Trial Outcomes & Findings for Efficacy and Safety of Nilotinib (AMN107) Compared With Current Treatment Options in Patients With GIST Who Have Failed Both Imatinib and Sunitinib (NCT NCT00471328)
NCT ID: NCT00471328
Last Updated: 2012-06-12
Results Overview
Progression-free survival (PFS) is the time from date of randomization to the date of first documented progression or death due to any cause. If a participant has not had an event, progression-free survival is censored at the time of last adequate tumor assessment. Progression is defined according to Modified Response Evaluation Criteria in Solid Tumors (modified RECIST) criteria as at least a 20% increase in the sum of the longest diameter of target lesions, worsening of the non-target lesions or the appearance of one or more new lesions.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
248 participants
Primary outcome timeframe
Up to 16 months
Results posted on
2012-06-12
Participant Flow
Patients ongoing on treatment at primary analysis had option to enter extension. Patients in control arm were allowed cross over to Nilotinib arm at disease progression and considered as part of extension. Patients entering the extension part on control arm were permitted to cross over to the nilotinib only upon documented disease progression.
Participant milestones
| Measure |
Nilotinib
400 mg was taken orally twice daily in core and extension phase of the study
|
Control/Cross Over to Nilotinib
In core study phase, patients in this arm received Best Supportive Care (BSC) with or without imatinib or sunitinib at the last tolerated dose or at the investigator's choice until documented disease progression followed by cross-over to nilotinib arm.
Patients entering the extension study on this control arm were permitted to cross over to nilotinib arm only upon documented disease progression.
|
|---|---|---|
|
Core Phase
STARTED
|
165
|
83
|
|
Core Phase
Crossover to Nilotinib:Started Extension
|
0
|
53
|
|
Core Phase
COMPLETED
|
58
|
16
|
|
Core Phase
NOT COMPLETED
|
107
|
67
|
|
Extension Phase
STARTED
|
41
|
67
|
|
Extension Phase
Started:CrossOver Before PrimaryAnalysis
|
0
|
53
|
|
Extension Phase
Started:CrossOver After PrimaryAnalysis
|
0
|
4
|
|
Extension Phase
Started:CrossOver During Extension
|
0
|
10
|
|
Extension Phase
COMPLETED
|
0
|
0
|
|
Extension Phase
NOT COMPLETED
|
41
|
67
|
Reasons for withdrawal
| Measure |
Nilotinib
400 mg was taken orally twice daily in core and extension phase of the study
|
Control/Cross Over to Nilotinib
In core study phase, patients in this arm received Best Supportive Care (BSC) with or without imatinib or sunitinib at the last tolerated dose or at the investigator's choice until documented disease progression followed by cross-over to nilotinib arm.
Patients entering the extension study on this control arm were permitted to cross over to nilotinib arm only upon documented disease progression.
|
|---|---|---|
|
Core Phase
Adverse Event
|
18
|
6
|
|
Core Phase
Death
|
8
|
4
|
|
Core Phase
Withdrawal by Subject
|
2
|
2
|
|
Core Phase
Abnormal laboratory value
|
1
|
0
|
|
Core Phase
Disease Progression
|
78
|
53
|
|
Core Phase
Administrative Problem
|
0
|
1
|
|
Core Phase
Protocol Deviation
|
0
|
1
|
|
Extension Phase
Adverse Event
|
3
|
12
|
|
Extension Phase
Withdrawal by Subject
|
0
|
2
|
|
Extension Phase
Death
|
1
|
7
|
|
Extension Phase
Protocol Deviation
|
3
|
1
|
|
Extension Phase
Treatment duration as per protocol
|
0
|
1
|
|
Extension Phase
Disease Progression
|
32
|
44
|
|
Extension Phase
New cancer Therapy
|
1
|
0
|
|
Extension Phase
Administrative Problem
|
1
|
0
|
Baseline Characteristics
Efficacy and Safety of Nilotinib (AMN107) Compared With Current Treatment Options in Patients With GIST Who Have Failed Both Imatinib and Sunitinib
Baseline characteristics by cohort
| Measure |
Nilotinib
n=165 Participants
400 mg was taken orally twice daily in core and extension phase of the study
|
Control/Cross Over to Nilotinib
n=83 Participants
In core study phase, patients in this arm received Best Supportive Care (BSC) with or without imatinib or sunitinib at the last tolerated dose or at the investigator's choice until documented disease progression followed by cross-over to nilotinib arm.
Patients entering the extension study on this control arm were permitted to cross over to nilotinib arm only upon documented disease progression.
|
Total
n=248 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
118 Participants
n=5 Participants
|
57 Participants
n=7 Participants
|
175 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
47 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
73 Participants
n=5 Participants
|
|
Age Continuous
|
57.4 years
STANDARD_DEVIATION 12.69 • n=5 Participants
|
58.6 years
STANDARD_DEVIATION 10.57 • n=7 Participants
|
57.8 years
STANDARD_DEVIATION 12.01 • n=5 Participants
|
|
Sex: Female, Male
Female
|
64 Participants
n=5 Participants
|
36 Participants
n=7 Participants
|
100 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
101 Participants
n=5 Participants
|
47 Participants
n=7 Participants
|
148 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
21 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
32 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
134 Participants
n=5 Participants
|
67 Participants
n=7 Participants
|
201 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
6 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 16 monthsPopulation: The intent to treat (ITT) population was defined as all randomized patients and was used as the primary efficacy population.
Progression-free survival (PFS) is the time from date of randomization to the date of first documented progression or death due to any cause. If a participant has not had an event, progression-free survival is censored at the time of last adequate tumor assessment. Progression is defined according to Modified Response Evaluation Criteria in Solid Tumors (modified RECIST) criteria as at least a 20% increase in the sum of the longest diameter of target lesions, worsening of the non-target lesions or the appearance of one or more new lesions.
Outcome measures
| Measure |
Nilotinib
n=165 Participants
400 mg was taken orally twice daily in core and extension phase of the study
|
Control/Cross Over to Nilotinib
n=83 Participants
In core study phase, patients in this arm received Best Supportive Care (BSC) with or without imatinib or sunitinib at the last tolerated dose or at the investigator's choice until documented disease progression followed by cross-over to nilotinib arm.
Patients entering the extension study on this control arm were permitted to cross over to nilotinib arm only upon documented disease progression.
|
|---|---|---|
|
Progression-free Survival (PFS) From Central Radiology Review Based on Primary Analysis (Data Cut-off: June, 2008)
|
109.0 days
Interval 61.0 to 113.0
|
111.0 days
Interval 60.0 to 116.0
|
PRIMARY outcome
Timeframe: Up to 34 monthsPopulation: Treatment Crossover Analysis Set: All patients who crossed over from control arm to nilotinib after completing the Core study or during the Extension study after disease progression.
PFS is defined as the time from the first date of cross-over to nilotinib therapy from the control arm to the date of the first observation of documented disease progression. Tumor assessment was based on the local investigator's measurement using Modified Response Evaluation Criteria in Solid Tumors (modified RECIST) criteria. Progression is defined according to modified RECIST criteria as at least a 20% increase in the sum of the longest diameter of target lesions, worsening of the non-target lesions or the appearance of one or more new lesions.
Outcome measures
| Measure |
Nilotinib
n=67 Participants
400 mg was taken orally twice daily in core and extension phase of the study
|
Control/Cross Over to Nilotinib
In core study phase, patients in this arm received Best Supportive Care (BSC) with or without imatinib or sunitinib at the last tolerated dose or at the investigator's choice until documented disease progression followed by cross-over to nilotinib arm.
Patients entering the extension study on this control arm were permitted to cross over to nilotinib arm only upon documented disease progression.
|
|---|---|---|
|
Progression-free Survival (PFS) From Local Investigator's Assessment Based on Treatment Crossover Analysis Set
|
84 days
Interval 56.0 to 109.0
|
—
|
SECONDARY outcome
Timeframe: Up to 16 monthsPopulation: The intent to treat (ITT) population was defined as all randomized participants and was used as the primary efficacy population.
Overall survival (OS) is defined as the time from date of randomization to date of death due to any cause. If a participant is not known to have died, survival will be censored at the date of last contact.
Outcome measures
| Measure |
Nilotinib
n=165 Participants
400 mg was taken orally twice daily in core and extension phase of the study
|
Control/Cross Over to Nilotinib
n=83 Participants
In core study phase, patients in this arm received Best Supportive Care (BSC) with or without imatinib or sunitinib at the last tolerated dose or at the investigator's choice until documented disease progression followed by cross-over to nilotinib arm.
Patients entering the extension study on this control arm were permitted to cross over to nilotinib arm only upon documented disease progression.
|
|---|---|---|
|
Overall Survival Based on Primary Analysis (Data Cut-off:June, 2008)
|
332.0 days
Interval 246.0 to
The upper limit of CI was not computable due to insufficient number of events.
|
280.0 days
Interval 240.0 to 372.0
|
SECONDARY outcome
Timeframe: Up to 50 months (including core, extension and follow up period)Population: Core Full Analysis Set (Core FAS): included all randomized patients included in the Core study. Analyses based on Core FAS does not account for treatment crossover i.e.pooling all data both before and after crossover. This analysis set was used to conduct an overall survival analysis.
Overall survival (OS) is defined as the time from date of randomization to date of death due to any cause. If a participant is not known to have died, survival will be censored at the date of last contact. This analysis included both Core and Extension data as well as survival follow up data.
Outcome measures
| Measure |
Nilotinib
n=165 Participants
400 mg was taken orally twice daily in core and extension phase of the study
|
Control/Cross Over to Nilotinib
n=83 Participants
In core study phase, patients in this arm received Best Supportive Care (BSC) with or without imatinib or sunitinib at the last tolerated dose or at the investigator's choice until documented disease progression followed by cross-over to nilotinib arm.
Patients entering the extension study on this control arm were permitted to cross over to nilotinib arm only upon documented disease progression.
|
|---|---|---|
|
Overall Survival During Core and Extension Phases of the Study
|
361 days
Interval 265.0 to 425.0
|
300 days
Interval 246.0 to 386.0
|
SECONDARY outcome
Timeframe: Up to 34 monthsPopulation: Treatment Crossover Analysis Set: All patients who crossed over from control arm to nilotinib after completing the Core study or during the Extension study after disease progression.
For patients who crossed-over to nilotinib from the control arm, the overall survival was the time from the first dose date of nilotinib after switching from control arm to the date of death due to any cause. If death was not observed, the OS was censored at the latest date the patient was known to be alive.
Outcome measures
| Measure |
Nilotinib
n=67 Participants
400 mg was taken orally twice daily in core and extension phase of the study
|
Control/Cross Over to Nilotinib
In core study phase, patients in this arm received Best Supportive Care (BSC) with or without imatinib or sunitinib at the last tolerated dose or at the investigator's choice until documented disease progression followed by cross-over to nilotinib arm.
Patients entering the extension study on this control arm were permitted to cross over to nilotinib arm only upon documented disease progression.
|
|---|---|---|
|
Overall Survival for Treatment Crossover Analysis Set
|
231 days
Interval 196.0 to 327.0
|
—
|
SECONDARY outcome
Timeframe: Up to 16 monthsPopulation: The intent to treat (ITT) population was defined as all randomized patients and was used as the primary efficacy population.
The best overall response is the best response recorded from randomization until disease progression. The CR/PR must be confirmed by at least two determinations at least 4 weeks apart before progression. Using modified RECIST criteria, a Complete Response is defined as disappearance of all lesions, and a Partial Response is defined as either 1) at least a 30% decrease in the sum of the longest diameter of target lesions and no new lesions or progression of non-target lesions or 2) disappearance of all target lesions but persistence of one or more non-target lesion(s).
Outcome measures
| Measure |
Nilotinib
n=165 Participants
400 mg was taken orally twice daily in core and extension phase of the study
|
Control/Cross Over to Nilotinib
n=83 Participants
In core study phase, patients in this arm received Best Supportive Care (BSC) with or without imatinib or sunitinib at the last tolerated dose or at the investigator's choice until documented disease progression followed by cross-over to nilotinib arm.
Patients entering the extension study on this control arm were permitted to cross over to nilotinib arm only upon documented disease progression.
|
|---|---|---|
|
Number of Responders With Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR) From Central Radiology Review During Primary Analysis (Data Cut-off: June, 2008)
|
1 Participants
Interval 0.0 to 3.3
|
0 Participants
Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: Up to 34 monthsPopulation: Treatment Crossover Analysis Set: All patients who crossed over from control arm to nilotinib after completing the Core study or during the Extension study after disease progression.
The best overall response (CR/PR) must be confirmed by at least two determinations at least 4 weeks apart before progression. Using modified RECIST criteria, a Complete Response is defined as disappearance of all lesions, and a Partial Response is defined as either 1) at least a 30% decrease in the sum of the longest diameter of target lesions and no new lesions or progression of non-target lesions or 2) disappearance of all target lesions but persistence of one or more non-target lesion(s).
Outcome measures
| Measure |
Nilotinib
n=67 Participants
400 mg was taken orally twice daily in core and extension phase of the study
|
Control/Cross Over to Nilotinib
In core study phase, patients in this arm received Best Supportive Care (BSC) with or without imatinib or sunitinib at the last tolerated dose or at the investigator's choice until documented disease progression followed by cross-over to nilotinib arm.
Patients entering the extension study on this control arm were permitted to cross over to nilotinib arm only upon documented disease progression.
|
|---|---|---|
|
Number of Responders With Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR) From Local Investigator's Assessment Based on Treatment Crossover Analysis Set
|
1 Participants
Interval 0.0 to 8.0
|
—
|
SECONDARY outcome
Timeframe: Up to 16 monthsPopulation: The intent to treat (ITT) population was defined as all randomized patients and was used as the primary efficacy population.
The overall clinical benefit includes the best overall responses of CR, PR, or SD. The best overall responses of CR/PR must be confirmed by at least two determinations at least 4 weeks apart before progression. The best overall response of SD must have at least one SD (or better) at least 6 weeks (or 6 months or 12 months as applicable) after randomization but before progression.
Outcome measures
| Measure |
Nilotinib
n=165 Participants
400 mg was taken orally twice daily in core and extension phase of the study
|
Control/Cross Over to Nilotinib
n=83 Participants
In core study phase, patients in this arm received Best Supportive Care (BSC) with or without imatinib or sunitinib at the last tolerated dose or at the investigator's choice until documented disease progression followed by cross-over to nilotinib arm.
Patients entering the extension study on this control arm were permitted to cross over to nilotinib arm only upon documented disease progression.
|
|---|---|---|
|
Overall Clinical Benefit (Complete Response [CR]/Partial Response [PR] or Stable Disease [SD]) From Central Radiology Review Based on Primary Analysis (Data Cut-off: June, 2008)
CR/PR/SD
|
52.7 Percentage of Participants
Interval 44.8 to 60.5
|
44.6 Percentage of Participants
Interval 33.7 to 55.9
|
|
Overall Clinical Benefit (Complete Response [CR]/Partial Response [PR] or Stable Disease [SD]) From Central Radiology Review Based on Primary Analysis (Data Cut-off: June, 2008)
CR/PR/SD lasting > 6 months
|
7.3 Percentage of Participants
Interval 3.8 to 12.4
|
1.2 Percentage of Participants
Interval 0.0 to 6.5
|
|
Overall Clinical Benefit (Complete Response [CR]/Partial Response [PR] or Stable Disease [SD]) From Central Radiology Review Based on Primary Analysis (Data Cut-off: June, 2008)
CR/PR/SD lasting > 12 months
|
0.6 Percentage of Participants
Interval 0.0 to 3.3
|
0 Percentage of Participants
Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: Up to 34 monthsPopulation: Treatment Crossover Analysis Set: All patients who crossed over from control arm to nilotinib after completing the Core study or during the Extension study after disease progression.
The overall clinical benefit includes the best overall responses of CR, PR, or SD. The best overall responses of CR/PR must be confirmed by at least two determinations at least 4 weeks apart before progression. The best overall response of SD must have at least one SD (or better) at least 6 weeks (or 6 months or 12 months as applicable) after randomization but before progression.
Outcome measures
| Measure |
Nilotinib
n=67 Participants
400 mg was taken orally twice daily in core and extension phase of the study
|
Control/Cross Over to Nilotinib
In core study phase, patients in this arm received Best Supportive Care (BSC) with or without imatinib or sunitinib at the last tolerated dose or at the investigator's choice until documented disease progression followed by cross-over to nilotinib arm.
Patients entering the extension study on this control arm were permitted to cross over to nilotinib arm only upon documented disease progression.
|
|---|---|---|
|
Overall Clinical Benefit (Complete Response [CR]/Partial Response [PR] or Stable Disease [SD]) From Local Investigator's Assessment Based on Treatment Crossover Analysis Set
CR/PR/SD
|
37.3 Percentage of Participants
Interval 25.8 to 50.0
|
—
|
|
Overall Clinical Benefit (Complete Response [CR]/Partial Response [PR] or Stable Disease [SD]) From Local Investigator's Assessment Based on Treatment Crossover Analysis Set
CR/PR/SD lasting > 6 months
|
7.5 Percentage of Participants
Interval 2.5 to 16.6
|
—
|
|
Overall Clinical Benefit (Complete Response [CR]/Partial Response [PR] or Stable Disease [SD]) From Local Investigator's Assessment Based on Treatment Crossover Analysis Set
CR/PR/SD lasting > 12 months
|
6.0 Percentage of Participants
Interval 1.7 to 14.6
|
—
|
Adverse Events
Nilotinib(Core +Extension)
Serious events: 81 serious events
Other events: 159 other events
Deaths: 0 deaths
Control(Core + Extension)
Serious events: 27 serious events
Other events: 73 other events
Deaths: 0 deaths
Crossover Nilotinib Therapy
Serious events: 32 serious events
Other events: 58 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Nilotinib(Core +Extension)
n=165 participants at risk
Patients randomized to 400 mg Nilotinib which was taken orally twice daily. The safety is assessed using these patient's data from both core and extension phase of the study.
|
Control(Core + Extension)
n=83 participants at risk
Patients randomized to control arm, Best Supportive Care (BSC) with or without imatinib or sunitinib at the last tolerated dose before the study or at the dose of the investigator's choice. The safety is assessed using these patient's data from both core and extension phase of the study.
|
Crossover Nilotinib Therapy
n=67 participants at risk
All patients who crossed over from control arm to nilotinib after completing the Core study or during the Extension study after disease progression were included in safety assessment.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
3.6%
6/165
|
8.4%
7/83
|
7.5%
5/67
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Cardiac disorders
Angina pectoris
|
1.2%
2/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Cardiac disorders
Cardiac arrest
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Cardiac disorders
Cyanosis
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/165
|
1.2%
1/83
|
0.00%
0/67
|
|
Cardiac disorders
Sinus bradycardia
|
1.2%
2/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Congenital, familial and genetic disorders
Spinocerebellar ataxia
|
0.00%
0/165
|
0.00%
0/83
|
1.5%
1/67
|
|
Endocrine disorders
Hypothyroidism
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/165
|
1.2%
1/83
|
0.00%
0/67
|
|
Gastrointestinal disorders
Abdominal distension
|
0.61%
1/165
|
0.00%
0/83
|
1.5%
1/67
|
|
Gastrointestinal disorders
Abdominal pain
|
12.7%
21/165
|
6.0%
5/83
|
4.5%
3/67
|
|
Gastrointestinal disorders
Abdominal pain lower
|
0.00%
0/165
|
1.2%
1/83
|
0.00%
0/67
|
|
Gastrointestinal disorders
Abdominal pain upper
|
1.2%
2/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Gastrointestinal disorders
Ascites
|
1.2%
2/165
|
2.4%
2/83
|
0.00%
0/67
|
|
Gastrointestinal disorders
Constipation
|
0.61%
1/165
|
0.00%
0/83
|
3.0%
2/67
|
|
Gastrointestinal disorders
Diarrhoea
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Gastrointestinal disorders
Duodenal ulcer
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Gastrointestinal disorders
Enteritis
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
1.8%
3/165
|
2.4%
2/83
|
3.0%
2/67
|
|
Gastrointestinal disorders
Gastrointestinal motility disorder
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Gastrointestinal disorders
Haematemesis
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Gastrointestinal disorders
Haematochezia
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Gastrointestinal disorders
Ileus
|
1.2%
2/165
|
0.00%
0/83
|
1.5%
1/67
|
|
Gastrointestinal disorders
Intestinal obstruction
|
1.8%
3/165
|
2.4%
2/83
|
1.5%
1/67
|
|
Gastrointestinal disorders
Lower gastrointestinal haemorrhage
|
0.00%
0/165
|
0.00%
0/83
|
1.5%
1/67
|
|
Gastrointestinal disorders
Mechanical ileus
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Gastrointestinal disorders
Melaena
|
1.2%
2/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Gastrointestinal disorders
Nausea
|
1.8%
3/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Gastrointestinal disorders
Obstruction gastric
|
0.00%
0/165
|
1.2%
1/83
|
0.00%
0/67
|
|
Gastrointestinal disorders
Oesophageal ulcer
|
0.00%
0/165
|
1.2%
1/83
|
0.00%
0/67
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Gastrointestinal disorders
Subileus
|
1.8%
3/165
|
1.2%
1/83
|
0.00%
0/67
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.00%
0/165
|
0.00%
0/83
|
3.0%
2/67
|
|
Gastrointestinal disorders
Vomiting
|
5.5%
9/165
|
1.2%
1/83
|
1.5%
1/67
|
|
General disorders
Asthenia
|
0.00%
0/165
|
1.2%
1/83
|
1.5%
1/67
|
|
General disorders
Chest pain
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
General disorders
Fatigue
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
General disorders
General physical health deterioration
|
9.7%
16/165
|
3.6%
3/83
|
14.9%
10/67
|
|
General disorders
Generalised oedema
|
0.00%
0/165
|
1.2%
1/83
|
0.00%
0/67
|
|
General disorders
Hyperpyrexia
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
General disorders
Multi-organ failure
|
0.00%
0/165
|
1.2%
1/83
|
1.5%
1/67
|
|
General disorders
Oedema peripheral
|
0.00%
0/165
|
0.00%
0/83
|
4.5%
3/67
|
|
General disorders
Pain
|
0.00%
0/165
|
1.2%
1/83
|
0.00%
0/67
|
|
General disorders
Performance status decreased
|
0.00%
0/165
|
0.00%
0/83
|
1.5%
1/67
|
|
General disorders
Pyrexia
|
3.0%
5/165
|
2.4%
2/83
|
1.5%
1/67
|
|
Hepatobiliary disorders
Cholestasis
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Hepatobiliary disorders
Hepatic failure
|
0.00%
0/165
|
1.2%
1/83
|
0.00%
0/67
|
|
Hepatobiliary disorders
Hepatomegaly
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Hepatobiliary disorders
Hepatorenal failure
|
0.00%
0/165
|
0.00%
0/83
|
1.5%
1/67
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Hepatobiliary disorders
Portal vein thrombosis
|
0.00%
0/165
|
0.00%
0/83
|
1.5%
1/67
|
|
Infections and infestations
Abdominal infection
|
0.00%
0/165
|
0.00%
0/83
|
1.5%
1/67
|
|
Infections and infestations
Alpha haemolytic streptococcal infection
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Infections and infestations
Bacteraemia
|
0.61%
1/165
|
1.2%
1/83
|
0.00%
0/67
|
|
Infections and infestations
Bacterial sepsis
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Infections and infestations
Empyema
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Infections and infestations
Escherichia infection
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Infections and infestations
Fungaemia
|
0.00%
0/165
|
0.00%
0/83
|
1.5%
1/67
|
|
Infections and infestations
Klebsiella sepsis
|
0.00%
0/165
|
1.2%
1/83
|
0.00%
0/67
|
|
Infections and infestations
Perihepatic abscess
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Infections and infestations
Pneumonia
|
1.2%
2/165
|
1.2%
1/83
|
3.0%
2/67
|
|
Infections and infestations
Pneumonia haemophilus
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Infections and infestations
Pyelonephritis acute
|
0.00%
0/165
|
0.00%
0/83
|
1.5%
1/67
|
|
Infections and infestations
Sepsis
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Infections and infestations
Septic shock
|
0.61%
1/165
|
1.2%
1/83
|
0.00%
0/67
|
|
Infections and infestations
Staphylococcal infection
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/165
|
0.00%
0/83
|
1.5%
1/67
|
|
Injury, poisoning and procedural complications
Overdose
|
0.00%
0/165
|
1.2%
1/83
|
0.00%
0/67
|
|
Investigations
Blood creatinine increased
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Investigations
Haemoglobin decreased
|
0.00%
0/165
|
0.00%
0/83
|
1.5%
1/67
|
|
Investigations
Weight decreased
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Metabolism and nutrition disorders
Decreased appetite
|
1.2%
2/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Metabolism and nutrition disorders
Dehydration
|
1.2%
2/165
|
1.2%
1/83
|
1.5%
1/67
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.61%
1/165
|
0.00%
0/83
|
1.5%
1/67
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
0.00%
0/165
|
0.00%
0/83
|
1.5%
1/67
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Metabolism and nutrition disorders
Hypovolaemia
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Metabolism and nutrition disorders
Malnutrition
|
0.00%
0/165
|
1.2%
1/83
|
0.00%
0/67
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.8%
3/165
|
1.2%
1/83
|
1.5%
1/67
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Brain neoplasm
|
0.00%
0/165
|
0.00%
0/83
|
1.5%
1/67
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Infected neoplasm
|
1.2%
2/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to liver
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm malignant
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm progression
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rectal cancer
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour compression
|
0.00%
0/165
|
0.00%
0/83
|
1.5%
1/67
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour haemorrhage
|
0.61%
1/165
|
0.00%
0/83
|
1.5%
1/67
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
0.61%
1/165
|
1.2%
1/83
|
0.00%
0/67
|
|
Nervous system disorders
Cerebrovascular accident
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Nervous system disorders
Coma
|
0.00%
0/165
|
0.00%
0/83
|
1.5%
1/67
|
|
Nervous system disorders
Convulsion
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Nervous system disorders
Depressed level of consciousness
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Nervous system disorders
Headache
|
0.00%
0/165
|
1.2%
1/83
|
0.00%
0/67
|
|
Nervous system disorders
Hepatic encephalopathy
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Nervous system disorders
Ischaemic stroke
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Nervous system disorders
Metabolic encephalopathy
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Nervous system disorders
Nystagmus
|
0.00%
0/165
|
0.00%
0/83
|
1.5%
1/67
|
|
Renal and urinary disorders
Haematuria
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Renal and urinary disorders
Hydronephrosis
|
0.00%
0/165
|
0.00%
0/83
|
1.5%
1/67
|
|
Renal and urinary disorders
Renal failure acute
|
1.2%
2/165
|
0.00%
0/83
|
3.0%
2/67
|
|
Renal and urinary disorders
Urinary retention
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Reproductive system and breast disorders
Pelvic pain
|
0.00%
0/165
|
1.2%
1/83
|
0.00%
0/67
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
2.4%
4/165
|
1.2%
1/83
|
6.0%
4/67
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Respiratory, thoracic and mediastinal disorders
Lung disorder
|
0.00%
0/165
|
1.2%
1/83
|
0.00%
0/67
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.61%
1/165
|
2.4%
2/83
|
1.5%
1/67
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
1.8%
3/165
|
2.4%
2/83
|
3.0%
2/67
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/165
|
1.2%
1/83
|
0.00%
0/67
|
|
Vascular disorders
Hypotension
|
1.2%
2/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Vascular disorders
Inferior vena caval occlusion
|
0.00%
0/165
|
0.00%
0/83
|
1.5%
1/67
|
|
Vascular disorders
Intra-abdominal haemorrhage
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
|
Vascular disorders
Venous thrombosis limb
|
0.61%
1/165
|
0.00%
0/83
|
0.00%
0/67
|
Other adverse events
| Measure |
Nilotinib(Core +Extension)
n=165 participants at risk
Patients randomized to 400 mg Nilotinib which was taken orally twice daily. The safety is assessed using these patient's data from both core and extension phase of the study.
|
Control(Core + Extension)
n=83 participants at risk
Patients randomized to control arm, Best Supportive Care (BSC) with or without imatinib or sunitinib at the last tolerated dose before the study or at the dose of the investigator's choice. The safety is assessed using these patient's data from both core and extension phase of the study.
|
Crossover Nilotinib Therapy
n=67 participants at risk
All patients who crossed over from control arm to nilotinib after completing the Core study or during the Extension study after disease progression were included in safety assessment.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
23.6%
39/165
|
20.5%
17/83
|
17.9%
12/67
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.61%
1/165
|
8.4%
7/83
|
0.00%
0/67
|
|
Eye disorders
Eyelid oedema
|
1.8%
3/165
|
8.4%
7/83
|
0.00%
0/67
|
|
Gastrointestinal disorders
Abdominal distension
|
10.3%
17/165
|
7.2%
6/83
|
7.5%
5/67
|
|
Gastrointestinal disorders
Abdominal pain
|
37.0%
61/165
|
22.9%
19/83
|
19.4%
13/67
|
|
Gastrointestinal disorders
Abdominal pain lower
|
1.8%
3/165
|
3.6%
3/83
|
6.0%
4/67
|
|
Gastrointestinal disorders
Abdominal pain upper
|
12.7%
21/165
|
7.2%
6/83
|
11.9%
8/67
|
|
Gastrointestinal disorders
Ascites
|
1.8%
3/165
|
6.0%
5/83
|
4.5%
3/67
|
|
Gastrointestinal disorders
Constipation
|
24.8%
41/165
|
10.8%
9/83
|
14.9%
10/67
|
|
Gastrointestinal disorders
Diarrhoea
|
17.0%
28/165
|
24.1%
20/83
|
7.5%
5/67
|
|
Gastrointestinal disorders
Dyspepsia
|
7.9%
13/165
|
7.2%
6/83
|
1.5%
1/67
|
|
Gastrointestinal disorders
Nausea
|
30.9%
51/165
|
39.8%
33/83
|
19.4%
13/67
|
|
Gastrointestinal disorders
Stomatitis
|
7.9%
13/165
|
4.8%
4/83
|
1.5%
1/67
|
|
Gastrointestinal disorders
Vomiting
|
20.0%
33/165
|
30.1%
25/83
|
20.9%
14/67
|
|
General disorders
Asthenia
|
27.9%
46/165
|
7.2%
6/83
|
13.4%
9/67
|
|
General disorders
Fatigue
|
27.9%
46/165
|
18.1%
15/83
|
17.9%
12/67
|
|
General disorders
Oedema peripheral
|
18.2%
30/165
|
31.3%
26/83
|
19.4%
13/67
|
|
General disorders
Pyrexia
|
18.8%
31/165
|
8.4%
7/83
|
11.9%
8/67
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
8.5%
14/165
|
1.2%
1/83
|
6.0%
4/67
|
|
Investigations
Alanine aminotransferase increased
|
8.5%
14/165
|
1.2%
1/83
|
0.00%
0/67
|
|
Investigations
Aspartate aminotransferase increased
|
7.3%
12/165
|
7.2%
6/83
|
0.00%
0/67
|
|
Investigations
Blood alkaline phosphatase increased
|
9.1%
15/165
|
4.8%
4/83
|
1.5%
1/67
|
|
Investigations
Lipase increased
|
6.7%
11/165
|
0.00%
0/83
|
1.5%
1/67
|
|
Investigations
Weight decreased
|
20.6%
34/165
|
8.4%
7/83
|
29.9%
20/67
|
|
Metabolism and nutrition disorders
Decreased appetite
|
28.5%
47/165
|
21.7%
18/83
|
23.9%
16/67
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
6.1%
10/165
|
2.4%
2/83
|
3.0%
2/67
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
4.8%
8/165
|
3.6%
3/83
|
6.0%
4/67
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
4.2%
7/165
|
6.0%
5/83
|
3.0%
2/67
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
5.5%
9/165
|
3.6%
3/83
|
6.0%
4/67
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
6.1%
10/165
|
3.6%
3/83
|
1.5%
1/67
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
14.5%
24/165
|
6.0%
5/83
|
9.0%
6/67
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
5.5%
9/165
|
4.8%
4/83
|
4.5%
3/67
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
6.1%
10/165
|
1.2%
1/83
|
3.0%
2/67
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
12.1%
20/165
|
4.8%
4/83
|
6.0%
4/67
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
3.6%
6/165
|
3.6%
3/83
|
7.5%
5/67
|
|
Nervous system disorders
Dysgeusia
|
5.5%
9/165
|
1.2%
1/83
|
0.00%
0/67
|
|
Nervous system disorders
Headache
|
20.6%
34/165
|
9.6%
8/83
|
6.0%
4/67
|
|
Psychiatric disorders
Insomnia
|
7.9%
13/165
|
1.2%
1/83
|
3.0%
2/67
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
11.5%
19/165
|
7.2%
6/83
|
6.0%
4/67
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
13.3%
22/165
|
13.3%
11/83
|
11.9%
8/67
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
1.8%
3/165
|
2.4%
2/83
|
7.5%
5/67
|
|
Skin and subcutaneous tissue disorders
Erythema
|
6.1%
10/165
|
1.2%
1/83
|
4.5%
3/67
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
1.8%
3/165
|
7.2%
6/83
|
1.5%
1/67
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
11.5%
19/165
|
2.4%
2/83
|
6.0%
4/67
|
|
Skin and subcutaneous tissue disorders
Rash
|
15.8%
26/165
|
8.4%
7/83
|
6.0%
4/67
|
|
Vascular disorders
Hypertension
|
4.8%
8/165
|
6.0%
5/83
|
1.5%
1/67
|
Additional Information
Study Director
Novartis Pharmaceuticals
Phone: 862-778-8300
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER