Efficacy and Safety of Nilotinib (AMN107) Compared With C... | NCT00471328

ID	Type	Description	Link
2006-002267-11	EudraCT Number

Label	Type	Description	Intervention Names
Nilotinib	Experimental	400mg twice daily in core and extension phases of the study.	Drug: Nilotinib
Control/cross-over to Nilotinib	Active Comparator	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.	Drug: Nilotinib Other: Best Supportive Care (BSC) +/- imatinib or sunitinib

Name	Type	Description	Arm Group Labels	Other Names
Nilotinib	Drug	Nilotinib 400 mg twice daily (bid)	Control/cross-over to Nilotinib Nilotinib

Measure	Description	Time Frame
Progression-free Survival (PFS) From Central Radiology Review Based on Primary Analysis (Data Cut-off: June, 2008)	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.	Up to 16 months
Progression-free Survival (PFS) From Local Investigator's Assessment Based on Treatment Crossover Analysis Set	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.	Up to 34 months

Measure	Description	Time Frame
Overall Survival Based on Primary Analysis (Data Cut-off:June, 2008)	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.	Up to 16 months
Overall Survival During Core and Extension Phases of the Study

Name	Affiliation	Role
Novartis Pharmaceuticals	Novartis Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
UCLA's Jonsson Comprehensive Cancer Center		Los Angeles	California	90095	United States
Washington Hospital Center - Washington Cancer Institute

ID	Title	Description
FG000	Nilotinib	400 mg was taken orally twice daily in core and extension phase of the study
FG001	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.

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Progression-free Survival (PFS) From Central Radiology Review Based on Primary Analysis (Data Cut-off: June, 2008)

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.

The intent to treat (ITT) population was defined as all randomized patients and was used as the primary efficacy population.

Posted

Median

95% Confidence Interval

days

Up to 16 months

ID	Title	Description
OG000	Nilotinib	400 mg was taken orally twice daily in core and extension phase of the study
OG001	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.

Units	Counts
Participants	OG000165 OG00183

Title

Denominators

Categories

Title	Measurements
	OG000109.0(61.0 to 113.0) OG001111.0(60.0 to 116.0)

Secondary

Overall Survival Based on Primary Analysis (Data Cut-off:June, 2008)

The intent to treat (ITT) population was defined as all randomized participants and was used as the primary efficacy population.

Posted

Median

95% Confidence Interval

days

Up to 16 months

ID	Title	Description
OG000	Nilotinib	400 mg was taken orally twice daily in core and extension phase of the study
OG001	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.

Units	Counts
Participants

Secondary

Overall Survival During Core and Extension Phases of the Study

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.

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.

Posted

Median

95% Confidence Interval

days

Up to 50 months (including core, extension and follow up period)

ID	Title	Description
OG000	Nilotinib	400 mg was taken orally twice daily in core and extension phase of the study
OG001	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.

Secondary

Overall Survival for Treatment Crossover Analysis Set

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.

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.

Posted

Median

95% Confidence Interval

days

Up to 34 months

ID	Title	Description
OG000	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 and cross-overed 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.

Units	Counts
Participants	OG000

Primary

Progression-free Survival (PFS) From Local Investigator's Assessment Based on Treatment Crossover Analysis Set

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.

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.

Posted

Median

95% Confidence Interval

days

Up to 34 months

ID	Title	Description
OG000	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 and cross-overed 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.

Units	Counts
Participants

Secondary

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)

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).

The intent to treat (ITT) population was defined as all randomized patients and was used as the primary efficacy population.

Posted

Number

Participants

Up to 16 months

ID	Title	Description
OG000	Nilotinib	400 mg was taken orally twice daily in core and extension phase of the study
OG001	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.

Secondary

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

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).

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.

Posted

Number

Participants

Up to 34 months

ID	Title	Description
OG000	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 and cross-overed 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.

Units	Counts

Secondary

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)

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.

The intent to treat (ITT) population was defined as all randomized patients and was used as the primary efficacy population.

Posted

Number

95% Confidence Interval

Percentage of Participants

Up to 16 months

ID	Title	Description
OG000	Nilotinib	400 mg was taken orally twice daily in core and extension phase of the study
OG001	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.

Secondary

Overall Clinical Benefit (Complete Response [CR]/Partial Response [PR] or Stable Disease [SD]) From Local Investigator's Assessment Based on Treatment Crossover Analysis Set

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.

Posted

Number

95% Confidence Interval

Percentage of Participants

Up to 34 months

ID	Title	Description
OG000	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 and cross-overed 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.

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 14.0	Systematic Assessment	EG0006 affected165 at risk EG0017 affected83 at risk EG0025 affected67 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Angina pectoris	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0002 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Cardiac arrest	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Cyanosis	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Myocardial infarction	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected165 at risk EG0011 affected83 at risk EG0020 affected67 at risk
Sinus bradycardia	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0002 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Spinocerebellar ataxia	Congenital, familial and genetic disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected165 at risk EG0010 affected83 at risk EG0021 affected67 at risk
Hypothyroidism	Endocrine disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected165 at risk EG0011 affected83 at risk EG0020 affected67 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0021 affected67 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG00021 affected165 at risk EG0015 affected83 at risk EG0023 affected67 at risk
Abdominal pain lower	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected165 at risk EG0011 affected83 at risk EG0020 affected67 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0002 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Ascites	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0002 affected165 at risk EG0012 affected83 at risk EG0020 affected67 at risk
Constipation	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0022 affected67 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Duodenal ulcer	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Enteritis	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0003 affected165 at risk EG0012 affected83 at risk EG0022 affected67 at risk
Gastrointestinal motility disorder	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Haematemesis	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Haematochezia	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Ileus	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0002 affected165 at risk EG0010 affected83 at risk EG0021 affected67 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0003 affected165 at risk EG0012 affected83 at risk EG0021 affected67 at risk
Lower gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected165 at risk EG0010 affected83 at risk EG0021 affected67 at risk
Mechanical ileus	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Melaena	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0002 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Nausea	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0003 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Obstruction gastric	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected165 at risk EG0011 affected83 at risk EG0020 affected67 at risk
Oesophageal ulcer	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected165 at risk EG0011 affected83 at risk EG0020 affected67 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Subileus	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0003 affected165 at risk EG0011 affected83 at risk EG0020 affected67 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected165 at risk EG0010 affected83 at risk EG0022 affected67 at risk
Vomiting	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0009 affected165 at risk EG0011 affected83 at risk EG0021 affected67 at risk
Asthenia	General disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected165 at risk EG0011 affected83 at risk EG0021 affected67 at risk
Chest pain	General disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Fatigue	General disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
General physical health deterioration	General disorders	MedDRA 14.0	Systematic Assessment	EG00016 affected165 at risk EG0013 affected83 at risk EG00210 affected67 at risk
Generalised oedema	General disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected165 at risk EG0011 affected83 at risk EG0020 affected67 at risk
Hyperpyrexia	General disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Multi-organ failure	General disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected165 at risk EG0011 affected83 at risk EG0021 affected67 at risk
Oedema peripheral	General disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected165 at risk EG0010 affected83 at risk EG0023 affected67 at risk
Pain	General disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected165 at risk EG0011 affected83 at risk EG0020 affected67 at risk
Performance status decreased	General disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected165 at risk EG0010 affected83 at risk EG0021 affected67 at risk
Pyrexia	General disorders	MedDRA 14.0	Systematic Assessment	EG0005 affected165 at risk EG0012 affected83 at risk EG0021 affected67 at risk
Cholestasis	Hepatobiliary disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Hepatic failure	Hepatobiliary disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected165 at risk EG0011 affected83 at risk EG0020 affected67 at risk
Hepatomegaly	Hepatobiliary disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Hepatorenal failure	Hepatobiliary disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected165 at risk EG0010 affected83 at risk EG0021 affected67 at risk
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Portal vein thrombosis	Hepatobiliary disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected165 at risk EG0010 affected83 at risk EG0021 affected67 at risk
Abdominal infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0000 affected165 at risk EG0010 affected83 at risk EG0021 affected67 at risk
Alpha haemolytic streptococcal infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Bacteraemia	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0011 affected83 at risk EG0020 affected67 at risk
Bacterial sepsis	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Empyema	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Escherichia infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Fungaemia	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0000 affected165 at risk EG0010 affected83 at risk EG0021 affected67 at risk
Klebsiella sepsis	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0000 affected165 at risk EG0011 affected83 at risk EG0020 affected67 at risk
Perihepatic abscess	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Pneumonia	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0002 affected165 at risk EG0011 affected83 at risk EG0022 affected67 at risk
Pneumonia haemophilus	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Pyelonephritis acute	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0000 affected165 at risk EG0010 affected83 at risk EG0021 affected67 at risk
Sepsis	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Septic shock	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0011 affected83 at risk EG0020 affected67 at risk
Staphylococcal infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Urinary tract infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0000 affected165 at risk EG0010 affected83 at risk EG0021 affected67 at risk
Overdose	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0000 affected165 at risk EG0011 affected83 at risk EG0020 affected67 at risk
Blood creatinine increased	Investigations	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Haemoglobin decreased	Investigations	MedDRA 14.0	Systematic Assessment	EG0000 affected165 at risk EG0010 affected83 at risk EG0021 affected67 at risk
Weight decreased	Investigations	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG0002 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG0002 affected165 at risk EG0011 affected83 at risk EG0021 affected67 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0021 affected67 at risk
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected165 at risk EG0010 affected83 at risk EG0021 affected67 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Hypovolaemia	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Malnutrition	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected165 at risk EG0011 affected83 at risk EG0020 affected67 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Systematic Assessment	EG0003 affected165 at risk EG0011 affected83 at risk EG0021 affected67 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Brain neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.0	Systematic Assessment	EG0000 affected165 at risk EG0010 affected83 at risk EG0021 affected67 at risk
Infected neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.0	Systematic Assessment	EG0002 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Metastases to liver	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Rectal cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Tumour compression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.0	Systematic Assessment	EG0000 affected165 at risk EG0010 affected83 at risk EG0021 affected67 at risk
Tumour haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0021 affected67 at risk
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0011 affected83 at risk EG0020 affected67 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Coma	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected165 at risk EG0010 affected83 at risk EG0021 affected67 at risk
Convulsion	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Depressed level of consciousness	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Headache	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected165 at risk EG0011 affected83 at risk EG0020 affected67 at risk
Hepatic encephalopathy	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Metabolic encephalopathy	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Nystagmus	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected165 at risk EG0010 affected83 at risk EG0021 affected67 at risk
Haematuria	Renal and urinary disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Hydronephrosis	Renal and urinary disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected165 at risk EG0010 affected83 at risk EG0021 affected67 at risk
Renal failure acute	Renal and urinary disorders	MedDRA 14.0	Systematic Assessment	EG0002 affected165 at risk EG0010 affected83 at risk EG0022 affected67 at risk
Urinary retention	Renal and urinary disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Pelvic pain	Reproductive system and breast disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected165 at risk EG0011 affected83 at risk EG0020 affected67 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0004 affected165 at risk EG0011 affected83 at risk EG0024 affected67 at risk
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Lung disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected165 at risk EG0011 affected83 at risk EG0020 affected67 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0012 affected83 at risk EG0021 affected67 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0003 affected165 at risk EG0012 affected83 at risk EG0022 affected67 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected165 at risk EG0011 affected83 at risk EG0020 affected67 at risk
Hypotension	Vascular disorders	MedDRA 14.0	Systematic Assessment	EG0002 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Inferior vena caval occlusion	Vascular disorders	MedDRA 14.0	Systematic Assessment	EG0000 affected165 at risk EG0010 affected83 at risk EG0021 affected67 at risk
Intra-abdominal haemorrhage	Vascular disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk
Venous thrombosis limb	Vascular disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0010 affected83 at risk EG0020 affected67 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 14.0	Systematic Assessment	EG00039 affected165 at risk EG00117 affected83 at risk EG00212 affected67 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 14.0	Systematic Assessment	EG0001 affected165 at risk EG0017 affected83 at risk EG0020 affected67 at risk
Eyelid oedema	Eye disorders	MedDRA 14.0	Systematic Assessment	EG0003 affected165 at risk EG0017 affected83 at risk EG0020 affected67 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG00017 affected165 at risk EG0016 affected83 at risk EG0025 affected67 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG00061 affected165 at risk EG00119 affected83 at risk EG00213 affected67 at risk
Abdominal pain lower	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0003 affected165 at risk EG0013 affected83 at risk EG0024 affected67 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG00021 affected165 at risk EG0016 affected83 at risk EG0028 affected67 at risk
Ascites	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0003 affected165 at risk EG0015 affected83 at risk EG0023 affected67 at risk
Constipation	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG00041 affected165 at risk EG0019 affected83 at risk EG00210 affected67 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG00028 affected165 at risk EG00120 affected83 at risk EG0025 affected67 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG00013 affected165 at risk EG0016 affected83 at risk EG0021 affected67 at risk
Nausea	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG00051 affected165 at risk EG00133 affected83 at risk EG00213 affected67 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG00013 affected165 at risk EG0014 affected83 at risk EG0021 affected67 at risk
Vomiting	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG00033 affected165 at risk EG00125 affected83 at risk EG00214 affected67 at risk
Asthenia	General disorders	MedDRA 14.0	Systematic Assessment	EG00046 affected165 at risk EG0016 affected83 at risk EG0029 affected67 at risk
Fatigue	General disorders	MedDRA 14.0	Systematic Assessment	EG00046 affected165 at risk EG00115 affected83 at risk EG00212 affected67 at risk
Oedema peripheral	General disorders	MedDRA 14.0	Systematic Assessment	EG00030 affected165 at risk EG00126 affected83 at risk EG00213 affected67 at risk
Pyrexia	General disorders	MedDRA 14.0	Systematic Assessment	EG00031 affected165 at risk EG0017 affected83 at risk EG0028 affected67 at risk
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA 14.0	Systematic Assessment	EG00014 affected165 at risk EG0011 affected83 at risk EG0024 affected67 at risk
Alanine aminotransferase increased	Investigations	MedDRA 14.0	Systematic Assessment	EG00014 affected165 at risk EG0011 affected83 at risk EG0020 affected67 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 14.0	Systematic Assessment	EG00012 affected165 at risk EG0016 affected83 at risk EG0020 affected67 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 14.0	Systematic Assessment	EG00015 affected165 at risk EG0014 affected83 at risk EG0021 affected67 at risk
Lipase increased	Investigations	MedDRA 14.0	Systematic Assessment	EG00011 affected165 at risk EG0010 affected83 at risk EG0021 affected67 at risk
Weight decreased	Investigations	MedDRA 14.0	Systematic Assessment	EG00034 affected165 at risk EG0017 affected83 at risk EG00220 affected67 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG00047 affected165 at risk EG00118 affected83 at risk EG00216 affected67 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG00010 affected165 at risk EG0012 affected83 at risk EG0022 affected67 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG0008 affected165 at risk EG0013 affected83 at risk EG0024 affected67 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG0007 affected165 at risk EG0015 affected83 at risk EG0022 affected67 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG0009 affected165 at risk EG0013 affected83 at risk EG0024 affected67 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Systematic Assessment	EG00010 affected165 at risk EG0013 affected83 at risk EG0021 affected67 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Systematic Assessment	EG00024 affected165 at risk EG0015 affected83 at risk EG0026 affected67 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Systematic Assessment	EG0009 affected165 at risk EG0014 affected83 at risk EG0023 affected67 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Systematic Assessment	EG00010 affected165 at risk EG0011 affected83 at risk EG0022 affected67 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Systematic Assessment	EG00020 affected165 at risk EG0014 affected83 at risk EG0024 affected67 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Systematic Assessment	EG0006 affected165 at risk EG0013 affected83 at risk EG0025 affected67 at risk
Dysgeusia	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0009 affected165 at risk EG0011 affected83 at risk EG0020 affected67 at risk
Headache	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG00034 affected165 at risk EG0018 affected83 at risk EG0024 affected67 at risk
Insomnia	Psychiatric disorders	MedDRA 14.0	Systematic Assessment	EG00013 affected165 at risk EG0011 affected83 at risk EG0022 affected67 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG00019 affected165 at risk EG0016 affected83 at risk EG0024 affected67 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG00022 affected165 at risk EG00111 affected83 at risk EG0028 affected67 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0003 affected165 at risk EG0012 affected83 at risk EG0025 affected67 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 14.0	Systematic Assessment	EG00010 affected165 at risk EG0011 affected83 at risk EG0023 affected67 at risk
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA 14.0	Systematic Assessment	EG0003 affected165 at risk EG0016 affected83 at risk EG0021 affected67 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 14.0	Systematic Assessment	EG00019 affected165 at risk EG0012 affected83 at risk EG0024 affected67 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 14.0	Systematic Assessment	EG00026 affected165 at risk EG0017 affected83 at risk EG0024 affected67 at risk
Hypertension	Vascular disorders	MedDRA 14.0	Systematic Assessment	EG0008 affected165 at risk EG0015 affected83 at risk EG0021 affected67 at risk

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Nilotinib(Core +Extension)	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.	81	165	159	165
EG001	Control(Core + Extension)	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.	27	83	73	83
EG002	Crossover Nilotinib Therapy	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.	32	67	58	67

ID	Term
D009372	Neoplasms, Connective Tissue
D018204	Neoplasms, Connective and Soft Tissue
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D005770	Gastrointestinal Neoplasms
D004067	Digestive System Neoplasms
D004066	Digestive System Diseases
D005767	Gastrointestinal Diseases

ID	Term
C498826	nilotinib
D000068877	Imatinib Mesylate
D000077210	Sunitinib

ID	Term
D001549	Benzamides
D000577	Amides
D009930	Organic Chemicals
D001565	Benzoates
D000146	Acids, Carbocyclic
D002264	Carboxylic Acids
D001555	Benzene Derivatives
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D010879	Piperazines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D011743	Pyrimidines
D011758	Pyrroles
D001393	Azoles
D007211	Indoles
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring

ID	Title	Description
BG000	Nilotinib	400 mg was taken orally twice daily in core and extension phase of the study
BG001	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.
BG002	Total	Total of all reporting groups