can be given in tablets of 20, 30, 40 and 50 mg. The dose in film-coated tablets is related to the free base equivalent to afatinib. The dose of afatinib as capsule and solvent for oral solution is given as a 200 mg capsule to be dissolved in aqueous solvent (2 capsules per 100 milliliter solvent) i.e. 4 milligram per milliliter. | Afatinib, dose level 0. (Once daily at 80% of the recommended adult dose per m2 body surface area [BSA] using allometric scaling): Oral solid single-unit film-coated tablets for pediatric patients who are able to swallow them. Oral liquid formulation for patients who cannot swallow the film-coated tablets, or for doses which cannot be achieved by the film-coated tablets, or for pediatric patients who did not accept the film-coated tablets. Therapy with afatinib continued as long as the individual patient benefited from the therapy, did not develop secondary malignancy, and did not meet one of the criteria requiring withdrawal from treatment. Afatinib in film-coated tablet form can be given in tablets of 20, 30, 40 and 50 mg. The dose in film-coated tablets is related to the free base equivalent to afatinib. The dose of afatinib as capsule and solvent for oral solution is given as a 200 mg capsule to be dissolved in aqueous solvent (2 capsules per 100 milliliter solvent) i.e. 4 milligram per milliliter. |
| Period Title: Overall Study | |||
| STARTED | 8 | 9 | 39 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 8 | 9 | 39 |
Baseline Characteristics
| Arm/Group Title | Dose Finding - Level 0 | Dose Finding - Level 1 | Maximum Tolerated Dose (MTD) Expansion Cohort - Level 0 | Total |
|---|---|---|---|---|
| Arm/Group Description | Afatinib, dose level 0. (Once daily at 80% of the recommended adult dose per m2 body surface area [BSA] using allometric scaling): Oral solid single-unit film-coated tablets for pediatric patients who are able to swallow them. Oral liquid formulation for patients who cannot swallow the film-coated tablets, or for doses which cannot be achieved by the film-coated tablets, or for pediatric patients who did not accept the film-coated tablets. Therapy with afatinib continued as long as the individual patient benefited from the therapy, did not develop secondary malignancy, and did not meet one of the criteria requiring withdrawal from treatment. Afatinib in film-coated tablet form can be given in tablets of 20, 30, 40 and 50 mg. The dose in film-coated tablets is related to the free base equivalent to afatinib. The dose of afatinib as capsule and solvent for oral solution is given as a 200 mg capsule to be dissolved in aqueous solvent (2 capsules per 100 milliliter solvent) i.e. 4 milligram per milliliter. | Afatinib, dose level 1. (Once daily at 100% of the recommended adult dose per m2 body surface area [BSA] using allometric scaling): Oral solid single-unit film-coated tablets for pediatric patients who are able to swallow them. Oral liquid formulation for patients who cannot swallow the film-coated tablets, or for doses which cannot be achieved by the film-coated tablets, or for pediatric patients who did not accept the film-coated tablets. Therapy with afatinib continued as long as the individual patient benefited from the therapy, did not develop secondary malignancy, and did not meet one of the criteria requiring withdrawal from treatment. Afatinib in film-coated tablet form can be given in tablets of 20, 30, 40 and 50 mg. The dose in film-coated tablets is related to the free base equivalent to afatinib. The dose of afatinib as capsule and solvent for oral solution is given as a 200 mg capsule to be dissolved in aqueous solvent (2 capsules per 100 milliliter solvent) i.e. 4 milligram per milliliter. | Afatinib, dose level 0. (Once daily at 80% of the recommended adult dose per m2 body surface area [BSA] using allometric scaling): Oral solid single-unit film-coated tablets for pediatric patients who are able to swallow them. Oral liquid formulation for patients who cannot swallow the film-coated tablets, or for doses which cannot be achieved by the film-coated tablets, or for pediatric patients who did not accept the film-coated tablets. Therapy with afatinib continued as long as the individual patient benefited from the therapy, did not develop secondary malignancy, and did not meet one of the criteria requiring withdrawal from treatment. Afatinib in film-coated tablet form can be given in tablets of 20, 30, 40 and 50 mg. The dose in film-coated tablets is related to the free base equivalent to afatinib. The dose of afatinib as capsule and solvent for oral solution is given as a 200 mg capsule to be dissolved in aqueous solvent (2 capsules per 100 milliliter solvent) i.e. 4 milligram per milliliter. | Total of all reporting groups |
| Overall Participants | 8 | 9 | 39 | 56 |
| Age (Years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Years] |
9.75
(4.83)
|
10.44
(5.29)
|
10.92
(4.44)
|
10.68
(4.57)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
4
50%
|
4
44.4%
|
16
41%
|
24
42.9%
|
| Male |
4
50%
|
5
55.6%
|
23
59%
|
32
57.1%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||
| Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Not Hispanic or Latino |
4
50%
|
5
55.6%
|
37
94.9%
|
46
82.1%
|
| Unknown or Not Reported |
4
50%
|
4
44.4%
|
2
5.1%
|
10
17.9%
|
| Race (NIH/OMB) (Count of Participants) | ||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
1
2.6%
|
1
1.8%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
2
5.1%
|
2
3.6%
|
| White |
3
37.5%
|
4
44.4%
|
29
74.4%
|
36
64.3%
|
| More than one race |
1
12.5%
|
0
0%
|
0
0%
|
1
1.8%
|
| Unknown or Not Reported |
4
50%
|
5
55.6%
|
7
17.9%
|
16
28.6%
|
Outcome Measures
| Title | Number of Participants With Objective Response - Maximum Tolerated Dose Expansion (MTD) Cohort |
|---|---|
| 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. |
| Time Frame | Assessed every 8 weeks until progression of disease, up to 336 days. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treated set (TS): This patient set included all patients enrolled in the trial who were documented to have taken at least one dose of study medication. |
| Arm/Group Title | Maximum Tolerated Dose (MTD) Expansion Cohort - Level 0 |
|---|---|
| Arm/Group Description | Afatinib, dose level 0. (Once daily at 80% of the recommended adult dose per m2 body surface area [BSA] using allometric scaling): Oral solid single-unit film-coated tablets for pediatric patients who are able to swallow them. Oral liquid formulation for patients who cannot swallow the film-coated tablets, or for doses which cannot be achieved by the film-coated tablets, or for pediatric patients who did not accept the film-coated tablets. Therapy with afatinib continued as long as the individual patient benefited from the therapy, did not develop secondary malignancy, and did not meet one of the criteria requiring withdrawal from treatment. Afatinib in film-coated tablet form can be given in tablets of 20, 30, 40 and 50 mg. The dose in film-coated tablets is related to the free base equivalent to afatinib. The dose of afatinib as capsule and solvent for oral solution is given as a 200 mg capsule to be dissolved in aqueous solvent (2 capsules per 100 milliliter solvent) i.e. 4 milligram per milliliter. |
| Measure Participants | 39 |
| Count of Participants [Participants] |
3
37.5%
|
| Title | Area Under the Curve Over Dosing Interval τ at Steady State (AUCτ,ss) - Dose Finding Part |
|---|---|
| Description | Area under the curve over dosing interval τ at steady state (AUCτ,ss) for Dose finding part was reported. |
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetics (PK) analysis set (PKS): This patient set included all patients in the TS who provided at least one PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Only participants with non-missing results were included in the analysis. |
| Arm/Group Title | Dose Finding - Level 0 | Dose Finding - Level 1 |
|---|---|---|
| Arm/Group Description | Afatinib, dose level 0. (Once daily at 80% of the recommended adult dose per m2 body surface area [BSA] using allometric scaling): Oral solid single-unit film-coated tablets for pediatric patients who are able to swallow them. Oral liquid formulation for patients who cannot swallow the film-coated tablets, or for doses which cannot be achieved by the film-coated tablets, or for pediatric patients who did not accept the film-coated tablets. Therapy with afatinib continued as long as the individual patient benefited from the therapy, did not develop secondary malignancy, and did not meet one of the criteria requiring withdrawal from treatment. Afatinib in film-coated tablet form can be given in tablets of 20, 30, 40 and 50 mg. The dose in film-coated tablets is related to the free base equivalent to afatinib. The dose of afatinib as capsule and solvent for oral solution is given as a 200 mg capsule to be dissolved in aqueous solvent (2 capsules per 100 milliliter solvent) i.e. 4 milligram per milliliter. | Afatinib, dose level 1. (Once daily at 100% of the recommended adult dose per m2 body surface area [BSA] using allometric scaling): Oral solid single-unit film-coated tablets for pediatric patients who are able to swallow them. Oral liquid formulation for patients who cannot swallow the film-coated tablets, or for doses which cannot be achieved by the film-coated tablets, or for pediatric patients who did not accept the film-coated tablets. Therapy with afatinib continued as long as the individual patient benefited from the therapy, did not develop secondary malignancy, and did not meet one of the criteria requiring withdrawal from treatment. Afatinib in film-coated tablet form can be given in tablets of 20, 30, 40 and 50 mg. The dose in film-coated tablets is related to the free base equivalent to afatinib. The dose of afatinib as capsule and solvent for oral solution is given as a 200 mg capsule to be dissolved in aqueous solvent (2 capsules per 100 milliliter solvent) i.e. 4 milligram per milliliter. |
| Measure Participants | 7 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [hours times nanogram per milliliter] |
681
(43.8)
|
1380
(29.0)
|
| Title | Maximum Measured Concentration of the Analyte in Plasma at Steady State (Cmax,ss) - Dose Finding Part |
|---|---|
| Description | Maximum measured concentration of the analyte in plasma at steady state (Cmax,ss) for Dose finding part was reported. |
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetics (PK) analysis set (PKS): This patient set included all patients in the TS who provided at least one PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Only participants with non-missing results were included in the analysis. |
| Arm/Group Title | Dose Finding - Level 0 | Dose Finding - Level 1 |
|---|---|---|
| Arm/Group Description | Afatinib, dose level 0. (Once daily at 80% of the recommended adult dose per m2 body surface area [BSA] using allometric scaling): Oral solid single-unit film-coated tablets for pediatric patients who are able to swallow them. Oral liquid formulation for patients who cannot swallow the film-coated tablets, or for doses which cannot be achieved by the film-coated tablets, or for pediatric patients who did not accept the film-coated tablets. Therapy with afatinib continued as long as the individual patient benefited from the therapy, did not develop secondary malignancy, and did not meet one of the criteria requiring withdrawal from treatment. Afatinib in film-coated tablet form can be given in tablets of 20, 30, 40 and 50 mg. The dose in film-coated tablets is related to the free base equivalent to afatinib. The dose of afatinib as capsule and solvent for oral solution is given as a 200 mg capsule to be dissolved in aqueous solvent (2 capsules per 100 milliliter solvent) i.e. 4 milligram per milliliter. | Afatinib, dose level 1. (Once daily at 100% of the recommended adult dose per m2 body surface area [BSA] using allometric scaling): Oral solid single-unit film-coated tablets for pediatric patients who are able to swallow them. Oral liquid formulation for patients who cannot swallow the film-coated tablets, or for doses which cannot be achieved by the film-coated tablets, or for pediatric patients who did not accept the film-coated tablets. Therapy with afatinib continued as long as the individual patient benefited from the therapy, did not develop secondary malignancy, and did not meet one of the criteria requiring withdrawal from treatment. Afatinib in film-coated tablet form can be given in tablets of 20, 30, 40 and 50 mg. The dose in film-coated tablets is related to the free base equivalent to afatinib. The dose of afatinib as capsule and solvent for oral solution is given as a 200 mg capsule to be dissolved in aqueous solvent (2 capsules per 100 milliliter solvent) i.e. 4 milligram per milliliter. |
| Measure Participants | 7 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [nanogram per mililiter] |
53.0
(48.8)
|
115
(39.3)
|
| Title | Number of Participants With Dose Limiting Toxicity Adverse Events - Dose Finding Part |
|---|---|
| Description | Number of participants with Dose Limiting Toxicity adverse events for Dose finding part was reported. |
| Time Frame | During the first course (28 days) of treatment. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treated set (TS): This patient set included all patients enrolled in the trial who were documented to have taken at least one dose of study medication. |
| Arm/Group Title | Dose Finding - Level 0 | Dose Finding - Level 1 |
|---|---|---|
| Arm/Group Description | Afatinib, dose level 0. (Once daily at 80% of the recommended adult dose per m2 body surface area [BSA] using allometric scaling): Oral solid single-unit film-coated tablets for pediatric patients who are able to swallow them. Oral liquid formulation for patients who cannot swallow the film-coated tablets, or for doses which cannot be achieved by the film-coated tablets, or for pediatric patients who did not accept the film-coated tablets. Therapy with afatinib continued as long as the individual patient benefited from the therapy, did not develop secondary malignancy, and did not meet one of the criteria requiring withdrawal from treatment. Afatinib in film-coated tablet form can be given in tablets of 20, 30, 40 and 50 mg. The dose in film-coated tablets is related to the free base equivalent to afatinib. The dose of afatinib as capsule and solvent for oral solution is given as a 200 mg capsule to be dissolved in aqueous solvent (2 capsules per 100 milliliter solvent) i.e. 4 milligram per milliliter. | Afatinib, dose level 1. (Once daily at 100% of the recommended adult dose per m2 body surface area [BSA] using allometric scaling): Oral solid single-unit film-coated tablets for pediatric patients who are able to swallow them. Oral liquid formulation for patients who cannot swallow the film-coated tablets, or for doses which cannot be achieved by the film-coated tablets, or for pediatric patients who did not accept the film-coated tablets. Therapy with afatinib continued as long as the individual patient benefited from the therapy, did not develop secondary malignancy, and did not meet one of the criteria requiring withdrawal from treatment. Afatinib in film-coated tablet form can be given in tablets of 20, 30, 40 and 50 mg. The dose in film-coated tablets is related to the free base equivalent to afatinib. The dose of afatinib as capsule and solvent for oral solution is given as a 200 mg capsule to be dissolved in aqueous solvent (2 capsules per 100 milliliter solvent) i.e. 4 milligram per milliliter. |
| Measure Participants | 8 | 9 |
| Count of Participants [Participants] |
1
12.5%
|
2
22.2%
|
| Title | Number of Participants With Objective Response - Dose Finding Part |
|---|---|
| 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. |
| Time Frame | Assessed every 8 weeks until progression of disease, up to 336 days. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treated set (TS): This patient set included all patients enrolled in the trial who were documented to have taken at least one dose of study medication. |
| Arm/Group Title | Dose Finding - Level 0 | Dose Finding - Level 1 |
|---|---|---|
| Arm/Group Description | Afatinib, dose level 0. (Once daily at 80% of the recommended adult dose per m2 body surface area [BSA] using allometric scaling): Oral solid single-unit film-coated tablets for pediatric patients who are able to swallow them. Oral liquid formulation for patients who cannot swallow the film-coated tablets, or for doses which cannot be achieved by the film-coated tablets, or for pediatric patients who did not accept the film-coated tablets. Therapy with afatinib continued as long as the individual patient benefited from the therapy, did not develop secondary malignancy, and did not meet one of the criteria requiring withdrawal from treatment. Afatinib in film-coated tablet form can be given in tablets of 20, 30, 40 and 50 mg. The dose in film-coated tablets is related to the free base equivalent to afatinib. The dose of afatinib as capsule and solvent for oral solution is given as a 200 mg capsule to be dissolved in aqueous solvent (2 capsules per 100 milliliter solvent) i.e. 4 milligram per milliliter. | Afatinib, dose level 1. (Once daily at 100% of the recommended adult dose per m2 body surface area [BSA] using allometric scaling): Oral solid single-unit film-coated tablets for pediatric patients who are able to swallow them. Oral liquid formulation for patients who cannot swallow the film-coated tablets, or for doses which cannot be achieved by the film-coated tablets, or for pediatric patients who did not accept the film-coated tablets. Therapy with afatinib continued as long as the individual patient benefited from the therapy, did not develop secondary malignancy, and did not meet one of the criteria requiring withdrawal from treatment. Afatinib in film-coated tablet form can be given in tablets of 20, 30, 40 and 50 mg. The dose in film-coated tablets is related to the free base equivalent to afatinib. The dose of afatinib as capsule and solvent for oral solution is given as a 200 mg capsule to be dissolved in aqueous solvent (2 capsules per 100 milliliter solvent) i.e. 4 milligram per milliliter. |
| Measure Participants | 8 | 9 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
| Title | Progression Free Survival - Maximum Tolerated Dose (MTD) Expansion Cohort |
|---|---|
| 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. |
| Time Frame | From the first treatment until date of first progression or death, up to 336 days. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treated set (TS): This patient set included all patients enrolled in the trial who were documented to have taken at least one dose of study medication. |
| Arm/Group Title | Maximum Tolerated Dose (MTD) Expansion Cohort - Level 0 |
|---|---|
| Arm/Group Description | Afatinib, dose level 0. (Once daily at 80% of the recommended adult dose per m2 body surface area [BSA] using allometric scaling): Oral solid single-unit film-coated tablets for pediatric patients who are able to swallow them. Oral liquid formulation for patients who cannot swallow the film-coated tablets, or for doses which cannot be achieved by the film-coated tablets, or for pediatric patients who did not accept the film-coated tablets. Therapy with afatinib continued as long as the individual patient benefited from the therapy, did not develop secondary malignancy, and did not meet one of the criteria requiring withdrawal from treatment. Afatinib in film-coated tablet form can be given in tablets of 20, 30, 40 and 50 mg. The dose in film-coated tablets is related to the free base equivalent to afatinib. The dose of afatinib as capsule and solvent for oral solution is given as a 200 mg capsule to be dissolved in aqueous solvent (2 capsules per 100 milliliter solvent) i.e. 4 milligram per milliliter. |
| Measure Participants | 39 |
| Median (95% Confidence Interval) [Months] |
8.0
|
| Title | 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 |
|---|---|
| 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. |
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetics (PK) analysis set (PKS): This patient set included all patients in the TS who provided at least one PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Only participants with non-missing results were included in the analysis. |
| Arm/Group Title | Dose Finding - Level 0 | Dose Finding - Level 1 |
|---|---|---|
| Arm/Group Description | Afatinib, dose level 0. (Once daily at 80% of the recommended adult dose per m2 body surface area [BSA] using allometric scaling): Oral solid single-unit film-coated tablets for pediatric patients who are able to swallow them. Oral liquid formulation for patients who cannot swallow the film-coated tablets, or for doses which cannot be achieved by the film-coated tablets, or for pediatric patients who did not accept the film-coated tablets. Therapy with afatinib continued as long as the individual patient benefited from the therapy, did not develop secondary malignancy, and did not meet one of the criteria requiring withdrawal from treatment. Afatinib in film-coated tablet form can be given in tablets of 20, 30, 40 and 50 mg. The dose in film-coated tablets is related to the free base equivalent to afatinib. The dose of afatinib as capsule and solvent for oral solution is given as a 200 mg capsule to be dissolved in aqueous solvent (2 capsules per 100 milliliter solvent) i.e. 4 milligram per milliliter. | Afatinib, dose level 1. (Once daily at 100% of the recommended adult dose per m2 body surface area [BSA] using allometric scaling): Oral solid single-unit film-coated tablets for pediatric patients who are able to swallow them. Oral liquid formulation for patients who cannot swallow the film-coated tablets, or for doses which cannot be achieved by the film-coated tablets, or for pediatric patients who did not accept the film-coated tablets. Therapy with afatinib continued as long as the individual patient benefited from the therapy, did not develop secondary malignancy, and did not meet one of the criteria requiring withdrawal from treatment. Afatinib in film-coated tablet form can be given in tablets of 20, 30, 40 and 50 mg. The dose in film-coated tablets is related to the free base equivalent to afatinib. The dose of afatinib as capsule and solvent for oral solution is given as a 200 mg capsule to be dissolved in aqueous solvent (2 capsules per 100 milliliter solvent) i.e. 4 milligram per milliliter. |
| Measure Participants | 8 | 8 |
| Geometric Mean (Geometric Coefficient of Variation) [hours times nanogram per mililiter] |
383
(46.4)
|
512
(40.6)
|
| Title | Maximum Measured Concentration (Cmax) - Dose Finding Part/Maximum Tolerated Dose (MTD) Expansion Cohort |
|---|---|
| Description | Maximum measured concentration (Cmax) for Dose finding part/maximum tolerated dose (MTD) expansion cohort was reported. |
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetics (PK) analysis set (PKS): This patient set included all patients in the TS who provided at least one PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Only participants with non-missing results were included in the analysis. |
| Arm/Group Title | Dose Finding - Level 0 | Dose Finding - Level 1 | Maximum Tolerated Dose (MTD) Expansion Cohort - Level 0 |
|---|---|---|---|
| Arm/Group Description | Afatinib, dose level 0. (Once daily at 80% of the recommended adult dose per m2 body surface area [BSA] using allometric scaling): Oral solid single-unit film-coated tablets for pediatric patients who are able to swallow them. Oral liquid formulation for patients who cannot swallow the film-coated tablets, or for doses which cannot be achieved by the film-coated tablets, or for pediatric patients who did not accept the film-coated tablets. Therapy with afatinib continued as long as the individual patient benefited from the therapy, did not develop secondary malignancy, and did not meet one of the criteria requiring withdrawal from treatment. Afatinib in film-coated tablet form can be given in tablets of 20, 30, 40 and 50 mg. The dose in film-coated tablets is related to the free base equivalent to afatinib. The dose of afatinib as capsule and solvent for oral solution is given as a 200 mg capsule to be dissolved in aqueous solvent (2 capsules per 100 milliliter solvent) i.e. 4 milligram per milliliter. | Afatinib, dose level 1. (Once daily at 100% of the recommended adult dose per m2 body surface area [BSA] using allometric scaling): Oral solid single-unit film-coated tablets for pediatric patients who are able to swallow them. Oral liquid formulation for patients who cannot swallow the film-coated tablets, or for doses which cannot be achieved by the film-coated tablets, or for pediatric patients who did not accept the film-coated tablets. Therapy with afatinib continued as long as the individual patient benefited from the therapy, did not develop secondary malignancy, and did not meet one of the criteria requiring withdrawal from treatment. Afatinib in film-coated tablet form can be given in tablets of 20, 30, 40 and 50 mg. The dose in film-coated tablets is related to the free base equivalent to afatinib. The dose of afatinib as capsule and solvent for oral solution is given as a 200 mg capsule to be dissolved in aqueous solvent (2 capsules per 100 milliliter solvent) i.e. 4 milligram per milliliter. | Afatinib, dose level 0. (Once daily at 80% of the recommended adult dose per m2 body surface area [BSA] using allometric scaling): Oral solid single-unit film-coated tablets for pediatric patients who are able to swallow them. Oral liquid formulation for patients who cannot swallow the film-coated tablets, or for doses which cannot be achieved by the film-coated tablets, or for pediatric patients who did not accept the film-coated tablets. Therapy with afatinib continued as long as the individual patient benefited from the therapy, did not develop secondary malignancy, and did not meet one of the criteria requiring withdrawal from treatment. Afatinib in film-coated tablet form can be given in tablets of 20, 30, 40 and 50 mg. The dose in film-coated tablets is related to the free base equivalent to afatinib. The dose of afatinib as capsule and solvent for oral solution is given as a 200 mg capsule to be dissolved in aqueous solvent (2 capsules per 100 milliliter solvent) i.e. 4 milligram per milliliter. |
| Measure Participants | 8 | 8 | 36 |
| Geometric Mean (Geometric Coefficient of Variation) [nanogram per mililiter] |
36.4
(55.9)
|
43.8
(61.2)
|
30.5
(90.3)
|
| Title | Time From (Last) Dosing to the Maximum Measured Concentration (Tmax) - Dose Finding Part/Maximum Tolerated Dose (MTD) Expansion Cohort |
|---|---|
| Description | Time from (last) dosing to the maximum measured concentration (tmax) for Dose finding part/maximum tolerated dose (MTD) expansion cohort was reported. |
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetics (PK) analysis set (PKS): This patient set included all patients in the TS who provided at least one PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Only participants with non-missing results were included in the analysis. |
| Arm/Group Title | Dose Finding - Level 0 | Dose Finding - Level 1 | Maximum Tolerated Dose (MTD) Expansion Cohort - Level 0 |
|---|---|---|---|
| Arm/Group Description | Afatinib, dose level 0. (Once daily at 80% of the recommended adult dose per m2 body surface area [BSA] using allometric scaling): Oral solid single-unit film-coated tablets for pediatric patients who are able to swallow them. Oral liquid formulation for patients who cannot swallow the film-coated tablets, or for doses which cannot be achieved by the film-coated tablets, or for pediatric patients who did not accept the film-coated tablets. Therapy with afatinib continued as long as the individual patient benefited from the therapy, did not develop secondary malignancy, and did not meet one of the criteria requiring withdrawal from treatment. Afatinib in film-coated tablet form can be given in tablets of 20, 30, 40 and 50 mg. The dose in film-coated tablets is related to the free base equivalent to afatinib. The dose of afatinib as capsule and solvent for oral solution is given as a 200 mg capsule to be dissolved in aqueous solvent (2 capsules per 100 milliliter solvent) i.e. 4 milligram per milliliter. | Afatinib, dose level 1. (Once daily at 100% of the recommended adult dose per m2 body surface area [BSA] using allometric scaling): Oral solid single-unit film-coated tablets for pediatric patients who are able to swallow them. Oral liquid formulation for patients who cannot swallow the film-coated tablets, or for doses which cannot be achieved by the film-coated tablets, or for pediatric patients who did not accept the film-coated tablets. Therapy with afatinib continued as long as the individual patient benefited from the therapy, did not develop secondary malignancy, and did not meet one of the criteria requiring withdrawal from treatment. Afatinib in film-coated tablet form can be given in tablets of 20, 30, 40 and 50 mg. The dose in film-coated tablets is related to the free base equivalent to afatinib. The dose of afatinib as capsule and solvent for oral solution is given as a 200 mg capsule to be dissolved in aqueous solvent (2 capsules per 100 milliliter solvent) i.e. 4 milligram per milliliter. | Afatinib, dose level 0. (Once daily at 80% of the recommended adult dose per m2 body surface area [BSA] using allometric scaling): Oral solid single-unit film-coated tablets for pediatric patients who are able to swallow them. Oral liquid formulation for patients who cannot swallow the film-coated tablets, or for doses which cannot be achieved by the film-coated tablets, or for pediatric patients who did not accept the film-coated tablets. Therapy with afatinib continued as long as the individual patient benefited from the therapy, did not develop secondary malignancy, and did not meet one of the criteria requiring withdrawal from treatment. Afatinib in film-coated tablet form can be given in tablets of 20, 30, 40 and 50 mg. The dose in film-coated tablets is related to the free base equivalent to afatinib. The dose of afatinib as capsule and solvent for oral solution is given as a 200 mg capsule to be dissolved in aqueous solvent (2 capsules per 100 milliliter solvent) i.e. 4 milligram per milliliter. |
| Measure Participants | 8 | 8 | 36 |
| Median (Full Range) [Hours] |
3.02
|
3.43
|
3.98
|
| Title | Time From (Last) Dosing to the Maximum Measured Concentration at Steady State (Tmax,ss) - Dose Finding Part/Maximum Tolerated Dose (MTD) Expansion Cohort |
|---|---|
| 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. |
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetics (PK) analysis set (PKS): This patient set included all patients in the TS who provided at least one PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Only participants with non-missing results were included in the analysis. |
| Arm/Group Title | Dose Finding - Level 0 | Dose Finding - Level 1 | Maximum Tolerated Dose (MTD) Expansion Cohort - Level 0 |
|---|---|---|---|
| Arm/Group Description | Afatinib, dose level 0. (Once daily at 80% of the recommended adult dose per m2 body surface area [BSA] using allometric scaling): Oral solid single-unit film-coated tablets for pediatric patients who are able to swallow them. Oral liquid formulation for patients who cannot swallow the film-coated tablets, or for doses which cannot be achieved by the film-coated tablets, or for pediatric patients who did not accept the film-coated tablets. Therapy with afatinib continued as long as the individual patient benefited from the therapy, did not develop secondary malignancy, and did not meet one of the criteria requiring withdrawal from treatment. Afatinib in film-coated tablet form can be given in tablets of 20, 30, 40 and 50 mg. The dose in film-coated tablets is related to the free base equivalent to afatinib. The dose of afatinib as capsule and solvent for oral solution is given as a 200 mg capsule to be dissolved in aqueous solvent (2 capsules per 100 milliliter solvent) i.e. 4 milligram per milliliter. | Afatinib, dose level 1. (Once daily at 100% of the recommended adult dose per m2 body surface area [BSA] using allometric scaling): Oral solid single-unit film-coated tablets for pediatric patients who are able to swallow them. Oral liquid formulation for patients who cannot swallow the film-coated tablets, or for doses which cannot be achieved by the film-coated tablets, or for pediatric patients who did not accept the film-coated tablets. Therapy with afatinib continued as long as the individual patient benefited from the therapy, did not develop secondary malignancy, and did not meet one of the criteria requiring withdrawal from treatment. Afatinib in film-coated tablet form can be given in tablets of 20, 30, 40 and 50 mg. The dose in film-coated tablets is related to the free base equivalent to afatinib. The dose of afatinib as capsule and solvent for oral solution is given as a 200 mg capsule to be dissolved in aqueous solvent (2 capsules per 100 milliliter solvent) i.e. 4 milligram per milliliter. | Afatinib, dose level 0. (Once daily at 80% of the recommended adult dose per m2 body surface area [BSA] using allometric scaling): Oral solid single-unit film-coated tablets for pediatric patients who are able to swallow them. Oral liquid formulation for patients who cannot swallow the film-coated tablets, or for doses which cannot be achieved by the film-coated tablets, or for pediatric patients who did not accept the film-coated tablets. Therapy with afatinib continued as long as the individual patient benefited from the therapy, did not develop secondary malignancy, and did not meet one of the criteria requiring withdrawal from treatment. Afatinib in film-coated tablet form can be given in tablets of 20, 30, 40 and 50 mg. The dose in film-coated tablets is related to the free base equivalent to afatinib. The dose of afatinib as capsule and solvent for oral solution is given as a 200 mg capsule to be dissolved in aqueous solvent (2 capsules per 100 milliliter solvent) i.e. 4 milligram per milliliter. |
| Measure Participants | 7 | 6 | 25 |
| Median (Full Range) [Hours] |
3.00
|
2.75
|
4.17
|
| Title | Accumulation (or Effective) Half-life - Dose Finding Part/Maximum Tolerated Dose (MTD) Expansion Cohort |
|---|---|
| Description | Accumulation (or effective) half-life for Dose finding part/maximum tolerated dose (MTD) expansion cohort was reported. |
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetics (PK) analysis set (PKS): This patient set included all patients in the TS who provided at least one PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Only participants with non-missing results were included in the analysis. |
| Arm/Group Title | Dose Finding - Level 0 | Dose Finding - Level 1 | Maximum Tolerated Dose (MTD) Expansion Cohort - Level 0 |
|---|---|---|---|
| Arm/Group Description | Afatinib, dose level 0. (Once daily at 80% of the recommended adult dose per m2 body surface area [BSA] using allometric scaling): Oral solid single-unit film-coated tablets for pediatric patients who are able to swallow them. Oral liquid formulation for patients who cannot swallow the film-coated tablets, or for doses which cannot be achieved by the film-coated tablets, or for pediatric patients who did not accept the film-coated tablets. Therapy with afatinib continued as long as the individual patient benefited from the therapy, did not develop secondary malignancy, and did not meet one of the criteria requiring withdrawal from treatment. Afatinib in film-coated tablet form can be given in tablets of 20, 30, 40 and 50 mg. The dose in film-coated tablets is related to the free base equivalent to afatinib. The dose of afatinib as capsule and solvent for oral solution is given as a 200 mg capsule to be dissolved in aqueous solvent (2 capsules per 100 milliliter solvent) i.e. 4 milligram per milliliter. | Afatinib, dose level 1. (Once daily at 100% of the recommended adult dose per m2 body surface area [BSA] using allometric scaling): Oral solid single-unit film-coated tablets for pediatric patients who are able to swallow them. Oral liquid formulation for patients who cannot swallow the film-coated tablets, or for doses which cannot be achieved by the film-coated tablets, or for pediatric patients who did not accept the film-coated tablets. Therapy with afatinib continued as long as the individual patient benefited from the therapy, did not develop secondary malignancy, and did not meet one of the criteria requiring withdrawal from treatment. Afatinib in film-coated tablet form can be given in tablets of 20, 30, 40 and 50 mg. The dose in film-coated tablets is related to the free base equivalent to afatinib. The dose of afatinib as capsule and solvent for oral solution is given as a 200 mg capsule to be dissolved in aqueous solvent (2 capsules per 100 milliliter solvent) i.e. 4 milligram per milliliter. | Afatinib, dose level 0. (Once daily at 80% of the recommended adult dose per m2 body surface area [BSA] using allometric scaling): Oral solid single-unit film-coated tablets for pediatric patients who are able to swallow them. Oral liquid formulation for patients who cannot swallow the film-coated tablets, or for doses which cannot be achieved by the film-coated tablets, or for pediatric patients who did not accept the film-coated tablets. Therapy with afatinib continued as long as the individual patient benefited from the therapy, did not develop secondary malignancy, and did not meet one of the criteria requiring withdrawal from treatment. Afatinib in film-coated tablet form can be given in tablets of 20, 30, 40 and 50 mg. The dose in film-coated tablets is related to the free base equivalent to afatinib. The dose of afatinib as capsule and solvent for oral solution is given as a 200 mg capsule to be dissolved in aqueous solvent (2 capsules per 100 milliliter solvent) i.e. 4 milligram per milliliter. |
| Measure Participants | 7 | 6 | 24 |
| Geometric Mean (Geometric Coefficient of Variation) [hours] |
18.7
(44.3)
|
31.0
(56.7)
|
30.3
(83.6)
|
| Title | Duration of Objective Response - Maximum Tolerated Dose (MTD) Expansion Cohort |
|---|---|
| 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. |
| Time Frame | From first documented response until the earliest of disease progression or death, up to 336 days. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Treated set (TS): This patient set included all patients enrolled in the trial who were documented to have taken at least one dose of study medication. |
| Arm/Group Title | Maximum Tolerated Dose (MTD) Expansion Cohort - Level 0 |
|---|---|
| Arm/Group Description | Afatinib, dose level 0. (Once daily at 80% of the recommended adult dose per m2 body surface area [BSA] using allometric scaling): Oral solid single-unit film-coated tablets for pediatric patients who are able to swallow them. Oral liquid formulation for patients who cannot swallow the film-coated tablets, or for doses which cannot be achieved by the film-coated tablets, or for pediatric patients who did not accept the film-coated tablets. Therapy with afatinib continued as long as the individual patient benefited from the therapy, did not develop secondary malignancy, and did not meet one of the criteria requiring withdrawal from treatment. Afatinib in film-coated tablet form can be given in tablets of 20, 30, 40 and 50 mg. The dose in film-coated tablets is related to the free base equivalent to afatinib. The dose of afatinib as capsule and solvent for oral solution is given as a 200 mg capsule to be dissolved in aqueous solvent (2 capsules per 100 milliliter solvent) i.e. 4 milligram per milliliter. |
| Measure Participants | 39 |
| Median (Full Range) [Days] |
62
|
| Title | Area Under the Curve Over Dosing Interval τ at Steady State (AUCτ,ss) - Maximum Tolerated Dose (MTD) Expansion Cohort |
|---|---|
| Description | Area under the curve over dosing interval τ at steady state (AUCτ,ss) in maximum tolerated dose (MTD) expansion cohort was reported. |
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetics (PK) analysis set (PKS): This patient set included all patients in the TS who provided at least one PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Only participants with non-missing results were included in the analysis. |
| Arm/Group Title | Maximum Tolerated Dose (MTD) Expansion Cohort - Level 0 |
|---|---|
| Arm/Group Description | Afatinib, dose level 0. (Once daily at 80% of the recommended adult dose per m2 body surface area [BSA] using allometric scaling): Oral solid single-unit film-coated tablets for pediatric patients who are able to swallow them. Oral liquid formulation for patients who cannot swallow the film-coated tablets, or for doses which cannot be achieved by the film-coated tablets, or for pediatric patients who did not accept the film-coated tablets. Therapy with afatinib continued as long as the individual patient benefited from the therapy, did not develop secondary malignancy, and did not meet one of the criteria requiring withdrawal from treatment. Afatinib in film-coated tablet form can be given in tablets of 20, 30, 40 and 50 mg. The dose in film-coated tablets is related to the free base equivalent to afatinib. The dose of afatinib as capsule and solvent for oral solution is given as a 200 mg capsule to be dissolved in aqueous solvent (2 capsules per 100 milliliter solvent) i.e. 4 milligram per milliliter. |
| Measure Participants | 25 |
| Geometric Mean (Geometric Coefficient of Variation) [hours times nanogram per milliliter] |
780
(60.7)
|
| Title | Maximum Measured Concentration of the Analyte in Plasma at Steady State (Cmax,ss) - Maximum Tolerated Dose (MTD) Expansion Cohort |
|---|---|
| Description | Maximum measured concentration of the analyte in plasma at steady state (Cmax,ss) in maximum tolerated dose (MTD) expansion cohort was reported. |
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetics (PK) analysis set (PKS): This patient set included all patients in the TS who provided at least one PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Only participants with non-missing results were included in the analysis. |
| Arm/Group Title | Maximum Tolerated Dose (MTD) Expansion Cohort - Level 0 |
|---|---|
| Arm/Group Description | Afatinib, dose level 0. (Once daily at 80% of the recommended adult dose per m2 body surface area [BSA] using allometric scaling): Oral solid single-unit film-coated tablets for pediatric patients who are able to swallow them. Oral liquid formulation for patients who cannot swallow the film-coated tablets, or for doses which cannot be achieved by the film-coated tablets, or for pediatric patients who did not accept the film-coated tablets. Therapy with afatinib continued as long as the individual patient benefited from the therapy, did not develop secondary malignancy, and did not meet one of the criteria requiring withdrawal from treatment. Afatinib in film-coated tablet form can be given in tablets of 20, 30, 40 and 50 mg. The dose in film-coated tablets is related to the free base equivalent to afatinib. The dose of afatinib as capsule and solvent for oral solution is given as a 200 mg capsule to be dissolved in aqueous solvent (2 capsules per 100 milliliter solvent) i.e. 4 milligram per milliliter. |
| Measure Participants | 25 |
| Geometric Mean (Geometric Coefficient of Variation) [nanogram per mililiter] |
52.5
(61.0)
|
Adverse Events
| Time Frame | From the first drug administration until end of study, up to 336 days. | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Treated set (TS) This patient set included all patients enrolled in the trial who were documented to have taken at least one dose of study medication. | |||||
| Arm/Group Title | Dose Finding - Level 0 | Dose Finding - Level 1 | Maximum Tolerated Dose (MTD) Expansion Cohort - Level 0 | |||
| Arm/Group Description | Afatinib, dose level 0. (Once daily at 80% of the recommended adult dose per m2 body surface area [BSA] using allometric scaling): Oral solid single-unit film-coated tablets for pediatric patients who are able to swallow them. Oral liquid formulation for patients who cannot swallow the film-coated tablets, or for doses which cannot be achieved by the film-coated tablets, or for pediatric patients who did not accept the film-coated tablets. Therapy with afatinib continued as long as the individual patient benefited from the therapy, did not develop secondary malignancy, and did not meet one of the criteria requiring withdrawal from treatment. Afatinib in film-coated tablet form can be given in tablets of 20, 30, 40 and 50 mg. The dose in film-coated tablets is related to the free base equivalent to afatinib. The dose of afatinib as capsule and solvent for oral solution is given as a 200 mg capsule to be dissolved in aqueous solvent (2 capsules per 100 milliliter solvent) i.e. 4 milligram per milliliter. | Afatinib, dose level 1. (Once daily at 100% of the recommended adult dose per m2 body surface area [BSA] using allometric scaling): Oral solid single-unit film-coated tablets for pediatric patients who are able to swallow them. Oral liquid formulation for patients who cannot swallow the film-coated tablets, or for doses which cannot be achieved by the film-coated tablets, or for pediatric patients who did not accept the film-coated tablets. Therapy with afatinib continued as long as the individual patient benefited from the therapy, did not develop secondary malignancy, and did not meet one of the criteria requiring withdrawal from treatment. Afatinib in film-coated tablet form can be given in tablets of 20, 30, 40 and 50 mg. The dose in film-coated tablets is related to the free base equivalent to afatinib. The dose of afatinib as capsule and solvent for oral solution is given as a 200 mg capsule to be dissolved in aqueous solvent (2 capsules per 100 milliliter solvent) i.e. 4 milligram per milliliter. | Afatinib, dose level 0. (Once daily at 80% of the recommended adult dose per m2 body surface area [BSA] using allometric scaling): Oral solid single-unit film-coated tablets for pediatric patients who are able to swallow them. Oral liquid formulation for patients who cannot swallow the film-coated tablets, or for doses which cannot be achieved by the film-coated tablets, or for pediatric patients who did not accept the film-coated tablets. Therapy with afatinib continued as long as the individual patient benefited from the therapy, did not develop secondary malignancy, and did not meet one of the criteria requiring withdrawal from treatment. Afatinib in film-coated tablet form can be given in tablets of 20, 30, 40 and 50 mg. The dose in film-coated tablets is related to the free base equivalent to afatinib. The dose of afatinib as capsule and solvent for oral solution is given as a 200 mg capsule to be dissolved in aqueous solvent (2 capsules per 100 milliliter solvent) i.e. 4 milligram per milliliter. | |||
All Cause Mortality |
||||||
| Dose Finding - Level 0 | Dose Finding - Level 1 | Maximum Tolerated Dose (MTD) Expansion Cohort - Level 0 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 8/8 (100%) | 9/9 (100%) | 29/39 (74.4%) | |||
Serious Adverse Events |
||||||
| Dose Finding - Level 0 | Dose Finding - Level 1 | Maximum Tolerated Dose (MTD) Expansion Cohort - Level 0 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 7/8 (87.5%) | 6/9 (66.7%) | 20/39 (51.3%) | |||
| Blood and lymphatic system disorders | ||||||
| Lymphopenia | 0/8 (0%) | 0/9 (0%) | 1/39 (2.6%) | |||
| Eye disorders | ||||||
| Blindness | 1/8 (12.5%) | 0/9 (0%) | 0/39 (0%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal pain | 1/8 (12.5%) | 0/9 (0%) | 0/39 (0%) | |||
| Ascites | 0/8 (0%) | 0/9 (0%) | 1/39 (2.6%) | |||
| Diarrhoea | 0/8 (0%) | 3/9 (33.3%) | 0/39 (0%) | |||
| Stomatitis | 0/8 (0%) | 0/9 (0%) | 2/39 (5.1%) | |||
| Vomiting | 3/8 (37.5%) | 2/9 (22.2%) | 2/39 (5.1%) | |||
| General disorders | ||||||
| General physical health deterioration | 1/8 (12.5%) | 0/9 (0%) | 0/39 (0%) | |||
| Pyrexia | 1/8 (12.5%) | 1/9 (11.1%) | 2/39 (5.1%) | |||
| Infections and infestations | ||||||
| Gastroenteritis viral | 1/8 (12.5%) | 0/9 (0%) | 1/39 (2.6%) | |||
| Paronychia | 0/8 (0%) | 0/9 (0%) | 1/39 (2.6%) | |||
| Upper respiratory tract infection | 0/8 (0%) | 0/9 (0%) | 1/39 (2.6%) | |||
| Viral infection | 0/8 (0%) | 0/9 (0%) | 1/39 (2.6%) | |||
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 0/8 (0%) | 2/9 (22.2%) | 0/39 (0%) | |||
| Dehydration | 0/8 (0%) | 1/9 (11.1%) | 0/39 (0%) | |||
| Hypernatraemia | 0/8 (0%) | 1/9 (11.1%) | 0/39 (0%) | |||
| Hypoglycaemia | 0/8 (0%) | 0/9 (0%) | 1/39 (2.6%) | |||
| Hypokalaemia | 0/8 (0%) | 1/9 (11.1%) | 0/39 (0%) | |||
| Hyponatraemia | 0/8 (0%) | 0/9 (0%) | 1/39 (2.6%) | |||
| Nervous system disorders | ||||||
| Altered state of consciousness | 0/8 (0%) | 0/9 (0%) | 1/39 (2.6%) | |||
| Aphasia | 0/8 (0%) | 0/9 (0%) | 1/39 (2.6%) | |||
| Encephalopathy | 0/8 (0%) | 0/9 (0%) | 1/39 (2.6%) | |||
| Generalised tonic-clonic seizure | 0/8 (0%) | 0/9 (0%) | 1/39 (2.6%) | |||
| Haemorrhage intracranial | 0/8 (0%) | 0/9 (0%) | 1/39 (2.6%) | |||
| Headache | 3/8 (37.5%) | 1/9 (11.1%) | 0/39 (0%) | |||
| Hemiparesis | 1/8 (12.5%) | 0/9 (0%) | 1/39 (2.6%) | |||
| Hydrocephalus | 0/8 (0%) | 0/9 (0%) | 2/39 (5.1%) | |||
| Intracranial pressure increased | 0/8 (0%) | 0/9 (0%) | 1/39 (2.6%) | |||
| Somnolence | 1/8 (12.5%) | 0/9 (0%) | 0/39 (0%) | |||
| Status epilepticus | 0/8 (0%) | 1/9 (11.1%) | 0/39 (0%) | |||
| Psychiatric disorders | ||||||
| Anxiety | 0/8 (0%) | 0/9 (0%) | 1/39 (2.6%) | |||
| Renal and urinary disorders | ||||||
| Urinary tract disorder | 0/8 (0%) | 0/9 (0%) | 1/39 (2.6%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Dyspnoea | 0/8 (0%) | 1/9 (11.1%) | 1/39 (2.6%) | |||
| Hypoxia | 0/8 (0%) | 0/9 (0%) | 2/39 (5.1%) | |||
| Oropharyngeal pain | 0/8 (0%) | 1/9 (11.1%) | 0/39 (0%) | |||
| Pleural effusion | 0/8 (0%) | 0/9 (0%) | 1/39 (2.6%) | |||
| Respiratory arrest | 0/8 (0%) | 0/9 (0%) | 1/39 (2.6%) | |||
| Respiratory distress | 0/8 (0%) | 0/9 (0%) | 1/39 (2.6%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Dermatitis acneiform | 0/8 (0%) | 0/9 (0%) | 1/39 (2.6%) | |||
| Skin ulcer | 0/8 (0%) | 0/9 (0%) | 1/39 (2.6%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Dose Finding - Level 0 | Dose Finding - Level 1 | Maximum Tolerated Dose (MTD) Expansion Cohort - Level 0 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 8/8 (100%) | 9/9 (100%) | 38/39 (97.4%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 3/8 (37.5%) | 1/9 (11.1%) | 7/39 (17.9%) | |||
| Leukopenia | 1/8 (12.5%) | 0/9 (0%) | 0/39 (0%) | |||
| Lymphopenia | 0/8 (0%) | 1/9 (11.1%) | 2/39 (5.1%) | |||
| Neutropenia | 1/8 (12.5%) | 0/9 (0%) | 0/39 (0%) | |||
| Cardiac disorders | ||||||
| Sinus bradycardia | 0/8 (0%) | 0/9 (0%) | 2/39 (5.1%) | |||
| Sinus tachycardia | 0/8 (0%) | 0/9 (0%) | 2/39 (5.1%) | |||
| Eye disorders | ||||||
| Dry eye | 3/8 (37.5%) | 0/9 (0%) | 3/39 (7.7%) | |||
| Eye discharge | 0/8 (0%) | 1/9 (11.1%) | 0/39 (0%) | |||
| Eye pruritus | 1/8 (12.5%) | 0/9 (0%) | 1/39 (2.6%) | |||
| Keratitis | 0/8 (0%) | 1/9 (11.1%) | 0/39 (0%) | |||
| Punctate keratitis | 1/8 (12.5%) | 0/9 (0%) | 0/39 (0%) | |||
| Vision blurred | 1/8 (12.5%) | 0/9 (0%) | 0/39 (0%) | |||
| Visual acuity reduced | 1/8 (12.5%) | 0/9 (0%) | 0/39 (0%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal pain | 4/8 (50%) | 2/9 (22.2%) | 8/39 (20.5%) | |||
| Abdominal pain upper | 1/8 (12.5%) | 0/9 (0%) | 1/39 (2.6%) | |||
| Anal haemorrhage | 1/8 (12.5%) | 0/9 (0%) | 0/39 (0%) | |||
| Angular cheilitis | 1/8 (12.5%) | 0/9 (0%) | 1/39 (2.6%) | |||
| Cheilitis | 2/8 (25%) | 2/9 (22.2%) | 6/39 (15.4%) | |||
| Constipation | 6/8 (75%) | 1/9 (11.1%) | 4/39 (10.3%) | |||
| Diarrhoea | 6/8 (75%) | 6/9 (66.7%) | 30/39 (76.9%) | |||
| Dyschezia | 1/8 (12.5%) | 0/9 (0%) | 0/39 (0%) | |||
| Dysphagia | 1/8 (12.5%) | 1/9 (11.1%) | 0/39 (0%) | |||
| Glossitis | 1/8 (12.5%) | 0/9 (0%) | 1/39 (2.6%) | |||
| Lip dry | 0/8 (0%) | 0/9 (0%) | 5/39 (12.8%) | |||
| Mouth ulceration | 1/8 (12.5%) | 0/9 (0%) | 1/39 (2.6%) | |||
| Nausea | 1/8 (12.5%) | 2/9 (22.2%) | 15/39 (38.5%) | |||
| Oral pain | 0/8 (0%) | 0/9 (0%) | 3/39 (7.7%) | |||
| Stomatitis | 3/8 (37.5%) | 1/9 (11.1%) | 9/39 (23.1%) | |||
| Tongue eruption | 1/8 (12.5%) | 0/9 (0%) | 0/39 (0%) | |||
| Vomiting | 3/8 (37.5%) | 6/9 (66.7%) | 16/39 (41%) | |||
| General disorders | ||||||
| Asthenia | 1/8 (12.5%) | 0/9 (0%) | 2/39 (5.1%) | |||
| Disease progression | 1/8 (12.5%) | 0/9 (0%) | 0/39 (0%) | |||
| Fatigue | 4/8 (50%) | 1/9 (11.1%) | 10/39 (25.6%) | |||
| Mucosal inflammation | 0/8 (0%) | 1/9 (11.1%) | 7/39 (17.9%) | |||
| Pain | 1/8 (12.5%) | 0/9 (0%) | 1/39 (2.6%) | |||
| Pyrexia | 1/8 (12.5%) | 2/9 (22.2%) | 5/39 (12.8%) | |||
| Xerosis | 0/8 (0%) | 1/9 (11.1%) | 2/39 (5.1%) | |||
| Infections and infestations | ||||||
| Conjunctivitis | 1/8 (12.5%) | 0/9 (0%) | 3/39 (7.7%) | |||
| Cystitis | 1/8 (12.5%) | 0/9 (0%) | 0/39 (0%) | |||
| Ear infection | 0/8 (0%) | 1/9 (11.1%) | 0/39 (0%) | |||
| Escherichia infection | 1/8 (12.5%) | 0/9 (0%) | 0/39 (0%) | |||
| Herpes zoster | 0/8 (0%) | 1/9 (11.1%) | 0/39 (0%) | |||
| Impetigo | 1/8 (12.5%) | 0/9 (0%) | 1/39 (2.6%) | |||
| Infection | 1/8 (12.5%) | 0/9 (0%) | 1/39 (2.6%) | |||
| Nasopharyngitis | 0/8 (0%) | 1/9 (11.1%) | 2/39 (5.1%) | |||
| Paronychia | 1/8 (12.5%) | 0/9 (0%) | 9/39 (23.1%) | |||
| Pharyngitis | 0/8 (0%) | 1/9 (11.1%) | 0/39 (0%) | |||
| Rhinitis | 0/8 (0%) | 0/9 (0%) | 2/39 (5.1%) | |||
| Tinea capitis | 1/8 (12.5%) | 0/9 (0%) | 0/39 (0%) | |||
| Upper respiratory tract infection | 1/8 (12.5%) | 0/9 (0%) | 1/39 (2.6%) | |||
| Urinary tract infection | 1/8 (12.5%) | 0/9 (0%) | 1/39 (2.6%) | |||
| Viral infection | 0/8 (0%) | 1/9 (11.1%) | 1/39 (2.6%) | |||
| Injury, poisoning and procedural complications | ||||||
| Fall | 0/8 (0%) | 1/9 (11.1%) | 1/39 (2.6%) | |||
| Upper limb fracture | 0/8 (0%) | 1/9 (11.1%) | 0/39 (0%) | |||
| Investigations | ||||||
| Alanine aminotransferase increased | 2/8 (25%) | 1/9 (11.1%) | 5/39 (12.8%) | |||
| Aspartate aminotransferase increased | 0/8 (0%) | 1/9 (11.1%) | 3/39 (7.7%) | |||
| Blood creatinine increased | 0/8 (0%) | 1/9 (11.1%) | 1/39 (2.6%) | |||
| Blood lactate dehydrogenase increased | 1/8 (12.5%) | 0/9 (0%) | 2/39 (5.1%) | |||
| Blood thyroid stimulating hormone increased | 1/8 (12.5%) | 0/9 (0%) | 0/39 (0%) | |||
| Blood uric acid increased | 0/8 (0%) | 0/9 (0%) | 2/39 (5.1%) | |||
| C-reactive protein increased | 0/8 (0%) | 0/9 (0%) | 2/39 (5.1%) | |||
| Gamma-glutamyltransferase increased | 1/8 (12.5%) | 1/9 (11.1%) | 2/39 (5.1%) | |||
| Lymphocyte count decreased | 0/8 (0%) | 3/9 (33.3%) | 4/39 (10.3%) | |||
| Neutrophil count decreased | 1/8 (12.5%) | 0/9 (0%) | 2/39 (5.1%) | |||
| Platelet count decreased | 1/8 (12.5%) | 0/9 (0%) | 1/39 (2.6%) | |||
| Weight decreased | 1/8 (12.5%) | 3/9 (33.3%) | 10/39 (25.6%) | |||
| White blood cell count decreased | 0/8 (0%) | 1/9 (11.1%) | 3/39 (7.7%) | |||
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 3/8 (37.5%) | 1/9 (11.1%) | 7/39 (17.9%) | |||
| Dehydration | 0/8 (0%) | 2/9 (22.2%) | 1/39 (2.6%) | |||
| Hyperglycaemia | 1/8 (12.5%) | 1/9 (11.1%) | 2/39 (5.1%) | |||
| Hyperkalaemia | 1/8 (12.5%) | 0/9 (0%) | 1/39 (2.6%) | |||
| Hypermagnesaemia | 1/8 (12.5%) | 0/9 (0%) | 0/39 (0%) | |||
| Hypernatraemia | 1/8 (12.5%) | 1/9 (11.1%) | 0/39 (0%) | |||
| Hypoalbuminaemia | 1/8 (12.5%) | 1/9 (11.1%) | 0/39 (0%) | |||
| Hypocalcaemia | 0/8 (0%) | 1/9 (11.1%) | 1/39 (2.6%) | |||
| Hypoglycaemia | 2/8 (25%) | 0/9 (0%) | 0/39 (0%) | |||
| Hypokalaemia | 0/8 (0%) | 1/9 (11.1%) | 3/39 (7.7%) | |||
| Hypomagnesaemia | 0/8 (0%) | 1/9 (11.1%) | 0/39 (0%) | |||
| Hyponatraemia | 0/8 (0%) | 1/9 (11.1%) | 4/39 (10.3%) | |||
| Hypophosphataemia | 1/8 (12.5%) | 1/9 (11.1%) | 3/39 (7.7%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Groin pain | 0/8 (0%) | 0/9 (0%) | 2/39 (5.1%) | |||
| Muscle spasms | 0/8 (0%) | 0/9 (0%) | 2/39 (5.1%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Tumour pain | 1/8 (12.5%) | 0/9 (0%) | 0/39 (0%) | |||
| Nervous system disorders | ||||||
| Aphasia | 1/8 (12.5%) | 0/9 (0%) | 0/39 (0%) | |||
| Ataxia | 0/8 (0%) | 0/9 (0%) | 2/39 (5.1%) | |||
| Dizziness | 0/8 (0%) | 0/9 (0%) | 2/39 (5.1%) | |||
| Dysarthria | 0/8 (0%) | 0/9 (0%) | 2/39 (5.1%) | |||
| Headache | 3/8 (37.5%) | 3/9 (33.3%) | 9/39 (23.1%) | |||
| Lethargy | 0/8 (0%) | 0/9 (0%) | 2/39 (5.1%) | |||
| Neurological decompensation | 1/8 (12.5%) | 0/9 (0%) | 0/39 (0%) | |||
| Peripheral motor neuropathy | 1/8 (12.5%) | 0/9 (0%) | 0/39 (0%) | |||
| Somnolence | 1/8 (12.5%) | 0/9 (0%) | 0/39 (0%) | |||
| VIth nerve disorder | 1/8 (12.5%) | 0/9 (0%) | 0/39 (0%) | |||
| Psychiatric disorders | ||||||
| Anxiety | 0/8 (0%) | 1/9 (11.1%) | 1/39 (2.6%) | |||
| Insomnia | 1/8 (12.5%) | 0/9 (0%) | 0/39 (0%) | |||
| Renal and urinary disorders | ||||||
| Proteinuria | 1/8 (12.5%) | 0/9 (0%) | 1/39 (2.6%) | |||
| Urinary retention | 1/8 (12.5%) | 0/9 (0%) | 0/39 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Asthma | 0/8 (0%) | 1/9 (11.1%) | 0/39 (0%) | |||
| Cough | 2/8 (25%) | 0/9 (0%) | 5/39 (12.8%) | |||
| Epistaxis | 4/8 (50%) | 1/9 (11.1%) | 7/39 (17.9%) | |||
| Hypoxia | 1/8 (12.5%) | 0/9 (0%) | 0/39 (0%) | |||
| Nasal congestion | 1/8 (12.5%) | 0/9 (0%) | 0/39 (0%) | |||
| Nasal oedema | 0/8 (0%) | 1/9 (11.1%) | 0/39 (0%) | |||
| Nasal pruritus | 0/8 (0%) | 1/9 (11.1%) | 0/39 (0%) | |||
| Oropharyngeal pain | 0/8 (0%) | 0/9 (0%) | 2/39 (5.1%) | |||
| Pharyngeal inflammation | 1/8 (12.5%) | 0/9 (0%) | 1/39 (2.6%) | |||
| Tachypnoea | 1/8 (12.5%) | 0/9 (0%) | 0/39 (0%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Alopecia | 1/8 (12.5%) | 0/9 (0%) | 0/39 (0%) | |||
| Dermatitis | 0/8 (0%) | 1/9 (11.1%) | 1/39 (2.6%) | |||
| Dermatitis acneiform | 1/8 (12.5%) | 1/9 (11.1%) | 9/39 (23.1%) | |||
| Dermatitis diaper | 0/8 (0%) | 1/9 (11.1%) | 0/39 (0%) | |||
| Dry skin | 2/8 (25%) | 4/9 (44.4%) | 10/39 (25.6%) | |||
| Eczema | 1/8 (12.5%) | 0/9 (0%) | 1/39 (2.6%) | |||
| Erythema | 0/8 (0%) | 2/9 (22.2%) | 2/39 (5.1%) | |||
| Hair colour changes | 1/8 (12.5%) | 0/9 (0%) | 0/39 (0%) | |||
| Hand dermatitis | 0/8 (0%) | 1/9 (11.1%) | 0/39 (0%) | |||
| Hyperhidrosis | 1/8 (12.5%) | 0/9 (0%) | 0/39 (0%) | |||
| Pruritus | 2/8 (25%) | 0/9 (0%) | 3/39 (7.7%) | |||
| Rash | 1/8 (12.5%) | 1/9 (11.1%) | 4/39 (10.3%) | |||
| Rash maculo-papular | 0/8 (0%) | 1/9 (11.1%) | 4/39 (10.3%) | |||
| Rash papular | 0/8 (0%) | 0/9 (0%) | 2/39 (5.1%) | |||
| Skin fissures | 1/8 (12.5%) | 1/9 (11.1%) | 0/39 (0%) | |||
| Skin irritation | 0/8 (0%) | 1/9 (11.1%) | 0/39 (0%) | |||
| Vascular disorders | ||||||
| Hypertension | 0/8 (0%) | 0/9 (0%) | 3/39 (7.7%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Boehringer Ingelheim, Call Center |
|---|---|
| Organization | Boehringer Ingelheim |
| Phone | 1-800-243-0127 |
| clintriage.rdg@boehringer-ingelheim.com |
Responsible Party:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT02372006
Other Study ID Numbers:
- 1200.120
- 2014-002123-10
First Posted:
Feb 26, 2015
Last Update Posted:
Mar 4, 2021
Last Verified:
Mar 1, 2021