A Study of the Efficacy and Safety of Imatinib Mesylate in Patients With Unresectable or Metastatic Gastrointestinal Stromal Tumors Expressing C-kit Gene

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00237185
• Collaborator: (none)
• Enrollment: 148
• Locations: 5
• Arms: 2
• Duration (Months): 156
• Patients Per Site: 29.6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

In the core study, participants with unresectable or metastatic gastrointestinal stromal tumors expressing c-kit were treated with either 400 mg or 600 mg imatinib mesylate for 3 years. The 10 year extension study allowed participants, who successfully completed the core study, to continue study treatment with imatinib mesylate provided they still benefited from treatment and did not demonstrate safety concerns as per the investigator's opinion.

Condition or Disease	Intervention/Treatment	Phase
Unresectable or Metastatic Malignant Gastrointestinal Stromal Tumor (GIST)	Drug: Imatinib mesylate	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 148 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open, Randomized, Phase II Study of Glivec in Patients With Unresectable or Metastatic Gastrointestinal Stromal Tumors Expressing C-kit Plus 10 Year Extension Study
• Study Start Date: Jun 1, 2000
• Actual Primary Completion Date: Jun 1, 2013
• Actual Study Completion Date: Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: imatinib mesylate 400 mg 400 mg once daily	Drug: Imatinib mesylate; Participants were randomized 1:1 to receive imatinib mesylate 400 mg/day or 600 mg/day. Upon unsatisfactory treatment effect on the starting dose of 400 mg/day or 600 mg/day imatinib mesylate, in the opinion of the treating physician, a dose increase up to 600 mg/day or 800 mg/day, was allowed provided that the participant continued to benefit from the treatment and in the absence of safety concerns.; Other Names: Glivec, Gleevec
Experimental: imatinib mesylate 600 mg 600 mg once daily	Drug: Imatinib mesylate; Participants were randomized 1:1 to receive imatinib mesylate 400 mg/day or 600 mg/day. Upon unsatisfactory treatment effect on the starting dose of 400 mg/day or 600 mg/day imatinib mesylate, in the opinion of the treating physician, a dose increase up to 600 mg/day or 800 mg/day, was allowed provided that the participant continued to benefit from the treatment and in the absence of safety concerns.; Other Names: Glivec, Gleevec

Outcome Measures

Primary Outcome Measures

1. Best Tumor Response (Core) [Month 36]

   Best tumor response was based on the Southwestern Oncology Group (SWOG) criteria. Objective tumor response assessments were categorized according to the following criteria: complete response (CR), partial response (PR), no change or stable disease (SD), progression of disease (PD), unknown where the progression has not been documented and one or more measurable or evaluable sites have not been assessed (UNK), status after resection for progression (RP), status after resection for safety (RS), status after preventive resection (RPR), progressive after first resection (PDR) and not evaluable. Any tumor assessment after surgical resection for preventative reasons was treated like tumor assessments of UNK for calculation of best response. Tumor assessments with current objective status = RP, RS or PDR were treated like assessments with objective tumor status = PD n the calculation of best response.

2. Best Tumor Response (Core + Extension) [Month 156]

   Best tumor response was based on the Southwestern Oncology Group (SWOG) criteria. Objective tumor response assessments were categorized according to the following criteria: complete response (CR), partial response (PR), no change or stable disease (SD), progression of disease (PD), unknown where the progression has not been documented and one or more measurable or evaluable sites have not been assessed (UNK), status after resection for progression (RP), status after resection for safety (RS), status after preventive resection (RPR), progressive after first resection (PDR) and not evaluable. Any tumor assessment after surgical resection for preventative reasons was treated like tumor assessments of UNK for calculation of best response. Tumor assessments with current objective status = RP, RS or PDR were treated like assessments with objective tumor status = PD n the calculation of best response.

Secondary Outcome Measures

1. Overall Survival (Core) [Date of first imatinib dose to the date of death during the core period, up to 36 months.]

   Overall survival was analyzed as time to event for all participants. Participants who did not die were censored at the last date known alive, which is the last date of any study medication, laboratory sample, tumor assessment, adverse event end date or date of last contact.

2. Overall Survival (Core + Extension) [Date of first imatinib dose to the date of death during the core and extension periods, up to 156 months.]

   Overall survival was analyzed as time to event for all participants. Participants who did not die were censored at the last date known alive, which is the last date of any study medication, laboratory sample, tumor assessment, adverse event end date or date of last contact.

3. Duration of Response (Core) [Date of confirmed best PR or CR to date of confirmed disease progression during the core period, up to 36 months.]

   Duration of response was analyzed as time to event for all participants whose best response was at least a PR. The onset of response was the first tumor assessment that was subsequently confirmed to constitute at least a partial best response. The end of response was the first tumor assessment noting PD.

4. Duration of Response (Core + Extension) [Date of confirmed best PR or CR to date of confirmed disease progression during the core and extension periods, up to 156 months]

   Duration of response was analyzed as time to event for all participants whose best response was at least a PR. The onset of response was the first tumor assessment that was subsequently confirmed to constitute at least a partial best response. The end of response was the first tumor assessment noting PD.

5. Progression Free Survival (PFS) (Core + Extension) [Date of first imatinib dose to earliest date of progression, resection due to safety/progression, death due to any cause or discontinuation due to unsatisfactory therapeutic effect during the core and extension periods, up to 156 months.]

   Progression free survival was analyzed as a time to event for each participant. If a participant had no event, then the PFS was censored at the last tumor assessment.

6. Time to Treatment Failure (Core) [Date of first imatinib dose to date of earliest occurrence of progression, death due to any cause, or discontinuation from the trial for any reason other than the condition no longer required therapy during the core period, up to 36 months.]

   Time to treatment failure was analyzed as time to event for all participants. Participants who had neither progressed, died nor discontinued from the trial for any reason other than the condition no longer required therapy were censored for analysis ate the time of their last tumor assessment.

7. Time to Treatment Failure (Core + Extension) [Date of first imatinib dose to date of earliest occurrence of progression, death due to any cause, or discontinuation from the trial for any reason other than the condition no longer required therapy during the core and extension periods, up to 156 month.]

   Time to treatment failure was analyzed as time to event for all participants. Participants who had neither progressed, died nor discontinued from the trial for any reason other than the condition no longer required therapy were censored for analysis at the time of their last tumor assessment.

8. Time to Onset of Response (Core) [Date of first imatinib dose to the date of the first tumor assessment that was later confirmed to be at least a partial response during the core period, up to 36 months.]

   Time to response was analyzed as time to event for all participants. Participants who did not meet the definition of confirmed PR/CR were censored at the time of their last progression-free tumor assessment.

9. Time to Onset of Response (Core + Extension) [Date of first imatinib dose to the date of the first tumor assessment that was later confirmed to be at least a partial response during the core and extension periods, up to 156 months.]

   Time to response was analyzed as time to event for all participants. Participants who did not meet the definition of confirmed PR/CR were censored at the time of their last progression-free tumor assessment.

10. Time to Progression (Core + Extension) [Date of first imatinib dose to date of progression or death due to disease indication or discontinuation due to unsatisfactory therapeutic effect during the core and extension periods, up to 156 months.]

    Time to progression was analyzed as time to event for all participants. Participants who had neither progressed, died nor discontinued from the trial for any reason other than the condition no longer required therapy were censored for analysis at the time of their last tumor assessment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Men and non-pregnant women ≥18 years of age with the histopathologically documented diagnosis of malignant GIST that was unresectable and/or metastatic. Confirmation of KIT (CD117) expression via immunohistochemical analysis of tumor sample was also required

• At least one measurable lesion, as defined by Southwestern Oncology Group (SWOG) Solid Tumor Response Criteria, which had not been previously embolized or irradiated

• Performance status ≤3 as defined by the Eastern Cooperative Oncology Group (ECOG) criteria, as well as a life expectancy ≥6 months and adequate end organ function defined as follows: Total bilirubin <1.5 times upper limit of normal (ULN), aspartate aminotransferase (SGOT) and alanine aminotransferase (SGPT) <2.5 x ULN (or <5 x ULN if hepatic metastases were present), creatinine <1.5 x ULN, absolute neutrophil count (ANC) >1.5 x 10^{9/L, platelet count >100 x 10}9/L

Exclusion Criteria:

• Patients with fewer than five years of disease-free survival from any other (non-GIST) malignancy except if the other malignancy was not currently clinically significant and did not require active intervention or if the other malignancy was a basal cell skin cancer or a cervical carcinoma in situ

• Patients with known brain metastases

• Evidence of any of the following disorders: Grade III/IV cardiac failure as defined by the New York Heart Association Criteria, severe concomitant disease, acute or known chronic liver disease (i.e. chronic active hepatitis, cirrhosis) or HIV infection

• Chemotherapy or other investigational therapy within four weeks prior to study entry (six weeks for nitrosourea or mitomycin-C) and/or radiotherapy to ≥25% of the bone marrow

• Inability to cooperate

• Major surgery within two weeks or exposure to other investigational agents within 28 days of entry into the study

Other protocol-defined inclusion / exclusion criteria may have applied.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dana Farber Cancer Institute Dept of Sarcoma Oncology	Boston	Massachusetts	United States	02115
2	Oregon Health Sciences University Dept. of Oregon Health Sci.	Portland	Oregon	United States	97201
3	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
4	Novartis Investigative Site	Geelong	Victoria	Australia	3220
5	Novartis Investigative Site	Helsinki		Finland	FIN-00029

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
• Study Chair: Novartis, Novartis

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00237185
• Other Study ID Numbers: CSTI571B2222; CSTI571B2222/E1
• First Posted: Oct 12, 2005
• Last Update Posted: Aug 19, 2014
• Last Verified: Aug 1, 2014

• Keywords provided by Novartis Pharmaceuticals: GIST; c-kit; imatinib mesylate
• Additional relevant MeSH terms: Gastrointestinal Stromal Tumors; Imatinib Mesylate

Study Results

Participant Flow

Arm/Group Title	Imatinib Mesylate 400 mg	Imatinib Mesylate 600 mg
Arm/Group Description	imatinib mesylate 400 mg once daily	imatinib mesylate 600 mg once daily
Period Title: Core
STARTED	74	74
Treated Participants	73	74
COMPLETED	30	37
NOT COMPLETED	44	37
Period Title: Core
STARTED	24	32
COMPLETED	8	13
NOT COMPLETED	16	19

Baseline Characteristics

Arm/Group Title	Imatinib Mesylate 400 mg	Imatinib Mesylate 600 mg	Total
Arm/Group Description	400 mg Imatinib mesylate	600 mg Imatinib mesylate	Total of all reporting groups
Overall Participants	73	74	147
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	56.6 (12.9)	52.2 (11.12)	54.4 (12.2)
Sex: Female, Male (Count of Participants)
Female	29 39.7%	35 47.3%	64 43.5%
Male	44 60.3%	39 52.7%	83 56.5%

Outcome Measures

1. Primary Outcome

Title	Best Tumor Response (Core)
Description	Best tumor response was based on the Southwestern Oncology Group (SWOG) criteria. Objective tumor response assessments were categorized according to the following criteria: complete response (CR), partial response (PR), no change or stable disease (SD), progression of disease (PD), unknown where the progression has not been documented and one or more measurable or evaluable sites have not been assessed (UNK), status after resection for progression (RP), status after resection for safety (RS), status after preventive resection (RPR), progressive after first resection (PDR) and not evaluable. Any tumor assessment after surgical resection for preventative reasons was treated like tumor assessments of UNK for calculation of best response. Tumor assessments with current objective status = RP, RS or PDR were treated like assessments with objective tumor status = PD n the calculation of best response.
Time Frame	Month 36

Outcome Measure Data

Analysis Population Description

Treatment population: The treatment population included all randomized participants who received at least one dose of study medication.

Arm/Group Title	Imatinib Mesylate 400 mg	Imatinib Mesylate 600 mg
Arm/Group Description	400 mg Imatinib mesylate	600 mg Imatinib mesylate
Measure Participants	73	74
Complete response	0 0%	1 1.4%
Partial response	49 67.1%	49 66.2%
Stable disease	10 13.7%	13 17.6%
Progressive disease	12 16.4%	6 8.1%
Not evaluable	2 2.7%	3 4.1%
Unknown	0 0%	2 2.7%

2. Primary Outcome

Title	Best Tumor Response (Core + Extension)
Description	Best tumor response was based on the Southwestern Oncology Group (SWOG) criteria. Objective tumor response assessments were categorized according to the following criteria: complete response (CR), partial response (PR), no change or stable disease (SD), progression of disease (PD), unknown where the progression has not been documented and one or more measurable or evaluable sites have not been assessed (UNK), status after resection for progression (RP), status after resection for safety (RS), status after preventive resection (RPR), progressive after first resection (PDR) and not evaluable. Any tumor assessment after surgical resection for preventative reasons was treated like tumor assessments of UNK for calculation of best response. Tumor assessments with current objective status = RP, RS or PDR were treated like assessments with objective tumor status = PD n the calculation of best response.
Time Frame	Month 156

Outcome Measure Data

Analysis Population Description

Treatment population: the treatment population included all participants who had at least one dose of study medication.

Arm/Group Title	Imatinib Mesylate 400 mg	Imatinib Mesylate 600 mg
Arm/Group Description	400 mg Imatinib mesylate	600 mg Imatinib mesylate
Measure Participants	73	74
Complete response	1 1.4%	2 2.7%
Partial response	49 67.1%	48 64.9%
Stable disease	10 13.7%	13 17.6%
Progressive disease	11 15.1%	6 8.1%
Not evaluable	2 2.7%	3 4.1%
Unknown	0 0%	2 2.7%

3. Secondary Outcome

Title	Overall Survival (Core)
Description	Overall survival was analyzed as time to event for all participants. Participants who did not die were censored at the last date known alive, which is the last date of any study medication, laboratory sample, tumor assessment, adverse event end date or date of last contact.
Time Frame	Date of first imatinib dose to the date of death during the core period, up to 36 months.

Outcome Measure Data

Analysis Population Description

Treatment population: the treatment population included all participants who had at least one dose of study medication.

Arm/Group Title	Imatinib Mesylate 400 mg	Imatinib Mesylate 600 mg
Arm/Group Description	400 mg Imatinib mesylate	600 mg Imatinib mesylate
Measure Participants	73	74
Median (95% Confidence Interval) [months]	NA	NA

4. Secondary Outcome

Title	Overall Survival (Core + Extension)
Description	Overall survival was analyzed as time to event for all participants. Participants who did not die were censored at the last date known alive, which is the last date of any study medication, laboratory sample, tumor assessment, adverse event end date or date of last contact.
Time Frame	Date of first imatinib dose to the date of death during the core and extension periods, up to 156 months.

Outcome Measure Data

Analysis Population Description

Treatment population: the treatment population included all participants who had at least one dose of study medication.

Arm/Group Title	Imatinib Mesylate 400 mg	Imatinib Mesylate 600 mg
Arm/Group Description	400 mg Imatinib mesylate	600 mg Imatinib mesylate
Measure Participants	73	74
Median (95% Confidence Interval) [months]	55.9	57.1

5. Secondary Outcome

Title	Duration of Response (Core)
Description	Duration of response was analyzed as time to event for all participants whose best response was at least a PR. The onset of response was the first tumor assessment that was subsequently confirmed to constitute at least a partial best response. The end of response was the first tumor assessment noting PD.
Time Frame	Date of confirmed best PR or CR to date of confirmed disease progression during the core period, up to 36 months.

Outcome Measure Data

Analysis Population Description

Treatment population: the treatment population included all participants who had at least one dose of study medication and whose best response was at least a PR.

Arm/Group Title	Imatinib Mesylate 400 mg	Imatinib Mesylate 600 mg
Arm/Group Description	400 mg Imatinib mesylate	600 mg Imatinib mesylate
Measure Participants	49	50
Median (95% Confidence Interval) [weeks]	113	123

6. Secondary Outcome

Title	Duration of Response (Core + Extension)
Description	Duration of response was analyzed as time to event for all participants whose best response was at least a PR. The onset of response was the first tumor assessment that was subsequently confirmed to constitute at least a partial best response. The end of response was the first tumor assessment noting PD.
Time Frame	Date of confirmed best PR or CR to date of confirmed disease progression during the core and extension periods, up to 156 months

Outcome Measure Data

Analysis Population Description

Treatment population: the treatment population included all participants who had at least one dose of study medication and whose best response was at least a PR.

Arm/Group Title	Imatinib Mesylate 400 mg	Imatinib Mesylate 600 mg
Arm/Group Description	400 mg Imatinib mesylate	600 mg Imatinib mesylate
Measure Participants	49	50
Median (95% Confidence Interval) [months]	27	30

7. Secondary Outcome

Title	Progression Free Survival (PFS) (Core + Extension)
Description	Progression free survival was analyzed as a time to event for each participant. If a participant had no event, then the PFS was censored at the last tumor assessment.
Time Frame	Date of first imatinib dose to earliest date of progression, resection due to safety/progression, death due to any cause or discontinuation due to unsatisfactory therapeutic effect during the core and extension periods, up to 156 months.

Outcome Measure Data

Analysis Population Description

Treatment population: the treatment population included all participants who had at least one dose of study medication.

Arm/Group Title	Imatinib Mesylate 400 mg	Imatinib Mesylate 600 mg
Arm/Group Description	400 mg Imatinib mesylate	600 mg Imatinib mesylate
Measure Participants	73	74
Median (95% Confidence Interval) [months]	19.3	25.2

8. Secondary Outcome

Title	Time to Treatment Failure (Core)
Description	Time to treatment failure was analyzed as time to event for all participants. Participants who had neither progressed, died nor discontinued from the trial for any reason other than the condition no longer required therapy were censored for analysis ate the time of their last tumor assessment.
Time Frame	Date of first imatinib dose to date of earliest occurrence of progression, death due to any cause, or discontinuation from the trial for any reason other than the condition no longer required therapy during the core period, up to 36 months.

Outcome Measure Data

Analysis Population Description

Treatment population: the treatment population included all participants who received at least one dose of study medication.

Arm/Group Title	Imatinib Mesylate 400 mg	Imatinib Mesylate 600 mg
Arm/Group Description	400 mg Imatinib mesylate	600 mg Imatinib mesylate
Measure Participants	73	74
Median (95% Confidence Interval) [weeks]	84	84

9. Secondary Outcome

Title	Time to Treatment Failure (Core + Extension)
Description	Time to treatment failure was analyzed as time to event for all participants. Participants who had neither progressed, died nor discontinued from the trial for any reason other than the condition no longer required therapy were censored for analysis at the time of their last tumor assessment.
Time Frame	Date of first imatinib dose to date of earliest occurrence of progression, death due to any cause, or discontinuation from the trial for any reason other than the condition no longer required therapy during the core and extension periods, up to 156 month.

Outcome Measure Data

Analysis Population Description

Treatment population: the treatment population included all participants who received at least one dose of study medication.

Arm/Group Title	Imatinib Mesylate 400 mg	Imatinib Mesylate 600 mg
Arm/Group Description	400 mg Imatinib mesylate	600 mg Imatinib mesylate
Measure Participants	73	74
Median (95% Confidence Interval) [months]	19	19

10. Secondary Outcome

Title	Time to Onset of Response (Core)
Description	Time to response was analyzed as time to event for all participants. Participants who did not meet the definition of confirmed PR/CR were censored at the time of their last progression-free tumor assessment.
Time Frame	Date of first imatinib dose to the date of the first tumor assessment that was later confirmed to be at least a partial response during the core period, up to 36 months.

Outcome Measure Data

Analysis Population Description

Treatment population: the treatment population included all participants who received at least one dose of study medication.

Arm/Group Title	Imatinib Mesylate 400 mg	Imatinib Mesylate 600 mg
Arm/Group Description	400 mg Imatinib mesylate	600 mg Imatinib mesylate
Measure Participants	73	74
Median (95% Confidence Interval) [weeks]	13	12

11. Secondary Outcome

Title	Time to Onset of Response (Core + Extension)
Description	Time to response was analyzed as time to event for all participants. Participants who did not meet the definition of confirmed PR/CR were censored at the time of their last progression-free tumor assessment.
Time Frame	Date of first imatinib dose to the date of the first tumor assessment that was later confirmed to be at least a partial response during the core and extension periods, up to 156 months.

Outcome Measure Data

Analysis Population Description

Treatment population: the treatment population included all participants who received at least one dose of study medication.

Arm/Group Title	Imatinib Mesylate 400 mg	Imatinib Mesylate 600 mg
Arm/Group Description	400 mg Imatinib mesylate	600 mg Imatinib mesylate
Measure Participants	73	74
Median (95% Confidence Interval) [months]	3	3

12. Secondary Outcome

Title	Time to Progression (Core + Extension)
Description	Time to progression was analyzed as time to event for all participants. Participants who had neither progressed, died nor discontinued from the trial for any reason other than the condition no longer required therapy were censored for analysis at the time of their last tumor assessment.
Time Frame	Date of first imatinib dose to date of progression or death due to disease indication or discontinuation due to unsatisfactory therapeutic effect during the core and extension periods, up to 156 months.

Outcome Measure Data

Analysis Population Description

Treatment population: the treatment population included all participants who received at least one dose of study medication.

Arm/Group Title	Imatinib Mesylate 400 mg	Imatinib Mesylate 600 mg
Arm/Group Description	400 mg Imatinib mesylate	600 mg Imatinib mesylate
Measure Participants	73	74
Median (95% Confidence Interval) [months]	19.8	25.5

Adverse Events

Arm/Group Title	Imatinib Mesylate 400 mg		Imatinib Mesylate 600 mg
Arm/Group Description	400 mg		600 mg
All Cause Mortality
	Imatinib Mesylate 400 mg		Imatinib Mesylate 600 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Imatinib Mesylate 400 mg		Imatinib Mesylate 600 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	46/73 (63%)		40/74 (54.1%)
Blood and lymphatic system disorders
Anaemia NOS	2/73 (2.7%)		4/74 (5.4%)
Disseminated intravascular coagulation	0/73 (0%)		1/74 (1.4%)
Neutropenia	2/73 (2.7%)		0/74 (0%)
Cardiac disorders
Bradyarrhythmia	1/73 (1.4%)		0/74 (0%)
Cardiac arrest	1/73 (1.4%)		1/74 (1.4%)
Myocardial infarction	0/73 (0%)		1/74 (1.4%)
Ventricular fibrillation	0/73 (0%)		1/74 (1.4%)
Gastrointestinal disorders
Abdominal pain NOS	5/73 (6.8%)		3/74 (4.1%)
Abdominal pain upper	0/73 (0%)		1/74 (1.4%)
Ascites	0/73 (0%)		1/74 (1.4%)
Colovesical fistula	1/73 (1.4%)		0/74 (0%)
Constipation	1/73 (1.4%)		0/74 (0%)
Diarrhoea NOS	0/73 (0%)		2/74 (2.7%)
Diverticular perforation NOS	1/73 (1.4%)		0/74 (0%)
Dysphagia	1/73 (1.4%)		0/74 (0%)
Gastrointestinal haemorrhage NOS	3/73 (4.1%)		2/74 (2.7%)
Gastrooesophageal reflux disease	1/73 (1.4%)		0/74 (0%)
Ileus	1/73 (1.4%)		1/74 (1.4%)
Inflammatory bowel disease NOS	1/73 (1.4%)		0/74 (0%)
Intestinal obstruction NOS	2/73 (2.7%)		2/74 (2.7%)
Melaena	0/73 (0%)		1/74 (1.4%)
Nausea	2/73 (2.7%)		3/74 (4.1%)
Pancreatitis NOS	0/73 (0%)		1/74 (1.4%)
Small intestinal obstruction NOS	3/73 (4.1%)		2/74 (2.7%)
Vomiting NOS	1/73 (1.4%)		2/74 (2.7%)
General disorders
Anasarca	1/73 (1.4%)		0/74 (0%)
Asthenia	0/73 (0%)		1/74 (1.4%)
Chest pain	1/73 (1.4%)		1/74 (1.4%)
Disease progression NOS	1/73 (1.4%)		1/74 (1.4%)
Inflammation NOS	0/73 (0%)		1/74 (1.4%)
Oedema peripheral	1/73 (1.4%)		0/74 (0%)
Pain NOS	0/73 (0%)		1/74 (1.4%)
Pain exacerbated	1/73 (1.4%)		0/74 (0%)
Pyrexia	3/73 (4.1%)		2/74 (2.7%)
Rigors	1/73 (1.4%)		0/74 (0%)
Hepatobiliary disorders
Cholangitis NOS	0/73 (0%)		1/74 (1.4%)
Cholecystitis NOS	0/73 (0%)		1/74 (1.4%)
Cholelithiasis	0/73 (0%)		1/74 (1.4%)
Hyperbilirubinaemia	0/73 (0%)		1/74 (1.4%)
Infections and infestations
Abdominal abscess NOS	1/73 (1.4%)		0/74 (0%)
Abscess intestinal	1/73 (1.4%)		0/74 (0%)
Bacteraemia	1/73 (1.4%)		1/74 (1.4%)
Bronchopneumonia NOS	1/73 (1.4%)		0/74 (0%)
Catheter related infection	0/73 (0%)		1/74 (1.4%)
Cellulitis	1/73 (1.4%)		0/74 (0%)
Escherichia sepsis	0/73 (0%)		1/74 (1.4%)
Klebsiella infection NOS	1/73 (1.4%)		0/74 (0%)
Lung infection NOS	1/73 (1.4%)		0/74 (0%)
Orchitis NOS	1/73 (1.4%)		0/74 (0%)
Pneumonia NOS	1/73 (1.4%)		1/74 (1.4%)
Pneumonia primary atypical	1/73 (1.4%)		0/74 (0%)
Pseudomonas infection NOS	0/73 (0%)		1/74 (1.4%)
Sepsis NOS	2/73 (2.7%)		0/74 (0%)
Staphylococcal infection	1/73 (1.4%)		0/74 (0%)
Tooth abscess	1/73 (1.4%)		0/74 (0%)
Urinary tract infection NOS	0/73 (0%)		1/74 (1.4%)
Urosepsis	0/73 (0%)		1/74 (1.4%)
Wound infection	1/73 (1.4%)		0/74 (0%)
Injury, poisoning and procedural complications
Fall	1/73 (1.4%)		0/74 (0%)
Femur fracture	1/73 (1.4%)		0/74 (0%)
Intestinal anastomotic leak	1/73 (1.4%)		0/74 (0%)
Lumbar vertebral fracture	1/73 (1.4%)		0/74 (0%)
Post procedural haemorrhage	0/73 (0%)		1/74 (1.4%)
Postoperative haematoma	0/73 (0%)		1/74 (1.4%)
Thoracic vertebral fracture	1/73 (1.4%)		0/74 (0%)
Wound NOS	1/73 (1.4%)		0/74 (0%)
Wound complication	1/73 (1.4%)		0/74 (0%)
Wrist fracture	1/73 (1.4%)		0/74 (0%)
Investigations
Alanine aminotransferase increased	0/73 (0%)		1/74 (1.4%)
Aspartate aminotransferase increased	0/73 (0%)		1/74 (1.4%)
Blood bilirubin increased	1/73 (1.4%)		0/74 (0%)
Blood creatine phosphokinase increased	1/73 (1.4%)		0/74 (0%)
Blood creatinine increased	0/73 (0%)		1/74 (1.4%)
Blood lactate dehydrogenase increased	0/73 (0%)		1/74 (1.4%)
Liver function test abnormal	2/73 (2.7%)		0/74 (0%)
Metabolism and nutrition disorders
Dehydration	3/73 (4.1%)		1/74 (1.4%)
Hypercalcaemia	1/73 (1.4%)		0/74 (0%)
Hypokalaemia	1/73 (1.4%)		0/74 (0%)
Hyponatraemia	1/73 (1.4%)		0/74 (0%)
Malnutrition NOS	0/73 (0%)		1/74 (1.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/73 (1.4%)		0/74 (0%)
Back pain	2/73 (2.7%)		0/74 (0%)
Flank pain	0/73 (0%)		1/74 (1.4%)
Osteoporosis NOS	1/73 (1.4%)		0/74 (0%)
Pain in extremity	0/73 (0%)		1/74 (1.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	3/73 (4.1%)		1/74 (1.4%)
Leukaemia NOS	0/73 (0%)		1/74 (1.4%)
Lung cancer metastatic	0/73 (0%)		1/74 (1.4%)
Malignant neoplasm progression	3/73 (4.1%)		1/74 (1.4%)
Malignant pleural effusion	1/73 (1.4%)		0/74 (0%)
Tumour haemorrhage	1/73 (1.4%)		2/74 (2.7%)
Tumour ulceration	1/73 (1.4%)		0/74 (0%)
Nervous system disorders
Anoxic encephalopathy	0/73 (0%)		1/74 (1.4%)
Cerebrovascular accident	1/73 (1.4%)		0/74 (0%)
Convulsions NOS	1/73 (1.4%)		0/74 (0%)
Dizziness	0/73 (0%)		1/74 (1.4%)
Encephalopathy	1/73 (1.4%)		0/74 (0%)
Guillain Barre syndrome	1/73 (1.4%)		0/74 (0%)
Headache	1/73 (1.4%)		0/74 (0%)
Renal and urinary disorders
Anuria	0/73 (0%)		1/74 (1.4%)
Renal colic	1/73 (1.4%)		0/74 (0%)
Renal failure NOS	0/73 (0%)		2/74 (2.7%)
Renal failure chronic	0/73 (0%)		1/74 (1.4%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	0/73 (0%)		1/74 (1.4%)
Bronchitis NOS	1/73 (1.4%)		0/74 (0%)
Chronic obstructive airways disease exacerbated	1/73 (1.4%)		0/74 (0%)
Dyspnoea	0/73 (0%)		2/74 (2.7%)
Hypoxia	0/73 (0%)		1/74 (1.4%)
Lung disorder NOS	0/73 (0%)		1/74 (1.4%)
Pleural effusion	0/73 (0%)		3/74 (4.1%)
Pneumothorax NOS	0/73 (0%)		1/74 (1.4%)
Pulmonary embolism	2/73 (2.7%)		1/74 (1.4%)
Pulmonary fibrosis	0/73 (0%)		1/74 (1.4%)
Respiratory failure	1/73 (1.4%)		1/74 (1.4%)
Skin and subcutaneous tissue disorders
Contusion	1/73 (1.4%)		0/74 (0%)
Erythema	1/73 (1.4%)		0/74 (0%)
Rash NOS	1/73 (1.4%)		0/74 (0%)
Surgical and medical procedures
Hysterectomy	1/73 (1.4%)		0/74 (0%)
Knee arthroplasty	0/73 (0%)		1/74 (1.4%)
Lung operation NOS	0/73 (0%)		1/74 (1.4%)
Operation NOS	7/73 (9.6%)		6/74 (8.1%)
Radiofrequency ablation	0/73 (0%)		1/74 (1.4%)
Tracheostomy	0/73 (0%)		1/74 (1.4%)
Vascular disorders
Aortic aneurysm rupture	0/73 (0%)		1/74 (1.4%)
Deep vein thrombosis	2/73 (2.7%)		1/74 (1.4%)
Haemorrhage NOS	0/73 (0%)		1/74 (1.4%)
Peripheral vascular disorder NOS	1/73 (1.4%)		0/74 (0%)
Petechiae	1/73 (1.4%)		0/74 (0%)
Other (Not Including Serious) Adverse Events
	Imatinib Mesylate 400 mg		Imatinib Mesylate 600 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	72/73 (98.6%)		73/74 (98.6%)
Blood and lymphatic system disorders
Anaemia NOS	12/73 (16.4%)		13/74 (17.6%)
Leukopenia NOS	4/73 (5.5%)		5/74 (6.8%)
Neutropenia	6/73 (8.2%)		7/74 (9.5%)
Eye disorders
Conjunctival haemorrhage	3/73 (4.1%)		6/74 (8.1%)
Conjunctival hyperaemia	2/73 (2.7%)		4/74 (5.4%)
Eye irritation	4/73 (5.5%)		3/74 (4.1%)
Eyelid oedema	5/73 (6.8%)		6/74 (8.1%)
Lacrimation increased	12/73 (16.4%)		13/74 (17.6%)
Vision blurred	6/73 (8.2%)		2/74 (2.7%)
Gastrointestinal disorders
Abdominal discomfort	6/73 (8.2%)		9/74 (12.2%)
Abdominal distension	7/73 (9.6%)		11/74 (14.9%)
Abdominal pain NOS	26/73 (35.6%)		25/74 (33.8%)
Abdominal pain upper	15/73 (20.5%)		11/74 (14.9%)
Constipation	7/73 (9.6%)		7/74 (9.5%)
Diarrhoea NOS	43/73 (58.9%)		51/74 (68.9%)
Dyspepsia	11/73 (15.1%)		11/74 (14.9%)
Flatulence	22/73 (30.1%)		25/74 (33.8%)
Frequent bowel movements	2/73 (2.7%)		4/74 (5.4%)
Gastrooesophageal reflux disease	4/73 (5.5%)		8/74 (10.8%)
Loose stools	9/73 (12.3%)		7/74 (9.5%)
Nausea	45/73 (61.6%)		54/74 (73%)
Vomiting NOS	27/73 (37%)		25/74 (33.8%)
General disorders
Asthenia	4/73 (5.5%)		2/74 (2.7%)
Chest pain	1/73 (1.4%)		4/74 (5.4%)
Fatigue	35/73 (47.9%)		39/74 (52.7%)
Influenza like illness	2/73 (2.7%)		4/74 (5.4%)
Lethargy	4/73 (5.5%)		3/74 (4.1%)
Oedema NOS	7/73 (9.6%)		13/74 (17.6%)
Oedema peripheral	27/73 (37%)		24/74 (32.4%)
Pain NOS	3/73 (4.1%)		7/74 (9.5%)
Pyrexia	16/73 (21.9%)		11/74 (14.9%)
Rigors	7/73 (9.6%)		5/74 (6.8%)
Infections and infestations
Gastroenteritis viral NOS	0/73 (0%)		4/74 (5.4%)
Influenza	4/73 (5.5%)		3/74 (4.1%)
Nasopharyngitis	15/73 (20.5%)		20/74 (27%)
Sinusitis NOS	4/73 (5.5%)		3/74 (4.1%)
Upper respiratory tract infection NOS	10/73 (13.7%)		13/74 (17.6%)
Urinary tract infection NOS	2/73 (2.7%)		8/74 (10.8%)
Investigations
Liver function test abnormal	4/73 (5.5%)		5/74 (6.8%)
Weight decreased	2/73 (2.7%)		4/74 (5.4%)
Metabolism and nutrition disorders
Anorexia	5/73 (6.8%)		2/74 (2.7%)
Hypokalaemia	0/73 (0%)		6/74 (8.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	7/73 (9.6%)		11/74 (14.9%)
Back pain	16/73 (21.9%)		19/74 (25.7%)
Flank pain	3/73 (4.1%)		5/74 (6.8%)
Muscle cramp	34/73 (46.6%)		43/74 (58.1%)
Myalgia	3/73 (4.1%)		5/74 (6.8%)
Pain in extremity	8/73 (11%)		9/74 (12.2%)
Nervous system disorders
Dizziness	9/73 (12.3%)		7/74 (9.5%)
Dysgeusia	2/73 (2.7%)		11/74 (14.9%)
Headache	22/73 (30.1%)		29/74 (39.2%)
Hypoaesthesia	2/73 (2.7%)		4/74 (5.4%)
Psychiatric disorders
Anxiety	8/73 (11%)		5/74 (6.8%)
Depression	4/73 (5.5%)		3/74 (4.1%)
Insomnia	14/73 (19.2%)		13/74 (17.6%)
Respiratory, thoracic and mediastinal disorders
Bronchitis NOS	4/73 (5.5%)		3/74 (4.1%)
Cough	6/73 (8.2%)		7/74 (9.5%)
Dyspnoea	5/73 (6.8%)		3/74 (4.1%)
Pharyngolaryngeal pain	9/73 (12.3%)		5/74 (6.8%)
Pleural effusion	6/73 (8.2%)		4/74 (5.4%)
Skin and subcutaneous tissue disorders
Alopecia	4/73 (5.5%)		5/74 (6.8%)
Contusion	4/73 (5.5%)		2/74 (2.7%)
Dry skin	5/73 (6.8%)		4/74 (5.4%)
Erythema	1/73 (1.4%)		4/74 (5.4%)
Face oedema	5/73 (6.8%)		8/74 (10.8%)
Periorbital oedema	39/73 (53.4%)		39/74 (52.7%)
Photosensitivity reaction NOS	0/73 (0%)		4/74 (5.4%)
Pruritus	2/73 (2.7%)		6/74 (8.1%)
Rash NOS	24/73 (32.9%)		33/74 (44.6%)
Sweating increased	4/73 (5.5%)		2/74 (2.7%)
Vascular disorders
Flushing	6/73 (8.2%)		5/74 (6.8%)

Limitations/Caveats

No safety data was collected in the extension.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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 or disclosure of trial results in their entirety.