Trial Outcomes & Findings for BIBW 2992 as add-on to Gem/Cis in Advanced Biliary Tract Cancer (NCT NCT01679405)
NCT ID: NCT01679405
Last Updated: 2019-09-06
Results Overview
In part A the maximum tolerated dose (MTD) of BIBW 2992 administered continuously to the standard therapy of Gemcitabine / Cisplatin (Gem/Cis) (administered together on day 1 and 8 of a three-week cycle) will be evaluated in a 2 step dose escalation. Safety and toxicity will be evaluated as described and considered primary for part B of the study.
Recruitment status
TERMINATED
Study phase
PHASE1
Target enrollment
9 participants
Primary outcome timeframe
Treatment period: up to eight cycles (maximum 8 months). 12 months follow-up period.
Results posted on
2019-09-06
Participant Flow
Participant milestones
| Measure |
Dose Level 1
30 mg BIBW 2992, Gemcitabine (1.000 mg/m² BSA i.v.)/Cisplatin (25 mg/m² BSA i.v.)
|
Dose Level -1
30 mg BIBW 2992, Gemcitabine (800 mg/m² BSA i.v.)/Cisplatin (20 mg/m² BSA i.v.)
|
|---|---|---|
|
Overall Study
STARTED
|
3
|
6
|
|
Overall Study
COMPLETED
|
1
|
1
|
|
Overall Study
NOT COMPLETED
|
2
|
5
|
Reasons for withdrawal
| Measure |
Dose Level 1
30 mg BIBW 2992, Gemcitabine (1.000 mg/m² BSA i.v.)/Cisplatin (25 mg/m² BSA i.v.)
|
Dose Level -1
30 mg BIBW 2992, Gemcitabine (800 mg/m² BSA i.v.)/Cisplatin (20 mg/m² BSA i.v.)
|
|---|---|---|
|
Overall Study
Death
|
2
|
5
|
Baseline Characteristics
BIBW 2992 as add-on to Gem/Cis in Advanced Biliary Tract Cancer
Baseline characteristics by cohort
| Measure |
Dose Level 1
n=3 Participants
30 mg BIBW 2992, Gemcitabine (1.000 mg/m² BSA i.v.)/Cisplatin (25 mg/m² BSA i.v.)
|
Dose Level -1
n=6 Participants
30 mg BIBW 2992, Gemcitabine (800 mg/m² BSA i.v.)/Cisplatin (20 mg/m² BSA i.v.)
|
Total
n=9 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
62.00 years
STANDARD_DEVIATION 21.63 • n=93 Participants
|
60.17 years
STANDARD_DEVIATION 7.31 • n=4 Participants
|
60.78 years
STANDARD_DEVIATION 12.30 • n=27 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
4 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
5 Participants
n=27 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
White
|
3 Participants
n=93 Participants
|
6 Participants
n=4 Participants
|
9 Participants
n=27 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Region of Enrollment
Germany
|
3 participants
n=93 Participants
|
6 participants
n=4 Participants
|
9 participants
n=27 Participants
|
PRIMARY outcome
Timeframe: Treatment period: up to eight cycles (maximum 8 months). 12 months follow-up period.In part A the maximum tolerated dose (MTD) of BIBW 2992 administered continuously to the standard therapy of Gemcitabine / Cisplatin (Gem/Cis) (administered together on day 1 and 8 of a three-week cycle) will be evaluated in a 2 step dose escalation. Safety and toxicity will be evaluated as described and considered primary for part B of the study.
Outcome measures
| Measure |
Dose Level 1
n=3 Participants
30 mg BIBW 2992, Gemcitabine (1.000 mg/m² BSA i.v.)/Cisplatin (25 mg/m² BSA i.v.)
|
Dose Level -1
n=6 Participants
30 mg BIBW 2992, Gemcitabine (800 mg/m² BSA i.v.)/Cisplatin (20 mg/m² BSA i.v.)
|
|---|---|---|
|
Number of Adverse Events
|
2 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Treatment period: up to eight cycles (maximum 8 months). 12 months follow-up period.Median time to progress (according to RECIST 1.1 criteria) including the 95% confidence intervals were determined using Kaplan-Meier estimates. Time from start of treatment to first documentation of objective tumour progression. Deaths were censored at the time of death.
Outcome measures
| Measure |
Dose Level 1
n=3 Participants
30 mg BIBW 2992, Gemcitabine (1.000 mg/m² BSA i.v.)/Cisplatin (25 mg/m² BSA i.v.)
|
Dose Level -1
n=6 Participants
30 mg BIBW 2992, Gemcitabine (800 mg/m² BSA i.v.)/Cisplatin (20 mg/m² BSA i.v.)
|
|---|---|---|
|
Time to Progress (TTP)
|
159 days
Interval 134.0 to 184.0
|
NA days
Interval 49.0 to
Median and upper confidence limit could not be calculated, because of too few events.
|
SECONDARY outcome
Timeframe: Time from start of treatment to death due to any cause. Time to last observation will be used if a patient has not died and OS for the patient will be considered censored. Estimated time period: up to 76 weeksMedian overall survival time including the 95% confidence interval were determined using Kaplan-Meier estimates.
Outcome measures
| Measure |
Dose Level 1
n=3 Participants
30 mg BIBW 2992, Gemcitabine (1.000 mg/m² BSA i.v.)/Cisplatin (25 mg/m² BSA i.v.)
|
Dose Level -1
n=6 Participants
30 mg BIBW 2992, Gemcitabine (800 mg/m² BSA i.v.)/Cisplatin (20 mg/m² BSA i.v.)
|
|---|---|---|
|
Overall Survival (OS)
|
163 days
Interval 79.0 to
Upper confidence limit could not be calculated, because of too few events.
|
260 days
Interval 75.0 to
Upper confidence limit could not be calculated, because of too few events.
|
SECONDARY outcome
Timeframe: Treatment period: up to eight cycles (maximum 8 months).Population: For one patient, there was no CT assessment.
Response was assessed by means of RECIST 1.1 criteria for target lesions, non-target lesions and the appearance of new lesions. Objective response was defined as the CR, PR or SD at end of treatment
Outcome measures
| Measure |
Dose Level 1
n=2 Participants
30 mg BIBW 2992, Gemcitabine (1.000 mg/m² BSA i.v.)/Cisplatin (25 mg/m² BSA i.v.)
|
Dose Level -1
n=6 Participants
30 mg BIBW 2992, Gemcitabine (800 mg/m² BSA i.v.)/Cisplatin (20 mg/m² BSA i.v.)
|
|---|---|---|
|
Objective Response Rate
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Treatment period: up to eight cycles (maximum 8 months).Population: For one patient there was no CT assessment.
Tumor control rate is defined as the best tumour response (confirmed partial or complete response, stable disease) that is achieved until end of treatment according to Recist 1.1.
Outcome measures
| Measure |
Dose Level 1
n=2 Participants
30 mg BIBW 2992, Gemcitabine (1.000 mg/m² BSA i.v.)/Cisplatin (25 mg/m² BSA i.v.)
|
Dose Level -1
n=6 Participants
30 mg BIBW 2992, Gemcitabine (800 mg/m² BSA i.v.)/Cisplatin (20 mg/m² BSA i.v.)
|
|---|---|---|
|
Tumor Control Rate
|
0 Participants
|
4 Participants
|
Adverse Events
Dose Level 1
Serious events: 2 serious events
Other events: 3 other events
Deaths: 2 deaths
Dose Level -1
Serious events: 5 serious events
Other events: 6 other events
Deaths: 5 deaths
Serious adverse events
| Measure |
Dose Level 1
n=3 participants at risk
30 mg BIBW 2992, Gemcitabine (1.000 mg/m² BSA i.v.)/Cisplatin (25 mg/m² BSA i.v.)
|
Dose Level -1
n=6 participants at risk
30 mg BIBW 2992, Gemcitabine (800 mg/m² BSA i.v.)/Cisplatin (20 mg/m² BSA i.v.)
|
|---|---|---|
|
General disorders
Progression of disease (fatal)
|
33.3%
1/3 • Number of events 1
|
0.00%
0/6
|
|
Investigations
thrombocytopenia, anaemia, hypokaliemia
|
33.3%
1/3 • Number of events 1
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
worsening of pleural effusion
|
33.3%
1/3 • Number of events 1
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
pulmonary embolism
|
0.00%
0/3
|
16.7%
1/6 • Number of events 1
|
|
Hepatobiliary disorders
liver failure
|
0.00%
0/3
|
16.7%
1/6 • Number of events 1
|
|
Gastrointestinal disorders
diarrhea
|
0.00%
0/3
|
16.7%
1/6 • Number of events 1
|
|
Gastrointestinal disorders
diarrhea, hypokaliemia
|
0.00%
0/3
|
16.7%
1/6 • Number of events 1
|
|
Infections and infestations
sepsis, chronic kidney disease (worsening), platelet count decreased, worsening of anemia, diarrhea
|
0.00%
0/3
|
16.7%
1/6 • Number of events 1
|
|
Infections and infestations
Infection unknown origin, platelet count decreased
|
0.00%
0/3
|
16.7%
1/6 • Number of events 1
|
|
Infections and infestations
"infection unknown origin, worsening of chronic kidney disease, platelet count decreased, leukocytop
|
0.00%
0/3
|
16.7%
1/6 • Number of events 1
|
|
Infections and infestations
Biliary tract infection
|
0.00%
0/3
|
16.7%
1/6 • Number of events 1
|
|
Infections and infestations
infection, unknown origin, pulmonary embolism both sides, deep vein thrombosis both leg
|
0.00%
0/3
|
16.7%
1/6 • Number of events 1
|
Other adverse events
| Measure |
Dose Level 1
n=3 participants at risk
30 mg BIBW 2992, Gemcitabine (1.000 mg/m² BSA i.v.)/Cisplatin (25 mg/m² BSA i.v.)
|
Dose Level -1
n=6 participants at risk
30 mg BIBW 2992, Gemcitabine (800 mg/m² BSA i.v.)/Cisplatin (20 mg/m² BSA i.v.)
|
|---|---|---|
|
General disorders
fatigue
|
100.0%
3/3 • Number of events 11
|
100.0%
6/6 • Number of events 19
|
|
Gastrointestinal disorders
nausea
|
100.0%
3/3 • Number of events 5
|
83.3%
5/6 • Number of events 9
|
|
Gastrointestinal disorders
diarrhoea
|
66.7%
2/3 • Number of events 4
|
83.3%
5/6 • Number of events 25
|
|
Skin and subcutaneous tissue disorders
rash
|
100.0%
3/3 • Number of events 7
|
66.7%
4/6 • Number of events 10
|
|
Gastrointestinal disorders
stomatitis
|
100.0%
3/3 • Number of events 6
|
66.7%
4/6 • Number of events 8
|
|
Blood and lymphatic system disorders
anemia
|
100.0%
3/3 • Number of events 7
|
66.7%
4/6 • Number of events 8
|
|
Investigations
weight loss
|
33.3%
1/3 • Number of events 2
|
100.0%
6/6 • Number of events 9
|
|
Respiratory, thoracic and mediastinal disorders
epistaxis
|
66.7%
2/3 • Number of events 3
|
33.3%
2/6 • Number of events 2
|
|
Investigations
neutropenia
|
66.7%
2/3 • Number of events 11
|
50.0%
3/6 • Number of events 9
|
|
Investigations
thrombocytopenia
|
100.0%
3/3 • Number of events 17
|
50.0%
3/6 • Number of events 20
|
|
Metabolism and nutrition disorders
hypokalemia
|
66.7%
2/3 • Number of events 4
|
50.0%
3/6 • Number of events 6
|
|
Nervous system disorders
paresthesia
|
33.3%
1/3 • Number of events 1
|
66.7%
4/6 • Number of events 9
|
|
Infections and infestations
paronychia
|
33.3%
1/3 • Number of events 1
|
66.7%
4/6 • Number of events 4
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place