Glioblastoma
Conditions
Brief summary
This study is a phase I, open label trial to determine the Maximum Tolerated Dose (MTD), safety, pharmacokinetics, and efficacy of BIBW 2992 (an epidermal growth factor receptor(EGFR)inhibitor) to be used in combination with: * radiotherapy alone (in patients with an unmethylated (functioning) MGMT gene regulator) or * radiotherapy and Temozolomide (in patients with a methylated (silenced) O6-methylguanine-DNA methyltransferase gene (MGMT) to treat newly diagnosed patients with Grade IV Glioblastoma (primary brain cancer).
Interventions
DRUGTemozolomide
During RT: 75 mg/m2 daily , 4 weeks after RT: given days 1 to 5 of 28 day cycles (150 mg/m2 in cycle 1, 200 mg/m2 in cycle 2 up to cycle 6)
PROCEDURERadiotherapy
Day 1 to day 42
DRUGBIBW2992
Escalating dose cohorts during Radiotherapy(RT) period, fixed dose after RT
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 69 Years
Healthy volunteers
No
Inclusion criteria
1. Histologically-confirmed WHO Grade IV newly diagnosed malignant glioma. 2. Proven MGMT gene promoter methylation status 3. Available early postoperative Gd-enhanced MRI (within 72 hours after initial surgery). In case a patient did not perform a Gd-enhanced MRI within 72 hours post surgery, a Gd-MRI is to be performed prior to start of study treatment. 4. Age more or equal to 18 years and less than 70 years at entry 5. Karnofsky Performance Scale (KPS) more or equal to 70% 6. Patients receiving corticosteroids have to receive a stable or decreasing dose for at least 14 days before start of treatment. 7. Written informed consent that is consistent with local law and ICH- Good Clinical Practice (GCP) guidelines.
Exclusion criteria
1. Less than two weeks from surgical resection or other major surgical procedure at start of treatment. 2. Planned surgery for other diseases 3. Placement of Gliadel® wafer at surgery. 4. Prior or planned radiotherapy of the cranium including brachytherapy and/or radiosurgery for GBM. 5. Treatment with other investigational drugs; participation in another clinical study including exposure to the investigational product within the past 4 weeks before start of therapy or concomitantly with this study. 6. Active infectious disease requiring intravenous therapy. 7. Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C. 8. Gastrointestinal disorders that may interfere with the absorption of the study drug or chronic diarrhoea. 9. Patients with known pre-existing interstitial lung disease 10. Serious illness or concomitant non-oncological disease considered by the investigator to be incompatible with the protocol. 11. Patient is less than 3 years free of another primary malignancy except: if the other primary malignancy is either not currently clinically significant or does not require active intervention (such as a basal cell skin cancer or a cervical carcinoma in situ). Existence of any other malignant disease is not allowed. 12. Cardiac left ventricular function with resting ejection fraction less than 50%. 13. Absolute neutrophil count (ANC) less than 1500/mm3. 14. Platelet count less than 100,000/mm3. 15. Bilirubin greater than 1.5 x upper limit of institutional norm. 16. Aspartate amino transferase (AST) greater than 3 x upper limit of institutional norm. 17. Serum creatinine greater than 1.5 x upper limit of institutional norm. 18. Patients who are sexually active and unwilling to use a medically acceptable method of contraception. 19. Pregnancy or breast-feeding. 20. Patients unable to comply with the protocol. 21. Known or suspected active drug or alcohol abuse. 22. Known hypersensitivity to BIBW 2992 or the excipients of any of the trial drugs.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Investigator Defined Dose Limiting Toxicities (DLT) During the RT Phase | 6 weeks | Adverse event (AE) related to afatinib with any one criteria; Hematological: Common terminology criteria for adverse events (CTCAE) Grade 4 neutropenia (Absolute neutrophil count, including bands \<500/cubic millimeter (mm³)) for \>7 days, CTCAE Grade 3 or 4 neutropenia of any duration associated with fever \>38.3 Celsius, CTCAE Grade 3 thrombocytopenia (platelet count \<50000 - 25000/mm³), All other toxicities of CTCAE Grade ≥3 leading interruption of treatment \> 14 days. Non-hematological: CTCAE Grade ≥3 nausea or vomiting despite appropriate use of standard anti-emetics for ≥3 days, CTCAE Grade ≥3 diarrhea despite appropriate use of standard anti-diarrheal therapy for ≥3 days, CTCAE Grade ≥3 rash despite standard medical management and lasting \>7 days, CTCAE Grade ≥2 cardiac left ventricular function, CTCAE Grade ≥2 worsening of renal function as measured by serum creatinine, newly developed proteinuria or decrease in glomerular filtration rate, All other toxicities of CTCAE Grade ≥3. |
| Maximum Tolerated Dose (MTD) of Afatinib | 6 weeks | The MTD was defined as the highest afatinib dose level, at which no more than 1 out of 6 patients experienced drug-related DLT, i.e. the highest afatinib dose with a DLT incidence ≤17%. A separate MTD was determined for afatinib and RT (Regimen U), and for afatinib, TMZ, and RT (Regimen M). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and Intensity of Adverse Events (AE) According to Common Terminology Criteria of Adverse Events (CTCAE v.3.0) | From the first administration of trial medication until 4 weeks after the last administration of trial medication, up to approximately 338 weeks | Incidence and intensity of adverse events (AE) according to Common Terminology Criteria of Adverse Events (CTCAE v.3.0). The CTCAE grades are: 1 (mild AE), 2 (moderate AE), 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related to AE). |
| The Objective Tumour Response According to the Macdonald Criteria | From the first administration of trial medication until 4 weeks after the last administration of trial medication, up to approximately 338 weeks | Objective response was defined as a best overall response of complete response (CR) or partial response (PR). The best overall response was the best overall response to trial medication according to the Macdonald criteria recorded since the first administration of trial medication and until the earliest of disease progression, death, or start of further anti-cancer treatment. Tumour response was assessed based on local radiological image evaluation by the investigators according to the Macdonald criteria: Complete Response (CR): Disappearance of all enhancing tumour on consecutive Magnetic resonance imaging (MRI) scans at least 28 days apart, off steroids, and neurologically stable or improved. Partial Response (PR): At least 50% reduction in size of enhancing tumour on consecutive MRI scans at least 28 days apart, steroids stable or reduced, and neurologically stable or improved. |
| Concentration of Afatinib in Plasma at Steady State Pre-dose on Days 8, 15 and 29 | Pharmacokinetic blood sample were taken at 5 minutes before drug on days 8, 15 and 29 and 1, 3 and 6 hours after drug administration on day 15 | Concentration of afatinib in plasma at steady state pre-dose (Cpre,ss) on days 8, 15 and 29. |
Countries
United Kingdom
Participant flow
Recruitment details
This is phase I, open-label, non-randomised, uncontrolled dose-escalation trial using a rule-based 3+3 design and patient stratification to explore safety of combining afatinib and radiotherapy with or without temozolomide in newly diagnosed Glioblastoma multiforme (GBM)
Pre-assignment details
All patients were screened for eligibility to participate in the trial. Patients attended a specialist sites which ensured that they met all strictly implemented inclusion/exclusion criteria. Patients were not to be entered to trial if any one of the specific entry criteria was violated.
Participants by arm
| Arm | Count |
|---|---|
| Afatinib 20 Milligram, Radiotherapy + Temozolomide - Regimen M Patients were administered Afatinib 20 milligram (mg) film-coated tablet once daily orally plus radiotherapy (RT) i.e. focal radiation at a dose of 2 Gray per fraction on 5 days per week for 6 weeks (RT phase) (total dose of 60 Gray (Gy)) plus Temozolomide (TMZ) 75 milligrams per square meter (mg/m2) capsules continuous daily oral dosing. In the maintenance phase after RT, patients stopped TMZ for 4 weeks and restarted TMZ at 150 mg/m2 in cycle 1 and 200 mg/m2 in cycles 2 to 6 on days 1 to 5 of 28-day treatment cycles. Patients were administered Afatinib 40 milligram (mg) film-coated tablet once daily after RT. Dose reductions of Afatinib were allowed if 40 mg or 30 mg were not tolerated. The treatment duration was until tumour progression or occurrence of undue adverse reactions, whichever occurred first. | 7 |
| Afatinib 30 mg, Radiotherapy + Temozolomide - Regimen M Patients were administered Afatinib 30 mg film-coated tablet once daily orally plus radiotherapy (RT) i.e. focal radiation at a dose of 2 Gray per fraction on 5 days per week for 6 weeks (RT phase) (total dose of 60 Gray) plus Temozolomide 75 milligrams per square meter (mg/m2) capsules continuous daily oral dosing. In the maintenance phase after RT, patients stopped TMZ for 4 weeks and restarted TMZ at 150 mg/m2 in cycle 1 and 200 mg/m2 in cycles 2 to 6 on days 1 to 5 of 28-day treatment cycles. Patients were administered Afatinib 40 milligram (mg) film-coated tablet once daily after RT. Dose reductions of Afatinib were allowed if 40 mg or 30 mg were not tolerated. The treatment duration was until tumour progression or occurrence of undue adverse reactions, whichever occurred first. | 6 |
| Afatinib 40 mg, Radiotherapy + Temozolomide - Regimen M Patients were administered Afatinib 40 mg film-coated tablet once daily orally plus radiotherapy (RT) i.e. focal radiation at a dose of 2 Gray per fraction on 5 days per week for 6 weeks (RT phase) (total dose of 60 Gray) plus Temozolomide 75 milligrams per square meter (mg/m2) capsules continuous daily oral dosing. In the maintenance phase after RT, patients stopped TMZ for 4 weeks and restarted TMZ at 150 mg/m2 in cycle 1 and 200 mg/m2 in cycles 2 to 6 on days 1 to 5 of 28-day treatment cycles. Patients were administered Afatinib 40 milligram (mg) film-coated tablet once daily after RT. Dose reductions of Afatinib were allowed if 40 mg or 30 mg were not tolerated. The treatment duration was until tumour progression or occurrence of undue adverse reactions, whichever occurred first. | 7 |
| Afatinib 20 mg, Radiotherapy - Regimen U Patients were administered Afatinib 20 mg film-coated tablet once daily orally plus radiotherapy (RT) i.e. focal radiation at a dose of 2 Gray per fraction on 5 days per week for 6 weeks (RT phase) (total dose of 60 Gray). Patients were administered Afatinib 40 milligram (mg) film-coated tablet once daily in the maintenance phase after RT. The treatment duration was until tumour progression or occurrence of undue adverse reactions, whichever occurred first. Dose reductions were allowed if 40 mg or 30 mg afatinib were not tolerated. | 3 |
| Afatinib 40 mg, Radiotherapy - Regimen U Patients were administered Afatinib 40 mg film-coated tablet once daily orally plus radiotherapy (RT) i.e. focal radiation at a dose of 2 Gray per fraction on 5 days per week for 6 weeks (RT phase) (total dose of 60 Gray). Patients were administered Afatinib 40 milligram (mg) film-coated tablet once daily in the maintenance phase after RT. The treatment duration was until tumour progression or occurrence of undue adverse reactions, whichever occurred first. Dose reductions were allowed if 40 mg or 30 mg afatinib were not tolerated. | 13 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 | 4 | 0 | 6 |
| Overall Study | Dose-limiting toxicity (DLT) | 1 | 0 | 1 | 0 | 0 |
| Overall Study | Other than listed | 1 | 0 | 0 | 0 | 2 |
| Overall Study | Progressive disease | 2 | 6 | 1 | 3 | 5 |
| Overall Study | Protocol Violation | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Afatinib 20 Milligram, Radiotherapy + Temozolomide - Regimen M | Total | Afatinib 40 mg, Radiotherapy - Regimen U | Afatinib 20 mg, Radiotherapy - Regimen U | Afatinib 40 mg, Radiotherapy + Temozolomide - Regimen M | Afatinib 30 mg, Radiotherapy + Temozolomide - Regimen M |
|---|---|---|---|---|---|---|
| Age, Continuous | 48.6 Years STANDARD_DEVIATION 15.7 | 53.4 Years STANDARD_DEVIATION 10.1 | 55.2 Years STANDARD_DEVIATION 9.3 | 52.0 Years STANDARD_DEVIATION 3.6 | 56.0 Years STANDARD_DEVIATION 9.1 | 52.7 Years STANDARD_DEVIATION 7.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 35 Participants | 13 Participants | 3 Participants | 7 Participants | 5 Participants |
| Sex: Female, Male Female | 2 Participants | 11 Participants | 5 Participants | 0 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 5 Participants | 25 Participants | 8 Participants | 3 Participants | 5 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 6 | 0 / 7 | 0 / 20 | 0 / 3 | 3 / 13 | 3 / 16 |
| other Total, other adverse events | 7 / 7 | 6 / 6 | 6 / 7 | 19 / 20 | 3 / 3 | 13 / 13 | 16 / 16 |
| serious Total, serious adverse events | 4 / 7 | 5 / 6 | 3 / 7 | 12 / 20 | 2 / 3 | 10 / 13 | 12 / 16 |
Outcome results
Primary
Maximum Tolerated Dose (MTD) of Afatinib
The MTD was defined as the highest afatinib dose level, at which no more than 1 out of 6 patients experienced drug-related DLT, i.e. the highest afatinib dose with a DLT incidence ≤17%. A separate MTD was determined for afatinib and RT (Regimen U), and for afatinib, TMZ, and RT (Regimen M).
Time frame: 6 weeks
Population: Treated Set (TS); 3 patients were not evaluable for the determination of the maximum tolerated dose replaced in regimen M. 7 patients were excluded from the Afatinib 40 mg arm regimen U count as these were part of the expansion phase after the Maximum Tolerated Dose (MTD) had been determined.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Afatinib 20 Milligram, Radiotherapy + Temozolomide - Regimen M | Maximum Tolerated Dose (MTD) of Afatinib | 30 Milligram (mg) |
| Afatinib 30 mg, Radiotherapy + Temozolomide - Regimen M | Maximum Tolerated Dose (MTD) of Afatinib | 40 Milligram (mg) |
Primary
Number of Patients With Investigator Defined Dose Limiting Toxicities (DLT) During the RT Phase
Adverse event (AE) related to afatinib with any one criteria; Hematological: Common terminology criteria for adverse events (CTCAE) Grade 4 neutropenia (Absolute neutrophil count, including bands \<500/cubic millimeter (mm³)) for \>7 days, CTCAE Grade 3 or 4 neutropenia of any duration associated with fever \>38.3 Celsius, CTCAE Grade 3 thrombocytopenia (platelet count \<50000 - 25000/mm³), All other toxicities of CTCAE Grade ≥3 leading interruption of treatment \> 14 days. Non-hematological: CTCAE Grade ≥3 nausea or vomiting despite appropriate use of standard anti-emetics for ≥3 days, CTCAE Grade ≥3 diarrhea despite appropriate use of standard anti-diarrheal therapy for ≥3 days, CTCAE Grade ≥3 rash despite standard medical management and lasting \>7 days, CTCAE Grade ≥2 cardiac left ventricular function, CTCAE Grade ≥2 worsening of renal function as measured by serum creatinine, newly developed proteinuria or decrease in glomerular filtration rate, All other toxicities of CTCAE Grade ≥3.
Time frame: 6 weeks
Population: Treated Set (TS); 3 patients were not evaluable for the determination of the maximum tolerated dose replaced in regimen M. 7 patients were excluded from the Afatinib 40 mg arm regimen U count as these were part of the expansion phase after the Maximum Tolerated Dose (MTD) had been determined.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Afatinib 20 Milligram, Radiotherapy + Temozolomide - Regimen M | Number of Patients With Investigator Defined Dose Limiting Toxicities (DLT) During the RT Phase | 1 Participants |
| Afatinib 30 mg, Radiotherapy + Temozolomide - Regimen M | Number of Patients With Investigator Defined Dose Limiting Toxicities (DLT) During the RT Phase | 0 Participants |
| Afatinib 40 mg, Radiotherapy + Temozolomide - Regimen M | Number of Patients With Investigator Defined Dose Limiting Toxicities (DLT) During the RT Phase | 2 Participants |
| Afatinib 20 mg, Radiotherapy - Regimen U | Number of Patients With Investigator Defined Dose Limiting Toxicities (DLT) During the RT Phase | 0 Participants |
| Afatinib 40 mg, Radiotherapy - Regimen U | Number of Patients With Investigator Defined Dose Limiting Toxicities (DLT) During the RT Phase | 1 Participants |
Secondary
Concentration of Afatinib in Plasma at Steady State Pre-dose on Days 8, 15 and 29
Concentration of afatinib in plasma at steady state pre-dose (Cpre,ss) on days 8, 15 and 29.
Time frame: Pharmacokinetic blood sample were taken at 5 minutes before drug on days 8, 15 and 29 and 1, 3 and 6 hours after drug administration on day 15
Population: Treated Set; only evaluable patients were included in the pharmacokinetic analysis
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Afatinib 20 Milligram, Radiotherapy + Temozolomide - Regimen M | Concentration of Afatinib in Plasma at Steady State Pre-dose on Days 8, 15 and 29 | Cpre, ss, 8 | 4.4 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 40.2 |
| Afatinib 20 Milligram, Radiotherapy + Temozolomide - Regimen M | Concentration of Afatinib in Plasma at Steady State Pre-dose on Days 8, 15 and 29 | Cpre, ss, 29 | 5.3 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 92 |
| Afatinib 20 Milligram, Radiotherapy + Temozolomide - Regimen M | Concentration of Afatinib in Plasma at Steady State Pre-dose on Days 8, 15 and 29 | Cpre, ss, 15 | 5.6 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 55.1 |
| Afatinib 30 mg, Radiotherapy + Temozolomide - Regimen M | Concentration of Afatinib in Plasma at Steady State Pre-dose on Days 8, 15 and 29 | Cpre, ss, 15 | 9.6 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 54.3 |
| Afatinib 30 mg, Radiotherapy + Temozolomide - Regimen M | Concentration of Afatinib in Plasma at Steady State Pre-dose on Days 8, 15 and 29 | Cpre, ss, 8 | 10.7 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 70.3 |
| Afatinib 30 mg, Radiotherapy + Temozolomide - Regimen M | Concentration of Afatinib in Plasma at Steady State Pre-dose on Days 8, 15 and 29 | Cpre, ss, 29 | 17.8 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 15.6 |
| Afatinib 40 mg, Radiotherapy + Temozolomide - Regimen M | Concentration of Afatinib in Plasma at Steady State Pre-dose on Days 8, 15 and 29 | Cpre, ss, 15 | 16.8 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 59.5 |
| Afatinib 40 mg, Radiotherapy + Temozolomide - Regimen M | Concentration of Afatinib in Plasma at Steady State Pre-dose on Days 8, 15 and 29 | Cpre, ss, 8 | 15.7 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 32.8 |
| Afatinib 40 mg, Radiotherapy + Temozolomide - Regimen M | Concentration of Afatinib in Plasma at Steady State Pre-dose on Days 8, 15 and 29 | Cpre, ss, 29 | 17.4 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 56.1 |
| Afatinib 20 mg, Radiotherapy - Regimen U | Concentration of Afatinib in Plasma at Steady State Pre-dose on Days 8, 15 and 29 | Cpre, ss, 8 | 4.9 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 32.9 |
| Afatinib 20 mg, Radiotherapy - Regimen U | Concentration of Afatinib in Plasma at Steady State Pre-dose on Days 8, 15 and 29 | Cpre, ss, 29 | 5.0 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 53.3 |
| Afatinib 20 mg, Radiotherapy - Regimen U | Concentration of Afatinib in Plasma at Steady State Pre-dose on Days 8, 15 and 29 | Cpre, ss, 15 | 4.4 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 177 |
| Afatinib 40 mg, Radiotherapy - Regimen U | Concentration of Afatinib in Plasma at Steady State Pre-dose on Days 8, 15 and 29 | Cpre, ss, 15 | 18.9 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 35.5 |
| Afatinib 40 mg, Radiotherapy - Regimen U | Concentration of Afatinib in Plasma at Steady State Pre-dose on Days 8, 15 and 29 | Cpre, ss, 8 | 16.7 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 40.2 |
| Afatinib 40 mg, Radiotherapy - Regimen U | Concentration of Afatinib in Plasma at Steady State Pre-dose on Days 8, 15 and 29 | Cpre, ss, 29 | 16.1 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 40.7 |
Secondary
Incidence and Intensity of Adverse Events (AE) According to Common Terminology Criteria of Adverse Events (CTCAE v.3.0)
Incidence and intensity of adverse events (AE) according to Common Terminology Criteria of Adverse Events (CTCAE v.3.0). The CTCAE grades are: 1 (mild AE), 2 (moderate AE), 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related to AE).
Time frame: From the first administration of trial medication until 4 weeks after the last administration of trial medication, up to approximately 338 weeks
Population: Treated Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Afatinib 20 Milligram, Radiotherapy + Temozolomide - Regimen M | Incidence and Intensity of Adverse Events (AE) According to Common Terminology Criteria of Adverse Events (CTCAE v.3.0) | Grade 2 | 0 Participants |
| Afatinib 20 Milligram, Radiotherapy + Temozolomide - Regimen M | Incidence and Intensity of Adverse Events (AE) According to Common Terminology Criteria of Adverse Events (CTCAE v.3.0) | Grade 1 | 0 Participants |
| Afatinib 20 Milligram, Radiotherapy + Temozolomide - Regimen M | Incidence and Intensity of Adverse Events (AE) According to Common Terminology Criteria of Adverse Events (CTCAE v.3.0) | Grade 3 | 4 Participants |
| Afatinib 20 Milligram, Radiotherapy + Temozolomide - Regimen M | Incidence and Intensity of Adverse Events (AE) According to Common Terminology Criteria of Adverse Events (CTCAE v.3.0) | Grade 5 | 0 Participants |
| Afatinib 20 Milligram, Radiotherapy + Temozolomide - Regimen M | Incidence and Intensity of Adverse Events (AE) According to Common Terminology Criteria of Adverse Events (CTCAE v.3.0) | Grade 4 | 3 Participants |
| Afatinib 30 mg, Radiotherapy + Temozolomide - Regimen M | Incidence and Intensity of Adverse Events (AE) According to Common Terminology Criteria of Adverse Events (CTCAE v.3.0) | Grade 3 | 4 Participants |
| Afatinib 30 mg, Radiotherapy + Temozolomide - Regimen M | Incidence and Intensity of Adverse Events (AE) According to Common Terminology Criteria of Adverse Events (CTCAE v.3.0) | Grade 1 | 0 Participants |
| Afatinib 30 mg, Radiotherapy + Temozolomide - Regimen M | Incidence and Intensity of Adverse Events (AE) According to Common Terminology Criteria of Adverse Events (CTCAE v.3.0) | Grade 2 | 2 Participants |
| Afatinib 30 mg, Radiotherapy + Temozolomide - Regimen M | Incidence and Intensity of Adverse Events (AE) According to Common Terminology Criteria of Adverse Events (CTCAE v.3.0) | Grade 4 | 0 Participants |
| Afatinib 30 mg, Radiotherapy + Temozolomide - Regimen M | Incidence and Intensity of Adverse Events (AE) According to Common Terminology Criteria of Adverse Events (CTCAE v.3.0) | Grade 5 | 0 Participants |
| Afatinib 40 mg, Radiotherapy + Temozolomide - Regimen M | Incidence and Intensity of Adverse Events (AE) According to Common Terminology Criteria of Adverse Events (CTCAE v.3.0) | Grade 2 | 1 Participants |
| Afatinib 40 mg, Radiotherapy + Temozolomide - Regimen M | Incidence and Intensity of Adverse Events (AE) According to Common Terminology Criteria of Adverse Events (CTCAE v.3.0) | Grade 4 | 1 Participants |
| Afatinib 40 mg, Radiotherapy + Temozolomide - Regimen M | Incidence and Intensity of Adverse Events (AE) According to Common Terminology Criteria of Adverse Events (CTCAE v.3.0) | Grade 3 | 4 Participants |
| Afatinib 40 mg, Radiotherapy + Temozolomide - Regimen M | Incidence and Intensity of Adverse Events (AE) According to Common Terminology Criteria of Adverse Events (CTCAE v.3.0) | Grade 5 | 0 Participants |
| Afatinib 40 mg, Radiotherapy + Temozolomide - Regimen M | Incidence and Intensity of Adverse Events (AE) According to Common Terminology Criteria of Adverse Events (CTCAE v.3.0) | Grade 1 | 1 Participants |
| Afatinib 20 mg, Radiotherapy - Regimen U | Incidence and Intensity of Adverse Events (AE) According to Common Terminology Criteria of Adverse Events (CTCAE v.3.0) | Grade 4 | 0 Participants |
| Afatinib 20 mg, Radiotherapy - Regimen U | Incidence and Intensity of Adverse Events (AE) According to Common Terminology Criteria of Adverse Events (CTCAE v.3.0) | Grade 3 | 2 Participants |
| Afatinib 20 mg, Radiotherapy - Regimen U | Incidence and Intensity of Adverse Events (AE) According to Common Terminology Criteria of Adverse Events (CTCAE v.3.0) | Grade 1 | 0 Participants |
| Afatinib 20 mg, Radiotherapy - Regimen U | Incidence and Intensity of Adverse Events (AE) According to Common Terminology Criteria of Adverse Events (CTCAE v.3.0) | Grade 5 | 0 Participants |
| Afatinib 20 mg, Radiotherapy - Regimen U | Incidence and Intensity of Adverse Events (AE) According to Common Terminology Criteria of Adverse Events (CTCAE v.3.0) | Grade 2 | 1 Participants |
| Afatinib 40 mg, Radiotherapy - Regimen U | Incidence and Intensity of Adverse Events (AE) According to Common Terminology Criteria of Adverse Events (CTCAE v.3.0) | Grade 1 | 1 Participants |
| Afatinib 40 mg, Radiotherapy - Regimen U | Incidence and Intensity of Adverse Events (AE) According to Common Terminology Criteria of Adverse Events (CTCAE v.3.0) | Grade 3 | 5 Participants |
| Afatinib 40 mg, Radiotherapy - Regimen U | Incidence and Intensity of Adverse Events (AE) According to Common Terminology Criteria of Adverse Events (CTCAE v.3.0) | Grade 5 | 3 Participants |
| Afatinib 40 mg, Radiotherapy - Regimen U | Incidence and Intensity of Adverse Events (AE) According to Common Terminology Criteria of Adverse Events (CTCAE v.3.0) | Grade 4 | 2 Participants |
| Afatinib 40 mg, Radiotherapy - Regimen U | Incidence and Intensity of Adverse Events (AE) According to Common Terminology Criteria of Adverse Events (CTCAE v.3.0) | Grade 2 | 2 Participants |
Secondary
The Objective Tumour Response According to the Macdonald Criteria
Objective response was defined as a best overall response of complete response (CR) or partial response (PR). The best overall response was the best overall response to trial medication according to the Macdonald criteria recorded since the first administration of trial medication and until the earliest of disease progression, death, or start of further anti-cancer treatment. Tumour response was assessed based on local radiological image evaluation by the investigators according to the Macdonald criteria: Complete Response (CR): Disappearance of all enhancing tumour on consecutive Magnetic resonance imaging (MRI) scans at least 28 days apart, off steroids, and neurologically stable or improved. Partial Response (PR): At least 50% reduction in size of enhancing tumour on consecutive MRI scans at least 28 days apart, steroids stable or reduced, and neurologically stable or improved.
Time frame: From the first administration of trial medication until 4 weeks after the last administration of trial medication, up to approximately 338 weeks
Population: Treated Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Afatinib 20 Milligram, Radiotherapy + Temozolomide - Regimen M | The Objective Tumour Response According to the Macdonald Criteria | No | 5 Participants |
| Afatinib 20 Milligram, Radiotherapy + Temozolomide - Regimen M | The Objective Tumour Response According to the Macdonald Criteria | Missing | 0 Participants |
| Afatinib 20 Milligram, Radiotherapy + Temozolomide - Regimen M | The Objective Tumour Response According to the Macdonald Criteria | Yes | 2 Participants |
| Afatinib 30 mg, Radiotherapy + Temozolomide - Regimen M | The Objective Tumour Response According to the Macdonald Criteria | Yes | 3 Participants |
| Afatinib 30 mg, Radiotherapy + Temozolomide - Regimen M | The Objective Tumour Response According to the Macdonald Criteria | No | 3 Participants |
| Afatinib 30 mg, Radiotherapy + Temozolomide - Regimen M | The Objective Tumour Response According to the Macdonald Criteria | Missing | 0 Participants |
| Afatinib 40 mg, Radiotherapy + Temozolomide - Regimen M | The Objective Tumour Response According to the Macdonald Criteria | Yes | 0 Participants |
| Afatinib 40 mg, Radiotherapy + Temozolomide - Regimen M | The Objective Tumour Response According to the Macdonald Criteria | No | 5 Participants |
| Afatinib 40 mg, Radiotherapy + Temozolomide - Regimen M | The Objective Tumour Response According to the Macdonald Criteria | Missing | 2 Participants |
| Afatinib 20 mg, Radiotherapy - Regimen U | The Objective Tumour Response According to the Macdonald Criteria | No | 3 Participants |
| Afatinib 20 mg, Radiotherapy - Regimen U | The Objective Tumour Response According to the Macdonald Criteria | Missing | 0 Participants |
| Afatinib 20 mg, Radiotherapy - Regimen U | The Objective Tumour Response According to the Macdonald Criteria | Yes | 0 Participants |
| Afatinib 40 mg, Radiotherapy - Regimen U | The Objective Tumour Response According to the Macdonald Criteria | Yes | 1 Participants |
| Afatinib 40 mg, Radiotherapy - Regimen U | The Objective Tumour Response According to the Macdonald Criteria | No | 10 Participants |
| Afatinib 40 mg, Radiotherapy - Regimen U | The Objective Tumour Response According to the Macdonald Criteria | Missing | 2 Participants |