Trial Outcomes & Findings for BIBW 2992 (Afatinib) and Vinorelbine in Japanese Patients With Advanced Solid Tumours (NCT NCT01214616)
NCT ID: NCT01214616
Last Updated: 2025-02-07
Results Overview
DLTs and Maximum Tolerated Dose (MTD) of afatinib in combination with vinorelbine iv. (MTD = not determined)
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
17 participants
Primary outcome timeframe
during 1st course
Results posted on
2025-02-07
Participant Flow
Participant milestones
| Measure |
Afatinib 20 mg With Vinorelbine 25 mg/m^2 (Cohort 1)
Afatinib 20 mg oral administration once a day with vinorelbine 25 mg/m\^2 intravenous injection weekly
|
Afatinib 40 mg With Vinorelbine 25 mg/m^2 (Cohort 2)
Afatinib 40 mg oral administration once a day with vinorelbine 25 mg/m\^2 intravenous injection weekly
|
Afatinib 40 mg With Vinorelbine 20 mg/m^2 (Cohort 2a)
Afatinib 40 mg oral administration once a day with vinorelbine 20 mg/m\^2 intravenous injection weekly
|
Afatinib 40 mg With Vinorelbine 25 mg/m^2 (Cohort 3)
Afatinib 40 mg oral administration once a day with vinorelbine 25 mg/m\^2 intravenous injection weekly; allowed for vinorelbine dose to be skipped for Common Toxicity Criteria for Adverse Effects (CTCAE) Grade 2 or worse neutropenia or thrombocytopenia
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
3
|
5
|
3
|
6
|
|
Overall Study
COMPLETED
|
0
|
0
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
3
|
5
|
3
|
6
|
Reasons for withdrawal
| Measure |
Afatinib 20 mg With Vinorelbine 25 mg/m^2 (Cohort 1)
Afatinib 20 mg oral administration once a day with vinorelbine 25 mg/m\^2 intravenous injection weekly
|
Afatinib 40 mg With Vinorelbine 25 mg/m^2 (Cohort 2)
Afatinib 40 mg oral administration once a day with vinorelbine 25 mg/m\^2 intravenous injection weekly
|
Afatinib 40 mg With Vinorelbine 20 mg/m^2 (Cohort 2a)
Afatinib 40 mg oral administration once a day with vinorelbine 20 mg/m\^2 intravenous injection weekly
|
Afatinib 40 mg With Vinorelbine 25 mg/m^2 (Cohort 3)
Afatinib 40 mg oral administration once a day with vinorelbine 25 mg/m\^2 intravenous injection weekly; allowed for vinorelbine dose to be skipped for Common Toxicity Criteria for Adverse Effects (CTCAE) Grade 2 or worse neutropenia or thrombocytopenia
|
|---|---|---|---|---|
|
Overall Study
Progressive disease
|
2
|
2
|
2
|
4
|
|
Overall Study
Dose limiting toxicity
|
0
|
2
|
0
|
0
|
|
Overall Study
Other adverse events
|
0
|
1
|
1
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
0
|
1
|
Baseline Characteristics
BIBW 2992 (Afatinib) and Vinorelbine in Japanese Patients With Advanced Solid Tumours
Baseline characteristics by cohort
| Measure |
Afatinib 20 mg With Vinorelbine 25 mg/m^2 (Cohort 1)
n=3 Participants
Afatinib 20 mg oral administration once a day with vinorelbine 25 mg/m\^2 intravenous injection weekly
|
Afatinib 40 mg With Vinorelbine 25 mg/m^2 (Cohort 2)
n=5 Participants
Afatinib 40 mg oral administration once a day with vinorelbine 25 mg/m\^2 intravenous injection weekly
|
Afatinib 40 mg With Vinorelbine 20 mg/m^2 (Cohort 2a)
n=3 Participants
Afatinib 40 mg oral administration once a day with vinorelbine 20 mg/m\^2 intravenous injection weekly
|
Afatinib 40 mg With Vinorelbine 25 mg/m^2 (Cohort 3)
n=6 Participants
Afatinib 40 mg oral administration once a day with vinorelbine 25 mg/m\^2 intravenous injection weekly; allowed for vinorelbine dose to be skipped for Common Toxicity Criteria for Adverse Effects (CTCAE) Grade 2 or worse neutropenia or thrombocytopenia
|
Total
n=17 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
63.0 years
STANDARD_DEVIATION 2.0 • n=5 Participants
|
58.8 years
STANDARD_DEVIATION 4.1 • n=7 Participants
|
52.7 years
STANDARD_DEVIATION 11.8 • n=5 Participants
|
52.3 years
STANDARD_DEVIATION 11.0 • n=4 Participants
|
56.2 years
STANDARD_DEVIATION 8.9 • n=21 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
10 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
7 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: during 1st coursePopulation: Treated set: all patients who received at least 1 dose of investigational medication (afatinib or vinorelbine)
DLTs and Maximum Tolerated Dose (MTD) of afatinib in combination with vinorelbine iv. (MTD = not determined)
Outcome measures
| Measure |
Afatinib 40 mg Without Vinorelbine
n=6 Participants
Afatinib 40 mg oral administration once a day without vinorelbine intravenous injection weekly.
All patient was assigned as "20 mg afatinib with vinorelbine 25 mg/m2" or "40 mg afatinib with vinorelbine 20 mg/m2" or "40 mg afatinib with vinorelbine 25 mg/m2".
On day 21 (after 20 doses of afatinib), 6 days passed after last vinorelbine administration (day 15) and PK parameters of afatinib on day 21 were treated as "without vinorelbine" because no large effect of vinorelbine is expected from PK point of view.
|
Afatinib 20 mg With Vinorelbine
n=3 Participants
Afatinib 20 mg oral administration once a day with vinorelbine intravenous injection weekly.
All patient was assigned as "20 mg afatinib with vinorelbine 25 mg/m2" or "40 mg afatinib with vinorelbine 20 mg/m2" or "40 mg afatinib with vinorelbine 25 mg/m2".
On day 21 (after 20 doses of afatinib), 6 days passed after last vinorelbine administration (day 15) and PK parameters of afatinib on day 21 were treated as "without vinorelbine" because no large effect of vinorelbine is expected from PK point of view.
|
Afatinib 20 mg Without Vinorelbine
n=5 Participants
Afatinib 20 mg oral administration once a day without vinorelbine intravenous injection weekly.
All patient was assigned as "20 mg afatinib with vinorelbine 25 mg/m2" or "40 mg afatinib with vinorelbine 20 mg/m2" or "40 mg afatinib with vinorelbine 25 mg/m2".
On day 21 (after 20 doses of afatinib), 6 days passed after last vinorelbine administration (day 15) and PK parameters of afatinib on day 21 were treated as "without vinorelbine" because no large effect of vinorelbine is expected from PK point of view.
|
Afatinib 40 mg With Vinorelbine
n=3 Participants
Afatinib 40 mg oral administration once a day with vinorelbine intravenous injection weekly.
All patient was assigned as "20 mg afatinib with vinorelbine 25 mg/m2" or "40 mg afatinib with vinorelbine 20 mg/m2" or "40 mg afatinib with vinorelbine 25 mg/m2".
On day 21 (after 20 doses of afatinib), 6 days passed after last vinorelbine administration (day 15) and PK parameters of afatinib on day 21 were treated as "without vinorelbine" because no large effect of vinorelbine is expected from PK point of view.
|
|---|---|---|---|---|
|
Number of Patients With Dose Limiting Toxicities (DLTs) During 1st Course
|
1 participants
|
0 participants
|
3 participants
|
0 participants
|
PRIMARY outcome
Timeframe: during the treatment period or up to 28 days after the completion of drug administration, up to 730 daysPopulation: Treated set
Number of patients with drug-related adverse events
Outcome measures
| Measure |
Afatinib 40 mg Without Vinorelbine
n=6 Participants
Afatinib 40 mg oral administration once a day without vinorelbine intravenous injection weekly.
All patient was assigned as "20 mg afatinib with vinorelbine 25 mg/m2" or "40 mg afatinib with vinorelbine 20 mg/m2" or "40 mg afatinib with vinorelbine 25 mg/m2".
On day 21 (after 20 doses of afatinib), 6 days passed after last vinorelbine administration (day 15) and PK parameters of afatinib on day 21 were treated as "without vinorelbine" because no large effect of vinorelbine is expected from PK point of view.
|
Afatinib 20 mg With Vinorelbine
n=3 Participants
Afatinib 20 mg oral administration once a day with vinorelbine intravenous injection weekly.
All patient was assigned as "20 mg afatinib with vinorelbine 25 mg/m2" or "40 mg afatinib with vinorelbine 20 mg/m2" or "40 mg afatinib with vinorelbine 25 mg/m2".
On day 21 (after 20 doses of afatinib), 6 days passed after last vinorelbine administration (day 15) and PK parameters of afatinib on day 21 were treated as "without vinorelbine" because no large effect of vinorelbine is expected from PK point of view.
|
Afatinib 20 mg Without Vinorelbine
n=5 Participants
Afatinib 20 mg oral administration once a day without vinorelbine intravenous injection weekly.
All patient was assigned as "20 mg afatinib with vinorelbine 25 mg/m2" or "40 mg afatinib with vinorelbine 20 mg/m2" or "40 mg afatinib with vinorelbine 25 mg/m2".
On day 21 (after 20 doses of afatinib), 6 days passed after last vinorelbine administration (day 15) and PK parameters of afatinib on day 21 were treated as "without vinorelbine" because no large effect of vinorelbine is expected from PK point of view.
|
Afatinib 40 mg With Vinorelbine
n=3 Participants
Afatinib 40 mg oral administration once a day with vinorelbine intravenous injection weekly.
All patient was assigned as "20 mg afatinib with vinorelbine 25 mg/m2" or "40 mg afatinib with vinorelbine 20 mg/m2" or "40 mg afatinib with vinorelbine 25 mg/m2".
On day 21 (after 20 doses of afatinib), 6 days passed after last vinorelbine administration (day 15) and PK parameters of afatinib on day 21 were treated as "without vinorelbine" because no large effect of vinorelbine is expected from PK point of view.
|
|---|---|---|---|---|
|
Drug-related Adverse Events
|
6 participants
|
3 participants
|
5 participants
|
3 participants
|
SECONDARY outcome
Timeframe: pre-dose, 1, 2, 3, 4, 6, 7hours, and 23hours55minutes after 7th or 14th or 21th dose (as "with Vinorelbine") and 20th dose (as "without Vinorelbine")Population: Treated set
area under the plasma concentration-time curve following dose at steady state over the dosing interval τ
Outcome measures
| Measure |
Afatinib 40 mg Without Vinorelbine
n=8 Participants
Afatinib 40 mg oral administration once a day without vinorelbine intravenous injection weekly.
All patient was assigned as "20 mg afatinib with vinorelbine 25 mg/m2" or "40 mg afatinib with vinorelbine 20 mg/m2" or "40 mg afatinib with vinorelbine 25 mg/m2".
On day 21 (after 20 doses of afatinib), 6 days passed after last vinorelbine administration (day 15) and PK parameters of afatinib on day 21 were treated as "without vinorelbine" because no large effect of vinorelbine is expected from PK point of view.
|
Afatinib 20 mg With Vinorelbine
n=2 Participants
Afatinib 20 mg oral administration once a day with vinorelbine intravenous injection weekly.
All patient was assigned as "20 mg afatinib with vinorelbine 25 mg/m2" or "40 mg afatinib with vinorelbine 20 mg/m2" or "40 mg afatinib with vinorelbine 25 mg/m2".
On day 21 (after 20 doses of afatinib), 6 days passed after last vinorelbine administration (day 15) and PK parameters of afatinib on day 21 were treated as "without vinorelbine" because no large effect of vinorelbine is expected from PK point of view.
|
Afatinib 20 mg Without Vinorelbine
n=3 Participants
Afatinib 20 mg oral administration once a day without vinorelbine intravenous injection weekly.
All patient was assigned as "20 mg afatinib with vinorelbine 25 mg/m2" or "40 mg afatinib with vinorelbine 20 mg/m2" or "40 mg afatinib with vinorelbine 25 mg/m2".
On day 21 (after 20 doses of afatinib), 6 days passed after last vinorelbine administration (day 15) and PK parameters of afatinib on day 21 were treated as "without vinorelbine" because no large effect of vinorelbine is expected from PK point of view.
|
Afatinib 40 mg With Vinorelbine
n=9 Participants
Afatinib 40 mg oral administration once a day with vinorelbine intravenous injection weekly.
All patient was assigned as "20 mg afatinib with vinorelbine 25 mg/m2" or "40 mg afatinib with vinorelbine 20 mg/m2" or "40 mg afatinib with vinorelbine 25 mg/m2".
On day 21 (after 20 doses of afatinib), 6 days passed after last vinorelbine administration (day 15) and PK parameters of afatinib on day 21 were treated as "without vinorelbine" because no large effect of vinorelbine is expected from PK point of view.
|
|---|---|---|---|---|
|
AUCτ,ss for Afatinib
|
1010 ng*h/mL
Geometric Coefficient of Variation 70.1
|
329 ng*h/mL
Geometric Coefficient of Variation 79.5
|
404 ng*h/mL
Geometric Coefficient of Variation 63.9
|
866 ng*h/mL
Geometric Coefficient of Variation 55.3
|
SECONDARY outcome
Timeframe: pre-dose, 1, 2, 3, 4, 6, 7hours, and 23hours55minutes after 7th or 14th or 21th dose (as "with Vinorelbine") and 20th dose (as "without Vinorelbine")Population: Treated set
maximum measured plasma concentration at steady state
Outcome measures
| Measure |
Afatinib 40 mg Without Vinorelbine
n=9 Participants
Afatinib 40 mg oral administration once a day without vinorelbine intravenous injection weekly.
All patient was assigned as "20 mg afatinib with vinorelbine 25 mg/m2" or "40 mg afatinib with vinorelbine 20 mg/m2" or "40 mg afatinib with vinorelbine 25 mg/m2".
On day 21 (after 20 doses of afatinib), 6 days passed after last vinorelbine administration (day 15) and PK parameters of afatinib on day 21 were treated as "without vinorelbine" because no large effect of vinorelbine is expected from PK point of view.
|
Afatinib 20 mg With Vinorelbine
n=3 Participants
Afatinib 20 mg oral administration once a day with vinorelbine intravenous injection weekly.
All patient was assigned as "20 mg afatinib with vinorelbine 25 mg/m2" or "40 mg afatinib with vinorelbine 20 mg/m2" or "40 mg afatinib with vinorelbine 25 mg/m2".
On day 21 (after 20 doses of afatinib), 6 days passed after last vinorelbine administration (day 15) and PK parameters of afatinib on day 21 were treated as "without vinorelbine" because no large effect of vinorelbine is expected from PK point of view.
|
Afatinib 20 mg Without Vinorelbine
n=3 Participants
Afatinib 20 mg oral administration once a day without vinorelbine intravenous injection weekly.
All patient was assigned as "20 mg afatinib with vinorelbine 25 mg/m2" or "40 mg afatinib with vinorelbine 20 mg/m2" or "40 mg afatinib with vinorelbine 25 mg/m2".
On day 21 (after 20 doses of afatinib), 6 days passed after last vinorelbine administration (day 15) and PK parameters of afatinib on day 21 were treated as "without vinorelbine" because no large effect of vinorelbine is expected from PK point of view.
|
Afatinib 40 mg With Vinorelbine
n=10 Participants
Afatinib 40 mg oral administration once a day with vinorelbine intravenous injection weekly.
All patient was assigned as "20 mg afatinib with vinorelbine 25 mg/m2" or "40 mg afatinib with vinorelbine 20 mg/m2" or "40 mg afatinib with vinorelbine 25 mg/m2".
On day 21 (after 20 doses of afatinib), 6 days passed after last vinorelbine administration (day 15) and PK parameters of afatinib on day 21 were treated as "without vinorelbine" because no large effect of vinorelbine is expected from PK point of view.
|
|---|---|---|---|---|
|
Cmax,ss for Afatinib
|
57.1 ng/mL
Geometric Coefficient of Variation 76.4
|
28.8 ng/mL
Geometric Coefficient of Variation 87.3
|
19.6 ng/mL
Geometric Coefficient of Variation 50.6
|
52.5 ng/mL
Geometric Coefficient of Variation 46.8
|
SECONDARY outcome
Timeframe: predose, 10minutes, 0.5, 1, 4, 7 hours, 23hours55minutes after 2nd or 3rd or 4th dose (as "with afatinib") and 1st dose (as "without afatinib")Population: Treated set
area under the blood concentration-time curve of the analyte over the time interval from 0 extrapolated to infinity
Outcome measures
| Measure |
Afatinib 40 mg Without Vinorelbine
n=13 Participants
Afatinib 40 mg oral administration once a day without vinorelbine intravenous injection weekly.
All patient was assigned as "20 mg afatinib with vinorelbine 25 mg/m2" or "40 mg afatinib with vinorelbine 20 mg/m2" or "40 mg afatinib with vinorelbine 25 mg/m2".
On day 21 (after 20 doses of afatinib), 6 days passed after last vinorelbine administration (day 15) and PK parameters of afatinib on day 21 were treated as "without vinorelbine" because no large effect of vinorelbine is expected from PK point of view.
|
Afatinib 20 mg With Vinorelbine
n=3 Participants
Afatinib 20 mg oral administration once a day with vinorelbine intravenous injection weekly.
All patient was assigned as "20 mg afatinib with vinorelbine 25 mg/m2" or "40 mg afatinib with vinorelbine 20 mg/m2" or "40 mg afatinib with vinorelbine 25 mg/m2".
On day 21 (after 20 doses of afatinib), 6 days passed after last vinorelbine administration (day 15) and PK parameters of afatinib on day 21 were treated as "without vinorelbine" because no large effect of vinorelbine is expected from PK point of view.
|
Afatinib 20 mg Without Vinorelbine
n=3 Participants
Afatinib 20 mg oral administration once a day without vinorelbine intravenous injection weekly.
All patient was assigned as "20 mg afatinib with vinorelbine 25 mg/m2" or "40 mg afatinib with vinorelbine 20 mg/m2" or "40 mg afatinib with vinorelbine 25 mg/m2".
On day 21 (after 20 doses of afatinib), 6 days passed after last vinorelbine administration (day 15) and PK parameters of afatinib on day 21 were treated as "without vinorelbine" because no large effect of vinorelbine is expected from PK point of view.
|
Afatinib 40 mg With Vinorelbine
n=8 Participants
Afatinib 40 mg oral administration once a day with vinorelbine intravenous injection weekly.
All patient was assigned as "20 mg afatinib with vinorelbine 25 mg/m2" or "40 mg afatinib with vinorelbine 20 mg/m2" or "40 mg afatinib with vinorelbine 25 mg/m2".
On day 21 (after 20 doses of afatinib), 6 days passed after last vinorelbine administration (day 15) and PK parameters of afatinib on day 21 were treated as "without vinorelbine" because no large effect of vinorelbine is expected from PK point of view.
|
|---|---|---|---|---|
|
AUC0-∞ for Vinorelbine
|
860 ng*h/mL
Geometric Coefficient of Variation 21.2
|
763 ng*h/mL
Geometric Coefficient of Variation 30.5
|
691 ng*h/mL
Geometric Coefficient of Variation 18.8
|
934 ng*h/mL
Geometric Coefficient of Variation 24.9
|
SECONDARY outcome
Timeframe: predose, 10minutes, 0.5, 1, 4, 7 hours, 23hours55minutes after 2nd or 3rd or 4th dose (as "with afatinib") and 1st dose (as "without afatinib")Population: Treated set
maximum measured blood concentration
Outcome measures
| Measure |
Afatinib 40 mg Without Vinorelbine
n=13 Participants
Afatinib 40 mg oral administration once a day without vinorelbine intravenous injection weekly.
All patient was assigned as "20 mg afatinib with vinorelbine 25 mg/m2" or "40 mg afatinib with vinorelbine 20 mg/m2" or "40 mg afatinib with vinorelbine 25 mg/m2".
On day 21 (after 20 doses of afatinib), 6 days passed after last vinorelbine administration (day 15) and PK parameters of afatinib on day 21 were treated as "without vinorelbine" because no large effect of vinorelbine is expected from PK point of view.
|
Afatinib 20 mg With Vinorelbine
n=4 Participants
Afatinib 20 mg oral administration once a day with vinorelbine intravenous injection weekly.
All patient was assigned as "20 mg afatinib with vinorelbine 25 mg/m2" or "40 mg afatinib with vinorelbine 20 mg/m2" or "40 mg afatinib with vinorelbine 25 mg/m2".
On day 21 (after 20 doses of afatinib), 6 days passed after last vinorelbine administration (day 15) and PK parameters of afatinib on day 21 were treated as "without vinorelbine" because no large effect of vinorelbine is expected from PK point of view.
|
Afatinib 20 mg Without Vinorelbine
n=3 Participants
Afatinib 20 mg oral administration once a day without vinorelbine intravenous injection weekly.
All patient was assigned as "20 mg afatinib with vinorelbine 25 mg/m2" or "40 mg afatinib with vinorelbine 20 mg/m2" or "40 mg afatinib with vinorelbine 25 mg/m2".
On day 21 (after 20 doses of afatinib), 6 days passed after last vinorelbine administration (day 15) and PK parameters of afatinib on day 21 were treated as "without vinorelbine" because no large effect of vinorelbine is expected from PK point of view.
|
Afatinib 40 mg With Vinorelbine
n=9 Participants
Afatinib 40 mg oral administration once a day with vinorelbine intravenous injection weekly.
All patient was assigned as "20 mg afatinib with vinorelbine 25 mg/m2" or "40 mg afatinib with vinorelbine 20 mg/m2" or "40 mg afatinib with vinorelbine 25 mg/m2".
On day 21 (after 20 doses of afatinib), 6 days passed after last vinorelbine administration (day 15) and PK parameters of afatinib on day 21 were treated as "without vinorelbine" because no large effect of vinorelbine is expected from PK point of view.
|
|---|---|---|---|---|
|
Cmax for Vinorelbine
|
1330 ng/mL
Geometric Coefficient of Variation 25.3
|
1120 ng/mL
Geometric Coefficient of Variation 23.0
|
1380 ng/mL
Geometric Coefficient of Variation 8.73
|
1160 ng/mL
Geometric Coefficient of Variation 36.4
|
SECONDARY outcome
Timeframe: Pre-treatment, every 8 weeks after start of study treatment, end of treatmentPopulation: Treated set
According to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria and assessed by CT or MRI: Complete Response (CR), disappearance of all target and non-target lesions; Partial Response (PR), at least a 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR."
Outcome measures
| Measure |
Afatinib 40 mg Without Vinorelbine
n=6 Participants
Afatinib 40 mg oral administration once a day without vinorelbine intravenous injection weekly.
All patient was assigned as "20 mg afatinib with vinorelbine 25 mg/m2" or "40 mg afatinib with vinorelbine 20 mg/m2" or "40 mg afatinib with vinorelbine 25 mg/m2".
On day 21 (after 20 doses of afatinib), 6 days passed after last vinorelbine administration (day 15) and PK parameters of afatinib on day 21 were treated as "without vinorelbine" because no large effect of vinorelbine is expected from PK point of view.
|
Afatinib 20 mg With Vinorelbine
n=3 Participants
Afatinib 20 mg oral administration once a day with vinorelbine intravenous injection weekly.
All patient was assigned as "20 mg afatinib with vinorelbine 25 mg/m2" or "40 mg afatinib with vinorelbine 20 mg/m2" or "40 mg afatinib with vinorelbine 25 mg/m2".
On day 21 (after 20 doses of afatinib), 6 days passed after last vinorelbine administration (day 15) and PK parameters of afatinib on day 21 were treated as "without vinorelbine" because no large effect of vinorelbine is expected from PK point of view.
|
Afatinib 20 mg Without Vinorelbine
n=5 Participants
Afatinib 20 mg oral administration once a day without vinorelbine intravenous injection weekly.
All patient was assigned as "20 mg afatinib with vinorelbine 25 mg/m2" or "40 mg afatinib with vinorelbine 20 mg/m2" or "40 mg afatinib with vinorelbine 25 mg/m2".
On day 21 (after 20 doses of afatinib), 6 days passed after last vinorelbine administration (day 15) and PK parameters of afatinib on day 21 were treated as "without vinorelbine" because no large effect of vinorelbine is expected from PK point of view.
|
Afatinib 40 mg With Vinorelbine
n=3 Participants
Afatinib 40 mg oral administration once a day with vinorelbine intravenous injection weekly.
All patient was assigned as "20 mg afatinib with vinorelbine 25 mg/m2" or "40 mg afatinib with vinorelbine 20 mg/m2" or "40 mg afatinib with vinorelbine 25 mg/m2".
On day 21 (after 20 doses of afatinib), 6 days passed after last vinorelbine administration (day 15) and PK parameters of afatinib on day 21 were treated as "without vinorelbine" because no large effect of vinorelbine is expected from PK point of view.
|
|---|---|---|---|---|
|
Objective Tumour Response
|
1 participants
|
0 participants
|
0 participants
|
1 participants
|
Adverse Events
Afatinib 20 mg With Vinorelbine 25 mg/m^2 (Cohort 1)
Serious events: 2 serious events
Other events: 3 other events
Deaths: 0 deaths
Afatinib 40 mg With Vinorelbine 25 mg/m^2 (Cohort 2)
Serious events: 4 serious events
Other events: 5 other events
Deaths: 0 deaths
Afatinib 40 mg With Vinorelbine 20 mg/m^2 (Cohort 2a)
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Afatinib 40 mg With Vinorelbine 25 mg/m^2 (Cohort 3)
Serious events: 2 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Afatinib 20 mg With Vinorelbine 25 mg/m^2 (Cohort 1)
n=3 participants at risk
Afatinib 20 mg oral administration once a day with vinorelbine 25 mg/m\^2 intravenous injection weekly
|
Afatinib 40 mg With Vinorelbine 25 mg/m^2 (Cohort 2)
n=5 participants at risk
Afatinib 40 mg oral administration once a day with vinorelbine 25 mg/m\^2 intravenous injection weekly
|
Afatinib 40 mg With Vinorelbine 20 mg/m^2 (Cohort 2a)
n=3 participants at risk
Afatinib 40 mg oral administration once a day with vinorelbine 20 mg/m\^2 intravenous injection weekly
|
Afatinib 40 mg With Vinorelbine 25 mg/m^2 (Cohort 3)
n=6 participants at risk
Afatinib 40 mg oral administration once a day with vinorelbine 25 mg/m\^2 intravenous injection weekly; allowed for vinorelbine dose to be skipped for Common Toxicity Criteria for Adverse Effects (CTCAE) Grade 2 or worse neutropenia or thrombocytopenia
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
40.0%
2/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
16.7%
1/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Cardiac disorders
Cardiac tamponade
|
33.3%
1/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
General disorders
General physical health deterioration
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
16.7%
1/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
33.3%
1/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Infections and infestations
Bacteraemia
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
20.0%
1/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Infections and infestations
Biliary tract infection
|
33.3%
1/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
20.0%
1/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Infections and infestations
Hepatic infection
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
20.0%
1/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
20.0%
1/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Investigations
Amylase increased
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
20.0%
1/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Investigations
Lipase increased
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
20.0%
1/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Extradural neoplasm
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
16.7%
1/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant pleural effusion
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
16.7%
1/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
16.7%
1/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
16.7%
1/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
16.7%
1/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
Other adverse events
| Measure |
Afatinib 20 mg With Vinorelbine 25 mg/m^2 (Cohort 1)
n=3 participants at risk
Afatinib 20 mg oral administration once a day with vinorelbine 25 mg/m\^2 intravenous injection weekly
|
Afatinib 40 mg With Vinorelbine 25 mg/m^2 (Cohort 2)
n=5 participants at risk
Afatinib 40 mg oral administration once a day with vinorelbine 25 mg/m\^2 intravenous injection weekly
|
Afatinib 40 mg With Vinorelbine 20 mg/m^2 (Cohort 2a)
n=3 participants at risk
Afatinib 40 mg oral administration once a day with vinorelbine 20 mg/m\^2 intravenous injection weekly
|
Afatinib 40 mg With Vinorelbine 25 mg/m^2 (Cohort 3)
n=6 participants at risk
Afatinib 40 mg oral administration once a day with vinorelbine 25 mg/m\^2 intravenous injection weekly; allowed for vinorelbine dose to be skipped for Common Toxicity Criteria for Adverse Effects (CTCAE) Grade 2 or worse neutropenia or thrombocytopenia
|
|---|---|---|---|---|
|
Infections and infestations
Paronychia
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
20.0%
1/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
16.7%
1/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Infections and infestations
Pneumonia
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
16.7%
1/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
40.0%
2/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Investigations
Amylase increased
|
33.3%
1/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
20.0%
1/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
20.0%
1/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Investigations
Blood alkaline phosphatase increased
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
33.3%
1/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Investigations
Blood creatine phosphokinase increased
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
33.3%
1/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Investigations
Lipase increased
|
33.3%
1/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
20.0%
1/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Investigations
Weight decreased
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
40.0%
2/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
33.3%
1/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
33.3%
2/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Blood and lymphatic system disorders
Neutropenia
|
100.0%
3/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
100.0%
5/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
100.0%
3/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
100.0%
6/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
General disorders
Mucosal inflammation
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
40.0%
2/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
General disorders
Pyrexia
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
40.0%
2/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
33.3%
1/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
33.3%
2/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
16.7%
1/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
33.3%
1/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
33.3%
1/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
33.3%
2/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Infections and infestations
Device related infection
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
16.7%
1/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Infections and infestations
Nasopharyngitis
|
33.3%
1/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
16.7%
1/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Infections and infestations
Neutropenic infection
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
20.0%
1/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Eye disorders
Cataract
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
33.3%
1/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Infections and infestations
Cellulitis
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
16.7%
1/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Infections and infestations
Cystitis
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
16.7%
1/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Eye disorders
Conjunctivitis
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
20.0%
1/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Eye disorders
Keratitis
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
16.7%
1/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Eye disorders
Vitreous floaters
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
20.0%
1/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
20.0%
1/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
33.3%
1/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
16.7%
1/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Gastrointestinal disorders
Cheilitis
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
20.0%
1/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Gastrointestinal disorders
Constipation
|
33.3%
1/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Gastrointestinal disorders
Diarrhoea
|
66.7%
2/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
100.0%
5/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
100.0%
3/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
100.0%
6/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
80.0%
4/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Cardiac disorders
Supraventricular extrasystoles
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
20.0%
1/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
20.0%
1/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
20.0%
1/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
16.7%
1/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
20.0%
1/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
16.7%
1/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
16.7%
1/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Gastrointestinal disorders
Stomatitis
|
66.7%
2/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
20.0%
1/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
66.7%
2/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
100.0%
6/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
16.7%
1/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
General disorders
Fatigue
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
40.0%
2/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
16.7%
1/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
General disorders
Influenza like illness
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
33.3%
1/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
General disorders
Infusion site extravasation
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
33.3%
2/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
General disorders
Malaise
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
20.0%
1/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
33.3%
2/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Blood and lymphatic system disorders
Lymphopenia
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
40.0%
2/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Blood and lymphatic system disorders
Anaemia
|
33.3%
1/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
100.0%
5/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
100.0%
3/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
50.0%
3/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
16.7%
1/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Blood and lymphatic system disorders
Leukopenia
|
100.0%
3/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
100.0%
5/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
100.0%
3/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
100.0%
6/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
60.0%
3/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
33.3%
2/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Metabolism and nutrition disorders
Hyperamylasaemia
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
20.0%
1/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
20.0%
1/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
20.0%
1/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
33.3%
2/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
20.0%
1/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
33.3%
1/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
40.0%
2/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Nervous system disorders
Dizziness
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
16.7%
1/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
16.7%
1/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Nervous system disorders
Headache
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
20.0%
1/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Nervous system disorders
Hypoaesthesia
|
33.3%
1/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Nervous system disorders
Presyncope
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
20.0%
1/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Psychiatric disorders
Delirium
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
16.7%
1/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Psychiatric disorders
Insomnia
|
33.3%
1/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
20.0%
1/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Renal and urinary disorders
Renal impairment
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
16.7%
1/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
16.7%
1/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
66.7%
2/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
33.3%
1/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
16.7%
1/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
33.3%
1/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
16.7%
1/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Skin and subcutaneous tissue disorders
Acne
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
60.0%
3/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
16.7%
1/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
20.0%
1/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
16.7%
1/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
16.7%
1/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
33.3%
1/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
20.0%
1/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
33.3%
1/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
20.0%
1/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
16.7%
1/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
33.3%
1/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
20.0%
1/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
33.3%
1/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
33.3%
2/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
33.3%
1/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
20.0%
1/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
20.0%
1/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
100.0%
3/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
50.0%
3/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Skin and subcutaneous tissue disorders
Skin hyperpigmentation
|
33.3%
1/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
20.0%
1/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Skin and subcutaneous tissue disorders
Xeroderma
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
20.0%
1/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Vascular disorders
Flushing
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
16.7%
1/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Vascular disorders
Hypotension
|
33.3%
1/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Vascular disorders
Phlebitis
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
33.3%
1/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
|
Vascular disorders
Vasculitis
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
80.0%
4/5 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
0.00%
0/3 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
33.3%
2/6 • during the treatment period or up to 28 days after the completion of drug administration, up to 730 days
|
Additional Information
Boehringer Ingelheim Call Center
Boehringer Ingelheim Pharmaceuticals
Phone: 1-800-243-0127
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
- Publication restrictions are in place
Restriction type: OTHER