Trial Outcomes & Findings for A Phase I/II Study of Sunitinib Malate (SU011248) In Patients With Gastrointestinal Stromal Tumor (GIST) (NCT NCT00457743)
NCT ID: NCT00457743
Last Updated: 2009-11-13
Results Overview
Dose Limiting Toxicities(DLT) in the subjects enrolled in Phase 1.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
36 participants
Primary outcome timeframe
Cycle 1 (Baseline to Week 6)
Results posted on
2009-11-13
Participant Flow
Phase 1 only included Cycle 1 for subjects enrolled in Phase 1. Phase 2 was comprised of either Cycle 2 and beyond for subjects who were enrolled in Phase 1, or all cycles for newly enrolled subjects. Additional subjects were enrolled to make a total of 30 in the recommended dose level (50-mg).
Participant milestones
| Measure |
SU-011248 25-mg
Subjects received sunitinib malate (SU-011248) at starting dose of 25-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be increased to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
SU-011248 50-mg
Subjects received sunitinib malate (SU-011248) at starting dose of 50-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
From Phase 1 part of this study, 50-mg was determined as the maximum tolerated dose and the recommended dose.
|
SU-011248 75-mg
Subjects received sunitinib malate (SU-011248) at starting dose of 75-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be reduced to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
|---|---|---|---|
|
Overall Study
STARTED
|
3
|
30
|
3
|
|
Overall Study
Enrolled in Phase 1
|
3
|
6
|
3
|
|
Overall Study
Completed Phase 1
|
3
|
6
|
3
|
|
Overall Study
Enrolled in Phase 2
|
3
|
30
|
3
|
|
Overall Study
COMPLETED
|
0
|
3
|
0
|
|
Overall Study
NOT COMPLETED
|
3
|
27
|
3
|
Reasons for withdrawal
| Measure |
SU-011248 25-mg
Subjects received sunitinib malate (SU-011248) at starting dose of 25-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be increased to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
SU-011248 50-mg
Subjects received sunitinib malate (SU-011248) at starting dose of 50-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
From Phase 1 part of this study, 50-mg was determined as the maximum tolerated dose and the recommended dose.
|
SU-011248 75-mg
Subjects received sunitinib malate (SU-011248) at starting dose of 75-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be reduced to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
4
|
0
|
|
Overall Study
Lack of Efficacy
|
3
|
23
|
3
|
Baseline Characteristics
A Phase I/II Study of Sunitinib Malate (SU011248) In Patients With Gastrointestinal Stromal Tumor (GIST)
Baseline characteristics by cohort
| Measure |
SU-011248 25-mg
n=3 Participants
Subjects received sunitinib malate (SU-011248) at starting dose of 25-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be increased to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
SU-011248 50-mg
n=30 Participants
Subjects received sunitinib malate (SU-011248) at starting dose of 50-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
From Phase 1 part of this study, 50-mg was determined as the maximum tolerated dose and the recommended dose.
|
SU-011248 75-mg
n=3 Participants
Subjects received sunitinib malate (SU-011248) at starting dose of 75-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be reduced to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
Total
n=36 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Customized
18-44 years
|
2 participants
n=5 Participants
|
2 participants
n=7 Participants
|
0 participants
n=5 Participants
|
4 participants
n=4 Participants
|
|
Age, Customized
45-64 years
|
1 participants
n=5 Participants
|
24 participants
n=7 Participants
|
1 participants
n=5 Participants
|
26 participants
n=4 Participants
|
|
Age, Customized
>=65 years
|
0 participants
n=5 Participants
|
4 participants
n=7 Participants
|
2 participants
n=5 Participants
|
6 participants
n=4 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
12 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
24 Participants
n=4 Participants
|
|
Region of Enrollment
Japan
|
3 participants
n=5 Participants
|
30 participants
n=7 Participants
|
3 participants
n=5 Participants
|
36 participants
n=4 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
0
|
3 participants
n=5 Participants
|
18 participants
n=7 Participants
|
2 participants
n=5 Participants
|
23 participants
n=4 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
1
|
0 participants
n=5 Participants
|
12 participants
n=7 Participants
|
1 participants
n=5 Participants
|
13 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Cycle 1 (Baseline to Week 6)Population: DLT analysis population consists of subjects who developed DLT or received 85% of the planned dose. One subject in 75-mg dose group was excluded from DLT analysis population because the subject received less than 85% of the planned dose.
Dose Limiting Toxicities(DLT) in the subjects enrolled in Phase 1.
Outcome measures
| Measure |
SU-011248 25-mg
n=3 Participants
Subjects received sunitinib malate (SU-011248) at starting dose of 25-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be increased to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
SU-011248 50-mg
n=6 Participants
Subjects received sunitinib malate (SU-011248) at starting dose of 50-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
From Phase 1 part of this study, 50-mg was determined as the maximum tolerated dose and the recommended dose.
|
SU-011248 75-mg
n=2 Participants
Subjects received sunitinib malate (SU-011248) at starting dose of 75-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be reduced to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
|---|---|---|---|
|
Number of Subjects With Dose Limiting Toxicities (DLT)
|
0 participants
|
0 participants
|
2 participants
|
PRIMARY outcome
Timeframe: Day 1 of Cycle 1Population: All enrolled subjects who received at least 1 dose of study medication and who had at least 1 blood concentration data for Pharmacokinetic analysis.
Maximum Plasma Concentration (Cmax) of SU-011248, its active metabolite SU-012662 and Total drug (SU-011248+SU-012662) in the subjects enrolled in Phase 1. The Cmax for total drug (SU-011248+SU-012662) was calculated as the mean of the Cmax of total drug from each individual subject (it is not the simple sum of means of Cmax of SU-011248 and SU-012662).
Outcome measures
| Measure |
SU-011248 25-mg
n=3 Participants
Subjects received sunitinib malate (SU-011248) at starting dose of 25-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be increased to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
SU-011248 50-mg
n=6 Participants
Subjects received sunitinib malate (SU-011248) at starting dose of 50-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
From Phase 1 part of this study, 50-mg was determined as the maximum tolerated dose and the recommended dose.
|
SU-011248 75-mg
n=3 Participants
Subjects received sunitinib malate (SU-011248) at starting dose of 75-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be reduced to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
|---|---|---|---|
|
Maximum Plasma Concentration (Cmax) on Cycle 1 Day 1
SU-011248
|
12.1 ng/mL
Standard Deviation 4.9
|
22.8 ng/mL
Standard Deviation 6.4
|
32.3 ng/mL
Standard Deviation 20.8
|
|
Maximum Plasma Concentration (Cmax) on Cycle 1 Day 1
SU-012662
|
1.96 ng/mL
Standard Deviation 1.27
|
4.13 ng/mL
Standard Deviation 0.93
|
4.81 ng/mL
Standard Deviation 2.54
|
|
Maximum Plasma Concentration (Cmax) on Cycle 1 Day 1
SU-011248+SU-012662
|
14.1 ng/mL
Standard Deviation 6.1
|
26.7 ng/mL
Standard Deviation 7.4
|
37.0 ng/mL
Standard Deviation 22.1
|
PRIMARY outcome
Timeframe: Day 28 of Cycle 1Population: All enrolled subjects who received at least 1 dose of study medication and who had at least 1 blood concentration data for Pharmacokinetic analysis. 3 subjects in 75mg dose group discontinued before Cycle 1 Day 28, therefore no data presented.
Maximum Plasma Concentration (Cmax) of SU-011248, its active metabolite SU-012662 and Total drug (SU-011248+SU-012662) in the subjects enrolled in Phase 1. The Cmax for total drug (SU-011248+SU-012662) was calculated as the mean of the Cmax of total drug from each individual subject (it is not the simple sum of means of Cmax of SU-011248 and SU-012662).
Outcome measures
| Measure |
SU-011248 25-mg
n=3 Participants
Subjects received sunitinib malate (SU-011248) at starting dose of 25-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be increased to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
SU-011248 50-mg
n=6 Participants
Subjects received sunitinib malate (SU-011248) at starting dose of 50-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
From Phase 1 part of this study, 50-mg was determined as the maximum tolerated dose and the recommended dose.
|
SU-011248 75-mg
Subjects received sunitinib malate (SU-011248) at starting dose of 75-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be reduced to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
|---|---|---|---|
|
Maximum Plasma Concentration (Cmax) on Cycle 1 Day 28
SU-011248
|
39.5 ng/mL
Standard Deviation 25.0
|
69.3 ng/mL
Standard Deviation 18.9
|
—
|
|
Maximum Plasma Concentration (Cmax) on Cycle 1 Day 28
SU-012662
|
15.2 ng/mL
Standard Deviation 10.2
|
38.8 ng/mL
Standard Deviation 16.0
|
—
|
|
Maximum Plasma Concentration (Cmax) on Cycle 1 Day 28
SU-011248+SU-012662
|
54.0 ng/mL
Standard Deviation 32.2
|
105 ng/mL
Standard Deviation 35
|
—
|
PRIMARY outcome
Timeframe: Day 1 of Cycle 1Population: All enrolled subjects who received at least 1 dose of study medication and who had at least 1 blood concentration data for Pharmacokinetic analysis.
Area Under the Plasma Concentration Curve (AUC0-24) of SU-011248, its active metabolite SU-012662 and Total drug (SU-011248+SU-012662) in the subjects enrolled in Phase 1. The AUC0-24 for total drug (SU-011248+SU-012662) was calculated as the mean of the AUC0-24 of total drug from each individual subject (it is not the simple sum of means of AUC0-24 of SU-011248 and SU-012662).
Outcome measures
| Measure |
SU-011248 25-mg
n=3 Participants
Subjects received sunitinib malate (SU-011248) at starting dose of 25-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be increased to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
SU-011248 50-mg
n=6 Participants
Subjects received sunitinib malate (SU-011248) at starting dose of 50-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
From Phase 1 part of this study, 50-mg was determined as the maximum tolerated dose and the recommended dose.
|
SU-011248 75-mg
n=3 Participants
Subjects received sunitinib malate (SU-011248) at starting dose of 75-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be reduced to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
|---|---|---|---|
|
Area Under the Plasma Concentration Curve (AUC0-24) on Cycle 1 Day 1
SU-011248
|
199 ng•h/mL
Standard Deviation 89
|
374 ng•h/mL
Standard Deviation 69
|
508 ng•h/mL
Standard Deviation 259
|
|
Area Under the Plasma Concentration Curve (AUC0-24) on Cycle 1 Day 1
SU-012662
|
30.9 ng•h/mL
Standard Deviation 20.6
|
70.0 ng•h/mL
Standard Deviation 14.4
|
91.1 ng•h/mL
Standard Deviation 45.3
|
|
Area Under the Plasma Concentration Curve (AUC0-24) on Cycle 1 Day 1
SU-011248+SU-012662
|
230 ng•h/mL
Standard Deviation 108
|
444 ng•h/mL
Standard Deviation 82
|
599 ng•h/mL
Standard Deviation 287
|
PRIMARY outcome
Timeframe: Day 28 of Cycle 1Population: All enrolled subjects who received at least 1 dose of study medication and who had at least 1 blood concentration data for Pharmacokinetic analysis. 3 subjects in 75-mg dose group discontinued the dose on Cycle1, therefore no data showed.
Area Under the Plasma Concentration Curve (AUC0-24) of SU-011248, its active metabolite SU-012662 and Total drug (SU-011248+SU-012662) in the subjects enrolled in Phase 1. The AUC0-24 for total drug (SU-011248+SU-012662) was calculated as the mean of the AUC0-24 of total drug from each individual subject (it is not the simple sum of means of AUC0-24 of SU-011248 and SU-012662).
Outcome measures
| Measure |
SU-011248 25-mg
n=3 Participants
Subjects received sunitinib malate (SU-011248) at starting dose of 25-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be increased to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
SU-011248 50-mg
n=6 Participants
Subjects received sunitinib malate (SU-011248) at starting dose of 50-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
From Phase 1 part of this study, 50-mg was determined as the maximum tolerated dose and the recommended dose.
|
SU-011248 75-mg
Subjects received sunitinib malate (SU-011248) at starting dose of 75-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be reduced to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
|---|---|---|---|
|
Area Under the Plasma Concentration Curve (AUC0-24) on Cycle 1 Day 28
SU-011248
|
858 ng•h/mL
Standard Deviation 600
|
1406 ng•h/mL
Standard Deviation 364
|
—
|
|
Area Under the Plasma Concentration Curve (AUC0-24) on Cycle 1 Day 28
SU-012662
|
324 ng•h/mL
Standard Deviation 223
|
772 ng•h/mL
Standard Deviation 358
|
—
|
|
Area Under the Plasma Concentration Curve (AUC0-24) on Cycle 1 Day 28
SU-011248+SU-012662
|
1182 ng•h/mL
Standard Deviation 734
|
2178 ng•h/mL
Standard Deviation 702
|
—
|
PRIMARY outcome
Timeframe: Day 1 of Cycle 1Population: All enrolled subjects who received at least 1 dose of study medication and who had at least 1 blood concentration data for Pharmacokinetic analysis.
Time to First Occurrence of Cmax (Tmax) of SU-011248, its active metabolite SU-012662 and Total drug (SU-011248+SU-012662) in the subjects enrolled in Phase 1. The Tmax for total drug (SU-011248+SU-012662) was calculated as the median of the Tmax of total drug from each individual subject (it is not the simple sum of median of Tmax of SU-011248 and SU-012662).
Outcome measures
| Measure |
SU-011248 25-mg
n=3 Participants
Subjects received sunitinib malate (SU-011248) at starting dose of 25-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be increased to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
SU-011248 50-mg
n=6 Participants
Subjects received sunitinib malate (SU-011248) at starting dose of 50-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
From Phase 1 part of this study, 50-mg was determined as the maximum tolerated dose and the recommended dose.
|
SU-011248 75-mg
n=3 Participants
Subjects received sunitinib malate (SU-011248) at starting dose of 75-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be reduced to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
|---|---|---|---|
|
Time to First Occurrence of Cmax (Tmax) on Cycle 1 Day 1
SU-011248
|
6 hours
Interval 4.0 to 8.0
|
7 hours
Interval 6.0 to 24.0
|
8 hours
Interval 4.0 to 10.0
|
|
Time to First Occurrence of Cmax (Tmax) on Cycle 1 Day 1
SU-012662
|
6 hours
Interval 4.0 to 8.0
|
9 hours
Interval 6.0 to 24.0
|
10 hours
Interval 4.0 to 10.0
|
|
Time to First Occurrence of Cmax (Tmax) on Cycle 1 Day 1
SU-011248+SU-012662
|
6 hours
Interval 4.0 to 8.0
|
7 hours
Interval 6.0 to 24.0
|
8 hours
Interval 4.0 to 10.0
|
PRIMARY outcome
Timeframe: Day 28 of Cycle 1Population: All enrolled subjects who received at least 1 dose of study medication and who had at least 1 blood concentration data for Pharmacokinetic analysis. 3 subjects in 75-mg dose group discontinued before Cycle 1 Day 28, therefore no data presented.
Time to First Occurrence of Cmax (Tmax) of SU-011248, its active metabolite SU-012662 and Total drug (SU-011248+SU-012662) in the subjects enrolled in Phase 1. The Tmax for total drug (SU-011248+SU-012662) was calculated as the median of the Tmax of total drug from each individual subject (it is not the simple sum of medians of Tmax of SU-011248 and SU-012662).
Outcome measures
| Measure |
SU-011248 25-mg
n=3 Participants
Subjects received sunitinib malate (SU-011248) at starting dose of 25-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be increased to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
SU-011248 50-mg
n=6 Participants
Subjects received sunitinib malate (SU-011248) at starting dose of 50-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
From Phase 1 part of this study, 50-mg was determined as the maximum tolerated dose and the recommended dose.
|
SU-011248 75-mg
Subjects received sunitinib malate (SU-011248) at starting dose of 75-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be reduced to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
|---|---|---|---|
|
Time to First Occurrence of Cmax (Tmax) on Cycle 1 Day 28
SU-011248
|
10 hours
Interval 6.0 to 10.0
|
6 hours
Interval 1.0 to 24.0
|
—
|
|
Time to First Occurrence of Cmax (Tmax) on Cycle 1 Day 28
SU-012662
|
4 hours
Interval 2.0 to 8.0
|
2.5 hours
Interval 0.0 to 48.0
|
—
|
|
Time to First Occurrence of Cmax (Tmax) on Cycle 1 Day 28
SU-011248+SU-012662
|
6 hours
Interval 4.0 to 8.0
|
6 hours
Interval 0.0 to 24.0
|
—
|
PRIMARY outcome
Timeframe: Day 28 of Cycle 1Population: All enrolled subjects who received at least 1 dose of study medication and who had at least 1 blood concentration data for Pharmacokinetic analysis. 3 subjects in 75-mg dose group discontinued before Cycle 1 Day 28, therefore no data presented.
SU-011248 Clearance in the subjects enrolled in Phase 1. Clearance was calculated by dividing a SU-011248 dose(mg) by AUC0-24(ng•h/mL).
Outcome measures
| Measure |
SU-011248 25-mg
n=3 Participants
Subjects received sunitinib malate (SU-011248) at starting dose of 25-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be increased to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
SU-011248 50-mg
n=6 Participants
Subjects received sunitinib malate (SU-011248) at starting dose of 50-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
From Phase 1 part of this study, 50-mg was determined as the maximum tolerated dose and the recommended dose.
|
SU-011248 75-mg
Subjects received sunitinib malate (SU-011248) at starting dose of 75-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be reduced to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
|---|---|---|---|
|
SU-011248 Clearance on Cycle 1 Day 28
|
43.1 L/h
Standard Deviation 32.8
|
38.1 L/h
Standard Deviation 11.6
|
—
|
PRIMARY outcome
Timeframe: Day 28 of Cycle 1Population: All enrolled subjects who received at least 1 dose of study medication and who had at least 1 blood concentration data for Pharmacokinetic analysis. 3 subjects in 75-mg dose group discontinued before Cycle 1 Day 28, therefore no data presented.
Accumulation Ratio (Rac) of SU-011248, its active metabolite SU-012662 and Total drug (SU-011248+SU-012662) on Cycle 1 Day 28 in the subjects enrolled in Phase 1. Rac was the ratio of Day 28 to Day 1.
Outcome measures
| Measure |
SU-011248 25-mg
n=3 Participants
Subjects received sunitinib malate (SU-011248) at starting dose of 25-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be increased to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
SU-011248 50-mg
n=6 Participants
Subjects received sunitinib malate (SU-011248) at starting dose of 50-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
From Phase 1 part of this study, 50-mg was determined as the maximum tolerated dose and the recommended dose.
|
SU-011248 75-mg
Subjects received sunitinib malate (SU-011248) at starting dose of 75-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be reduced to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
|---|---|---|---|
|
Accumulation Ratio (Rac) on Cycle 1 Day 28
SU-011248: Rac Cmax
|
3.32 ratio
Standard Deviation 2.17
|
3.10 ratio
Standard Deviation 0.77
|
—
|
|
Accumulation Ratio (Rac) on Cycle 1 Day 28
SU-011248: Rac AUC0-24
|
4.31 ratio
Standard Deviation 2.65
|
3.76 ratio
Standard Deviation 0.82
|
—
|
|
Accumulation Ratio (Rac) on Cycle 1 Day 28
SU-012662: Rac Cmax
|
7.98 ratio
Standard Deviation 4.91
|
9.00 ratio
Standard Deviation 2.20
|
—
|
|
Accumulation Ratio (Rac) on Cycle 1 Day 28
SU-012662: Rac AUC0-24
|
10.4 ratio
Standard Deviation 5.5
|
10.6 ratio
Standard Deviation 3.5
|
—
|
|
Accumulation Ratio (Rac) on Cycle 1 Day 28
SU-011248+SU-012662: Rac Cmax
|
3.87 ratio
Standard Deviation 2.36
|
3.93 ratio
Standard Deviation 0.98
|
—
|
|
Accumulation Ratio (Rac) on Cycle 1 Day 28
SU-011248+SU-012662: Rac AUC0-24
|
5.08 ratio
Standard Deviation 2.74
|
4.85 ratio
Standard Deviation 1.20
|
—
|
PRIMARY outcome
Timeframe: Day 28 of Cycles 1-4Population: Intent-to-Treat (ITT) population defined as all subjects enrolled in study that receive at least 1 dose of study medication.
Clinical Benefit Response is defined as sum of subjects confirmed with complete response (CR), partial response (PR), or stable disease (SD)\>= 22 weeks on study according to Response Evaluation Criteria in Solid Tumors (RECIST).
Outcome measures
| Measure |
SU-011248 25-mg
n=30 Participants
Subjects received sunitinib malate (SU-011248) at starting dose of 25-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be increased to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
SU-011248 50-mg
Subjects received sunitinib malate (SU-011248) at starting dose of 50-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
From Phase 1 part of this study, 50-mg was determined as the maximum tolerated dose and the recommended dose.
|
SU-011248 75-mg
Subjects received sunitinib malate (SU-011248) at starting dose of 75-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be reduced to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
|---|---|---|---|
|
Number of Subjects With Clinical Benefit Response (CBR) Based on the Extramural Review Committee Assessment in Recommended Dose Group
Total Number of Subjects with CR+PR+SD>=22weeks
|
12 participants
|
—
|
—
|
|
Number of Subjects With Clinical Benefit Response (CBR) Based on the Extramural Review Committee Assessment in Recommended Dose Group
Complete Response (CR)
|
0 participants
|
—
|
—
|
|
Number of Subjects With Clinical Benefit Response (CBR) Based on the Extramural Review Committee Assessment in Recommended Dose Group
Partial Response (PR)
|
4 participants
|
—
|
—
|
|
Number of Subjects With Clinical Benefit Response (CBR) Based on the Extramural Review Committee Assessment in Recommended Dose Group
Stable Disease (SD) >= 22 weeks
|
8 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1, 14, 28 of Cycles 1-4Population: All enrolled subjects who received at least 1 dose of study medication and who had at least 1 blood concentration data for Pharmacodynamics analysis. n= Number of subjects with analyzable data.
Plasma concentrations of potential pharmacodynamic markers; Vascular Endothelial Growth Factor (VEGF)
Outcome measures
| Measure |
SU-011248 25-mg
n=30 Participants
Subjects received sunitinib malate (SU-011248) at starting dose of 25-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be increased to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
SU-011248 50-mg
Subjects received sunitinib malate (SU-011248) at starting dose of 50-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
From Phase 1 part of this study, 50-mg was determined as the maximum tolerated dose and the recommended dose.
|
SU-011248 75-mg
Subjects received sunitinib malate (SU-011248) at starting dose of 75-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be reduced to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
|---|---|---|---|
|
Plasma Concentrations of Vascular Endothelial Growth Factor (VEGF)
Cycle 1 Day 1 (n=30)
|
55.30 pg/mL
Standard Deviation 32.43
|
—
|
—
|
|
Plasma Concentrations of Vascular Endothelial Growth Factor (VEGF)
Cycle 1 Day 14 (n=30)
|
179.94 pg/mL
Standard Deviation 116.00
|
—
|
—
|
|
Plasma Concentrations of Vascular Endothelial Growth Factor (VEGF)
Cycle 1 Day 28 (n=19)
|
192.42 pg/mL
Standard Deviation 210.58
|
—
|
—
|
|
Plasma Concentrations of Vascular Endothelial Growth Factor (VEGF)
Cycle 2 Day 1 (n=26)
|
62.05 pg/mL
Standard Deviation 38.20
|
—
|
—
|
|
Plasma Concentrations of Vascular Endothelial Growth Factor (VEGF)
Cycle 2 Day 14 (n=24)
|
173.12 pg/mL
Standard Deviation 96.30
|
—
|
—
|
|
Plasma Concentrations of Vascular Endothelial Growth Factor (VEGF)
Cycle 2 Day 28 (n=20)
|
207.79 pg/mL
Standard Deviation 158.05
|
—
|
—
|
|
Plasma Concentrations of Vascular Endothelial Growth Factor (VEGF)
Cycle 3 Day 1 (n=18)
|
58.80 pg/mL
Standard Deviation 26.13
|
—
|
—
|
|
Plasma Concentrations of Vascular Endothelial Growth Factor (VEGF)
Cycle 3 Day 14 (n=19)
|
208.93 pg/mL
Standard Deviation 159.41
|
—
|
—
|
|
Plasma Concentrations of Vascular Endothelial Growth Factor (VEGF)
Cycle 3 Day 28 (n=13)
|
238.74 pg/mL
Standard Deviation 227.63
|
—
|
—
|
|
Plasma Concentrations of Vascular Endothelial Growth Factor (VEGF)
Cycle 4 Day 1 (n=11)
|
54.83 pg/mL
Standard Deviation 14.86
|
—
|
—
|
|
Plasma Concentrations of Vascular Endothelial Growth Factor (VEGF)
Cycle 4 Day 14 (n=12)
|
227.28 pg/mL
Standard Deviation 163.52
|
—
|
—
|
|
Plasma Concentrations of Vascular Endothelial Growth Factor (VEGF)
Cycle 4 Day 28 (n=9)
|
343.21 pg/mL
Standard Deviation 210.28
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1, 14, 28 of Cycles 1-4Population: All enrolled subjects who received at least 1 dose of study medication and who had at least 1 blood concentration data for Pharmacodynamics analysis. n= Number of subjects with analyzable data.
Plasma concentrations of potential pharmacodynamic markers; Soluble Vascular Endothelial Growth Factor Type 2 Receptors (sVEGFR2)
Outcome measures
| Measure |
SU-011248 25-mg
n=30 Participants
Subjects received sunitinib malate (SU-011248) at starting dose of 25-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be increased to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
SU-011248 50-mg
Subjects received sunitinib malate (SU-011248) at starting dose of 50-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
From Phase 1 part of this study, 50-mg was determined as the maximum tolerated dose and the recommended dose.
|
SU-011248 75-mg
Subjects received sunitinib malate (SU-011248) at starting dose of 75-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be reduced to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
|---|---|---|---|
|
Plasma Concentrations of Soluble Vascular Endothelial Growth Factor Type 2 Receptors (sVEGFR2)
Cycle 1 Day 1 (n=30)
|
8740.20 pg/mL
Standard Deviation 1702.84
|
—
|
—
|
|
Plasma Concentrations of Soluble Vascular Endothelial Growth Factor Type 2 Receptors (sVEGFR2)
Cycle 1 Day 14 (n=30)
|
5721.98 pg/mL
Standard Deviation 1136.89
|
—
|
—
|
|
Plasma Concentrations of Soluble Vascular Endothelial Growth Factor Type 2 Receptors (sVEGFR2)
Cycle 1 Day 28 (n=19)
|
5082.92 pg/mL
Standard Deviation 1449.26
|
—
|
—
|
|
Plasma Concentrations of Soluble Vascular Endothelial Growth Factor Type 2 Receptors (sVEGFR2)
Cycle 2 Day 1 (n=26)
|
7579.98 pg/mL
Standard Deviation 1844.58
|
—
|
—
|
|
Plasma Concentrations of Soluble Vascular Endothelial Growth Factor Type 2 Receptors (sVEGFR2)
Cycle 2 Day 14 (n=24)
|
5808.08 pg/mL
Standard Deviation 1484.30
|
—
|
—
|
|
Plasma Concentrations of Soluble Vascular Endothelial Growth Factor Type 2 Receptors (sVEGFR2)
Cycle 2 Day 28 (n=20)
|
4770.15 pg/mL
Standard Deviation 1311.88
|
—
|
—
|
|
Plasma Concentrations of Soluble Vascular Endothelial Growth Factor Type 2 Receptors (sVEGFR2)
Cycle 3 Day 1 (n=18)
|
6802.86 pg/mL
Standard Deviation 1641.46
|
—
|
—
|
|
Plasma Concentrations of Soluble Vascular Endothelial Growth Factor Type 2 Receptors (sVEGFR2)
Cycle 3 Day 14 (n=19)
|
5022.84 pg/mL
Standard Deviation 1192.52
|
—
|
—
|
|
Plasma Concentrations of Soluble Vascular Endothelial Growth Factor Type 2 Receptors (sVEGFR2)
Cycle 3 Day 28 (n=13)
|
4297.91 pg/mL
Standard Deviation 1157.62
|
—
|
—
|
|
Plasma Concentrations of Soluble Vascular Endothelial Growth Factor Type 2 Receptors (sVEGFR2)
Cycle 4 Day 1 (n=11)
|
6559.50 pg/mL
Standard Deviation 1152.24
|
—
|
—
|
|
Plasma Concentrations of Soluble Vascular Endothelial Growth Factor Type 2 Receptors (sVEGFR2)
Cycle 4 Day 14 (n=12)
|
5038.50 pg/mL
Standard Deviation 1078.45
|
—
|
—
|
|
Plasma Concentrations of Soluble Vascular Endothelial Growth Factor Type 2 Receptors (sVEGFR2)
Cycle 4 Day 28 (n=9)
|
4142.72 pg/mL
Standard Deviation 1103.29
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1, 14, 28 of Cycles 1-4Population: All enrolled subjects who received at least 1 dose of study medication and who had at least 1 blood concentration data for Pharmacodynamics analysis. n= Number of subjects with analyzable data.
Plasma concentrations of potential pharmacodynamic markers; Soluble Stem Cell Factor Receptor (sKIT)
Outcome measures
| Measure |
SU-011248 25-mg
n=30 Participants
Subjects received sunitinib malate (SU-011248) at starting dose of 25-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be increased to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
SU-011248 50-mg
Subjects received sunitinib malate (SU-011248) at starting dose of 50-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
From Phase 1 part of this study, 50-mg was determined as the maximum tolerated dose and the recommended dose.
|
SU-011248 75-mg
Subjects received sunitinib malate (SU-011248) at starting dose of 75-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be reduced to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
|---|---|---|---|
|
Plasma Concentrations of Soluble Stem Cell Factor Receptor (sKIT)
Cycle 1 Day 1 (n=30)
|
48237.33 pg/mL
Standard Deviation 56643.93
|
—
|
—
|
|
Plasma Concentrations of Soluble Stem Cell Factor Receptor (sKIT)
Cycle 1 Day 14 (n=30)
|
53087.75 pg/mL
Standard Deviation 71243.85
|
—
|
—
|
|
Plasma Concentrations of Soluble Stem Cell Factor Receptor (sKIT)
Cycle 1 Day 28 (n=19)
|
35538.95 pg/mL
Standard Deviation 16082.33
|
—
|
—
|
|
Plasma Concentrations of Soluble Stem Cell Factor Receptor (sKIT)
Cycle 2 Day 1 (n=26)
|
39011.35 pg/mL
Standard Deviation 38304.60
|
—
|
—
|
|
Plasma Concentrations of Soluble Stem Cell Factor Receptor (sKIT)
Cycle 2 Day 14 (n=24)
|
40432.29 pg/mL
Standard Deviation 45085.57
|
—
|
—
|
|
Plasma Concentrations of Soluble Stem Cell Factor Receptor (sKIT)
Cycle 2 Day 28 (n=20)
|
30715.75 pg/mL
Standard Deviation 16212.04
|
—
|
—
|
|
Plasma Concentrations of Soluble Stem Cell Factor Receptor (sKIT)
Cycle 3 Day 1 (n=18)
|
27814.17 pg/mL
Standard Deviation 10362.85
|
—
|
—
|
|
Plasma Concentrations of Soluble Stem Cell Factor Receptor (sKIT)
Cycle 3 Day 14 (n=19)
|
32973.68 pg/mL
Standard Deviation 14483.42
|
—
|
—
|
|
Plasma Concentrations of Soluble Stem Cell Factor Receptor (sKIT)
Cycle 3 Day 28 (n=13)
|
32760.77 pg/mL
Standard Deviation 16888.75
|
—
|
—
|
|
Plasma Concentrations of Soluble Stem Cell Factor Receptor (sKIT)
Cycle 4 Day 1 (n=11)
|
28961.82 pg/mL
Standard Deviation 14899.42
|
—
|
—
|
|
Plasma Concentrations of Soluble Stem Cell Factor Receptor (sKIT)
Cycle 4 Day 14 (n=12)
|
32265.83 pg/mL
Standard Deviation 16143.54
|
—
|
—
|
|
Plasma Concentrations of Soluble Stem Cell Factor Receptor (sKIT)
Cycle 4 Day 28 (n=9)
|
32571.11 pg/mL
Standard Deviation 20949.63
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 14, 28 of Cycle 1; Day 1, 14, 28 of Cycles 2-4Population: All enrolled subjects who received at least 1 dose of study medication and who had at least 1 blood concentration data for Pharmacokinetic analysis. n= Number of subjects with analyzable data.
Trough Plasma Concentration (Ctrough) means the concentration prior to study drug administration
Outcome measures
| Measure |
SU-011248 25-mg
n=30 Participants
Subjects received sunitinib malate (SU-011248) at starting dose of 25-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be increased to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
SU-011248 50-mg
Subjects received sunitinib malate (SU-011248) at starting dose of 50-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
From Phase 1 part of this study, 50-mg was determined as the maximum tolerated dose and the recommended dose.
|
SU-011248 75-mg
Subjects received sunitinib malate (SU-011248) at starting dose of 75-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be reduced to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
|---|---|---|---|
|
Trough Plasma Concentration (Ctrough) of SU-011248
Cycle 1 Day 14 (n=28)
|
58.93 ng/mL
Standard Deviation 23.87
|
—
|
—
|
|
Trough Plasma Concentration (Ctrough) of SU-011248
Cycle 1 Day 28 (n=18)
|
44.52 ng/mL
Standard Deviation 15.45
|
—
|
—
|
|
Trough Plasma Concentration (Ctrough) of SU-011248
Cycle 2 Day 1 (n=15)
|
1.17 ng/mL
Standard Deviation 0.60
|
—
|
—
|
|
Trough Plasma Concentration (Ctrough) of SU-011248
Cycle 2 Day 14 (n=23)
|
51.23 ng/mL
Standard Deviation 16.98
|
—
|
—
|
|
Trough Plasma Concentration (Ctrough) of SU-011248
Cycle 2 Day 28 (n=20)
|
48.09 ng/mL
Standard Deviation 22.41
|
—
|
—
|
|
Trough Plasma Concentration (Ctrough) of SU-011248
Cycle 3 Day 1 (n=11)
|
1.62 ng/mL
Standard Deviation 0.88
|
—
|
—
|
|
Trough Plasma Concentration (Ctrough) of SU-011248
Cycle 3 Day 14 (n=14)
|
58.72 ng/mL
Standard Deviation 27.09
|
—
|
—
|
|
Trough Plasma Concentration (Ctrough) of SU-011248
Cycle 3 Day 28 (n=10)
|
47.13 ng/mL
Standard Deviation 21.73
|
—
|
—
|
|
Trough Plasma Concentration (Ctrough) of SU-011248
Cycle 4 Day 1 (n=5)
|
1.52 ng/mL
Standard Deviation 0.81
|
—
|
—
|
|
Trough Plasma Concentration (Ctrough) of SU-011248
Cycle 4 Day 14 (n=7)
|
46.13 ng/mL
Standard Deviation 22.28
|
—
|
—
|
|
Trough Plasma Concentration (Ctrough) of SU-011248
Cycle 4 Day 28 (n=8)
|
47.33 ng/mL
Standard Deviation 12.95
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 14, 28 of Cycle 1; Day 1, 14, 28 of Cycles 2-4Population: All enrolled subjects who received at least 1 dose of study medication and who had at least 1 blood concentration data for Pharmacokinetic analysis. n= Number of subjects with analyzable data.
Trough Plasma Concentration (Ctrough) means the concentration prior to study drug administration
Outcome measures
| Measure |
SU-011248 25-mg
n=30 Participants
Subjects received sunitinib malate (SU-011248) at starting dose of 25-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be increased to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
SU-011248 50-mg
Subjects received sunitinib malate (SU-011248) at starting dose of 50-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
From Phase 1 part of this study, 50-mg was determined as the maximum tolerated dose and the recommended dose.
|
SU-011248 75-mg
Subjects received sunitinib malate (SU-011248) at starting dose of 75-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be reduced to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
|---|---|---|---|
|
Trough Plasma Concentration (Ctrough) of SU-012262
Cycle 1 Day 14 (n=28)
|
26.41 ng/mL
Standard Deviation 15.86
|
—
|
—
|
|
Trough Plasma Concentration (Ctrough) of SU-012262
Cycle 1 Day 28 (n=18)
|
24.52 ng/mL
Standard Deviation 13.28
|
—
|
—
|
|
Trough Plasma Concentration (Ctrough) of SU-012262
Cycle 2 Day 1 (n=15)
|
2.01 ng/mL
Standard Deviation 0.90
|
—
|
—
|
|
Trough Plasma Concentration (Ctrough) of SU-012262
Cycle 2 Day 14 (n=23)
|
24.06 ng/mL
Standard Deviation 11.54
|
—
|
—
|
|
Trough Plasma Concentration (Ctrough) of SU-012262
Cycle 2 Day 28 (n=20)
|
24.47 ng/mL
Standard Deviation 14.92
|
—
|
—
|
|
Trough Plasma Concentration (Ctrough) of SU-012262
Cycle 3 Day 1 (n=11)
|
2.26 ng/mL
Standard Deviation 1.20
|
—
|
—
|
|
Trough Plasma Concentration (Ctrough) of SU-012262
Cycle 3 Day 14 (n=14)
|
27.69 ng/mL
Standard Deviation 16.34
|
—
|
—
|
|
Trough Plasma Concentration (Ctrough) of SU-012262
Cycle 3 Day 28 (n=10)
|
23.83 ng/mL
Standard Deviation 12.59
|
—
|
—
|
|
Trough Plasma Concentration (Ctrough) of SU-012262
Cycle 4 Day 1 (n=5)
|
2.02 ng/mL
Standard Deviation 0.90
|
—
|
—
|
|
Trough Plasma Concentration (Ctrough) of SU-012262
Cycle 4 Day 14 (n=7)
|
19.86 ng/mL
Standard Deviation 11.38
|
—
|
—
|
|
Trough Plasma Concentration (Ctrough) of SU-012262
Cycle 4 Day 28 (n=8)
|
25.94 ng/mL
Standard Deviation 12.28
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 14, 28 of Cycle 1; Day 1, 14, 28 of Cycles 2-4Population: All enrolled subjects who received at least 1 dose of study medication and who had at least 1 blood concentration data for Pharmacokinetic analysis. n= Number of subjects with analyzable data.
Trough Plasma Concentration (Ctrough) means the concentration prior to study drug administration
Outcome measures
| Measure |
SU-011248 25-mg
n=30 Participants
Subjects received sunitinib malate (SU-011248) at starting dose of 25-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be increased to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
SU-011248 50-mg
Subjects received sunitinib malate (SU-011248) at starting dose of 50-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
From Phase 1 part of this study, 50-mg was determined as the maximum tolerated dose and the recommended dose.
|
SU-011248 75-mg
Subjects received sunitinib malate (SU-011248) at starting dose of 75-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be reduced to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
|---|---|---|---|
|
Trough Plasma Concentration (Ctrough) of SU-011248+SU-012662
Cycle 1 Day 14 (n=28)
|
85.33 ng/mL
Standard Deviation 36.59
|
—
|
—
|
|
Trough Plasma Concentration (Ctrough) of SU-011248+SU-012662
Cycle 1 Day 28 (n=18)
|
69.05 ng/mL
Standard Deviation 27.52
|
—
|
—
|
|
Trough Plasma Concentration (Ctrough) of SU-011248+SU-012662
Cycle 2 Day 1 (n=15)
|
3.18 ng/mL
Standard Deviation 1.45
|
—
|
—
|
|
Trough Plasma Concentration (Ctrough) of SU-011248+SU-012662
Cycle 2 Day 14 (n=23)
|
75.29 ng/mL
Standard Deviation 27.35
|
—
|
—
|
|
Trough Plasma Concentration (Ctrough) of SU-011248+SU-012662
Cycle 2 Day 28 (n=20)
|
72.56 ng/mL
Standard Deviation 36.14
|
—
|
—
|
|
Trough Plasma Concentration (Ctrough) of SU-011248+SU-012662
Cycle 3 Day 1 (n=11)
|
3.88 ng/mL
Standard Deviation 1.88
|
—
|
—
|
|
Trough Plasma Concentration (Ctrough) of SU-011248+SU-012662
Cycle 3 Day 14 (n=14)
|
86.41 ng/mL
Standard Deviation 42.83
|
—
|
—
|
|
Trough Plasma Concentration (Ctrough) of SU-011248+SU-012662
Cycle 3 Day 28 (n=10)
|
70.96 ng/mL
Standard Deviation 32.81
|
—
|
—
|
|
Trough Plasma Concentration (Ctrough) of SU-011248+SU-012662
Cycle 4 Day 1 (n=5)
|
3.54 ng/mL
Standard Deviation 1.46
|
—
|
—
|
|
Trough Plasma Concentration (Ctrough) of SU-011248+SU-012662
Cycle 4 Day 14 (n=7)
|
65.99 ng/mL
Standard Deviation 33.42
|
—
|
—
|
|
Trough Plasma Concentration (Ctrough) of SU-011248+SU-012662
Cycle 4 Day 28 (n=8)
|
73.26 ng/mL
Standard Deviation 24.82
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 7, 14, 28, 35 of Cycle 1; Day 1, 7, 14, 28, 35 of Cycles 2-4Population: Intent-to-Treat (ITT) population defined as all subjects enrolled in study that receive at least 1 dose of study medication. n= Number of subjects with analyzable data.
Patient-reported outcome: Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) questionnaires (version 4A). The questionnaire consists of a 13-item subscale which covers specific fatigue questions. The subject rates the intensity of fatigue and its related symptoms on a five-point scale(0 to 4). High score is indicating low fatigue. The total score of the 13 items was evaluated. Change from Baseline: Score at each observation minus score at baseline
Outcome measures
| Measure |
SU-011248 25-mg
n=30 Participants
Subjects received sunitinib malate (SU-011248) at starting dose of 25-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be increased to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
SU-011248 50-mg
Subjects received sunitinib malate (SU-011248) at starting dose of 50-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
From Phase 1 part of this study, 50-mg was determined as the maximum tolerated dose and the recommended dose.
|
SU-011248 75-mg
Subjects received sunitinib malate (SU-011248) at starting dose of 75-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be reduced to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
|---|---|---|---|
|
Changes From Baseline of Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaires
Cycle 1 Day 7 (n=30)
|
1.0 scores on a scale
Standard Deviation 5.6
|
—
|
—
|
|
Changes From Baseline of Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaires
Cycle 1 Day 14 (n=30)
|
-2.3 scores on a scale
Standard Deviation 7.8
|
—
|
—
|
|
Changes From Baseline of Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaires
Cycle 1 Day 21 (n=30)
|
-6.3 scores on a scale
Standard Deviation 13.8
|
—
|
—
|
|
Changes From Baseline of Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaires
Cycle 1 Day 28 (n=30)
|
-4.6 scores on a scale
Standard Deviation 10.2
|
—
|
—
|
|
Changes From Baseline of Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaires
Cycle 1 Day 35 (n=30)
|
-0.4 scores on a scale
Standard Deviation 6.6
|
—
|
—
|
|
Changes From Baseline of Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaires
Cycle 2 Day 1 (n=30)
|
1.5 scores on a scale
Standard Deviation 5.8
|
—
|
—
|
|
Changes From Baseline of Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaires
Cycle 2 Day 7 (n=30)
|
-0.2 scores on a scale
Standard Deviation 8.0
|
—
|
—
|
|
Changes From Baseline of Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaires
Cycle 2 Day 14 (n=30)
|
-1.3 scores on a scale
Standard Deviation 8.7
|
—
|
—
|
|
Changes From Baseline of Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaires
Cycle 2 Day 21 (n=30)
|
-3.6 scores on a scale
Standard Deviation 10.5
|
—
|
—
|
|
Changes From Baseline of Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaires
Cycle 2 Day 28 (n=29)
|
-5.1 scores on a scale
Standard Deviation 10.6
|
—
|
—
|
|
Changes From Baseline of Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaires
Cycle 2 Day 35 (n=29)
|
-2.5 scores on a scale
Standard Deviation 8.7
|
—
|
—
|
|
Changes From Baseline of Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaires
Cycle 3 Day 1 (n=25)
|
-1.3 scores on a scale
Standard Deviation 8.6
|
—
|
—
|
|
Changes From Baseline of Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaires
Cycle 3 Day 7 (n=24)
|
-1.2 scores on a scale
Standard Deviation 6.6
|
—
|
—
|
|
Changes From Baseline of Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaires
Cycle 3 Day 14 (n=25)
|
-1.8 scores on a scale
Standard Deviation 9.3
|
—
|
—
|
|
Changes From Baseline of Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaires
Cycle 3 Day 21 (n=24)
|
-4.8 scores on a scale
Standard Deviation 9.8
|
—
|
—
|
|
Changes From Baseline of Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaires
Cycle 3 Day 28 (n=25)
|
-3.8 scores on a scale
Standard Deviation 10.0
|
—
|
—
|
|
Changes From Baseline of Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaires
Cycle 3 Day 35 (n=25)
|
-3.4 scores on a scale
Standard Deviation 10.4
|
—
|
—
|
|
Changes From Baseline of Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaires
Cycle 4 Day 1 (n=21)
|
-2.7 scores on a scale
Standard Deviation 9.5
|
—
|
—
|
|
Changes From Baseline of Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaires
Cycle 4 Day 7 (n=20)
|
-4.4 scores on a scale
Standard Deviation 11.4
|
—
|
—
|
|
Changes From Baseline of Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaires
Cycle 4 Day 14 (n=21)
|
-6.2 scores on a scale
Standard Deviation 11.5
|
—
|
—
|
|
Changes From Baseline of Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaires
Cycle 4 Day 21 (n=20)
|
-8.8 scores on a scale
Standard Deviation 12.5
|
—
|
—
|
|
Changes From Baseline of Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaires
Cycle 4 Day 28 (n=19)
|
-9.7 scores on a scale
Standard Deviation 11.5
|
—
|
—
|
|
Changes From Baseline of Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaires
Cycle 4 Day 35 (n=20)
|
-8.6 scores on a scale
Standard Deviation 11.2
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 28 of Cycle 1; Day 1, 28 of Cycles 2-4Population: Intent-to-Treat (ITT) population defined as all subjects enrolled in study that receive at least 1 dose of study medication. n= Number of subjects with analyzable data.
The EQ-5D questionnaires evaluates 5 dimensions of health. The subjects rates the severity of impairment for each dimensions on a 3-point scale(1 to 3). The digits for five dimensions were combined in a five-digit number describing the respondent's health state. Health states were converted into a weighted health state index. High score is indicating high health. Change from Baseline: weighted health state index at each observation minus weighted health state index at baseline
Outcome measures
| Measure |
SU-011248 25-mg
n=30 Participants
Subjects received sunitinib malate (SU-011248) at starting dose of 25-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be increased to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
SU-011248 50-mg
Subjects received sunitinib malate (SU-011248) at starting dose of 50-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
From Phase 1 part of this study, 50-mg was determined as the maximum tolerated dose and the recommended dose.
|
SU-011248 75-mg
Subjects received sunitinib malate (SU-011248) at starting dose of 75-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be reduced to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
|---|---|---|---|
|
Change From Baseline of European Quality of Life Questionnaire- 5 Dimensions(EQ-5D) Questionnaires
Cycle 1 Day 28 (n=30)
|
-0.148 index scores on a scale
Standard Deviation 0.213
|
—
|
—
|
|
Change From Baseline of European Quality of Life Questionnaire- 5 Dimensions(EQ-5D) Questionnaires
Cycle 2 Day 1 (n=30)
|
-0.038 index scores on a scale
Standard Deviation 0.171
|
—
|
—
|
|
Change From Baseline of European Quality of Life Questionnaire- 5 Dimensions(EQ-5D) Questionnaires
Cycle 2 Day 28 (n=30)
|
-0.121 index scores on a scale
Standard Deviation 0.215
|
—
|
—
|
|
Change From Baseline of European Quality of Life Questionnaire- 5 Dimensions(EQ-5D) Questionnaires
Cycle 3 Day 1 (n=25)
|
-0.010 index scores on a scale
Standard Deviation 0.125
|
—
|
—
|
|
Change From Baseline of European Quality of Life Questionnaire- 5 Dimensions(EQ-5D) Questionnaires
Cycle 3 Day 28 (n=25)
|
-0.091 index scores on a scale
Standard Deviation 0.210
|
—
|
—
|
|
Change From Baseline of European Quality of Life Questionnaire- 5 Dimensions(EQ-5D) Questionnaires
Cycle 4 Day 1 (n=21)
|
-0.006 index scores on a scale
Standard Deviation 0.137
|
—
|
—
|
|
Change From Baseline of European Quality of Life Questionnaire- 5 Dimensions(EQ-5D) Questionnaires
Cycle 4 Day 28 (n=18)
|
-0.142 index scores on a scale
Standard Deviation 0.198
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 28 of Cycles 1-4Population: Intent-to-Treat (ITT) population defined as all subjects enrolled in study that receive at least 1 dose of study medication.
Number of subjects with Disease Controlled is defined as sum of the subjects confirmed with complete response (CR), partial response (PR), or stable disease (SD)\>= 10 weeks on study according to Response Evaluation Criteria in Solid Tumors (RECIST).
Outcome measures
| Measure |
SU-011248 25-mg
n=30 Participants
Subjects received sunitinib malate (SU-011248) at starting dose of 25-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be increased to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
SU-011248 50-mg
Subjects received sunitinib malate (SU-011248) at starting dose of 50-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
From Phase 1 part of this study, 50-mg was determined as the maximum tolerated dose and the recommended dose.
|
SU-011248 75-mg
Subjects received sunitinib malate (SU-011248) at starting dose of 75-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be reduced to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
|---|---|---|---|
|
Number of Subjects With Disease Controlled Based on the Extramural Review Committee Assessment in Recommended Dose Group
Total number of Subjects with CR+PR+SD>=10weeks
|
17 participants
|
—
|
—
|
|
Number of Subjects With Disease Controlled Based on the Extramural Review Committee Assessment in Recommended Dose Group
Complete Response (CR)
|
0 participants
|
—
|
—
|
|
Number of Subjects With Disease Controlled Based on the Extramural Review Committee Assessment in Recommended Dose Group
Partial Response (PR)
|
4 participants
|
—
|
—
|
|
Number of Subjects With Disease Controlled Based on the Extramural Review Committee Assessment in Recommended Dose Group
Stable Disease (SD) >= 10 weeks
|
13 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 28 of Cycles 1-4Population: ITT population defined as all subjects enrolled in study that receive at least 1 dose of study medication.
Number of subjects with Objective Response is defined as sum of the subjects confirmed with complete response (CR) and partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST).
Outcome measures
| Measure |
SU-011248 25-mg
n=30 Participants
Subjects received sunitinib malate (SU-011248) at starting dose of 25-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be increased to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
SU-011248 50-mg
Subjects received sunitinib malate (SU-011248) at starting dose of 50-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
From Phase 1 part of this study, 50-mg was determined as the maximum tolerated dose and the recommended dose.
|
SU-011248 75-mg
Subjects received sunitinib malate (SU-011248) at starting dose of 75-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be reduced to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
|---|---|---|---|
|
Number of Subjects With Objective Response Based on the Extramural Review Committee Assessment in Recommended Dose Group
Total Number of Subjects with CR+PR
|
4 participants
|
—
|
—
|
|
Number of Subjects With Objective Response Based on the Extramural Review Committee Assessment in Recommended Dose Group
Complete Response (CR)
|
0 participants
|
—
|
—
|
|
Number of Subjects With Objective Response Based on the Extramural Review Committee Assessment in Recommended Dose Group
Partial Response (PR)
|
4 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: From the first dose to Progressive DiseasePopulation: Intent-to-Treat (ITT) population defined as all subjects enrolled in study that receive at least 1 dose of study medication.
Time To tumor Progression (TTP) is defined as the time from the date of first dose of study treatment to the date of the first documentation of Progressive Disease (PD).
Outcome measures
| Measure |
SU-011248 25-mg
n=30 Participants
Subjects received sunitinib malate (SU-011248) at starting dose of 25-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be increased to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
SU-011248 50-mg
Subjects received sunitinib malate (SU-011248) at starting dose of 50-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
From Phase 1 part of this study, 50-mg was determined as the maximum tolerated dose and the recommended dose.
|
SU-011248 75-mg
Subjects received sunitinib malate (SU-011248) at starting dose of 75-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be reduced to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
|---|---|---|---|
|
Time To Tumor Progression (TTP)
|
30.3 Weeks
Interval 22.0 to 46.1
|
—
|
—
|
SECONDARY outcome
Timeframe: From the first dose to Progressive Disease or DeathPopulation: Intent-to-Treat (ITT) population defined as all subjects enrolled in study that receive at least 1 dose of study medication.
Progression-Free Survival (PFS) is defined as the time from the date of first dose of study treatment to the date of the first documentation of Progressive Disease (PD) or death.
Outcome measures
| Measure |
SU-011248 25-mg
n=30 Participants
Subjects received sunitinib malate (SU-011248) at starting dose of 25-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be increased to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
SU-011248 50-mg
Subjects received sunitinib malate (SU-011248) at starting dose of 50-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
From Phase 1 part of this study, 50-mg was determined as the maximum tolerated dose and the recommended dose.
|
SU-011248 75-mg
Subjects received sunitinib malate (SU-011248) at starting dose of 75-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be reduced to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
|---|---|---|---|
|
Progression-Free Survival (PFS)
|
30.3 Weeks
Interval 22.0 to 46.1
|
—
|
—
|
SECONDARY outcome
Timeframe: From the first dose to Progressive Disease, Treatment discontinuation except completion of treatment, or Death due to cancer.Population: Intent-to-Treat (ITT) population defined as all subjects enrolled in study that receive at least 1 dose of study medication.
Time To Failure (TTF) is defined as the time from the date of first dose of study treatment to the date of the first documentation of Progressive Disease (PD), the date of treatment discontinuation except completion of treatment, or date of death due to cancer.
Outcome measures
| Measure |
SU-011248 25-mg
n=30 Participants
Subjects received sunitinib malate (SU-011248) at starting dose of 25-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be increased to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
SU-011248 50-mg
Subjects received sunitinib malate (SU-011248) at starting dose of 50-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
From Phase 1 part of this study, 50-mg was determined as the maximum tolerated dose and the recommended dose.
|
SU-011248 75-mg
Subjects received sunitinib malate (SU-011248) at starting dose of 75-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be reduced to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
|---|---|---|---|
|
Time To Failure (TTF)
|
28.4 Weeks
Interval 21.9 to 46.1
|
—
|
—
|
SECONDARY outcome
Timeframe: From the first dose to deathPopulation: Intent-to-Treat (ITT) population defined as all subjects enrolled in study that receive at least 1 dose of study medication.
Overall Survival Time is defined as the time from the date of first dose of study treatment to the date of the death due to any cause. For subjects whose death had not been confirmed, Overall Survival Time was censored on the last date when the patient was known to be alive. Survival was surveyed once a year from the registration day of the first subject, for all the subjects who received the study drug at least once.
Outcome measures
| Measure |
SU-011248 25-mg
n=30 Participants
Subjects received sunitinib malate (SU-011248) at starting dose of 25-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be increased to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
SU-011248 50-mg
Subjects received sunitinib malate (SU-011248) at starting dose of 50-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
From Phase 1 part of this study, 50-mg was determined as the maximum tolerated dose and the recommended dose.
|
SU-011248 75-mg
Subjects received sunitinib malate (SU-011248) at starting dose of 75-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be reduced to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
|---|---|---|---|
|
Overall Survival Time
|
62.0 Weeks
Interval 47.9 to 99.9
|
—
|
—
|
Adverse Events
SU-011248 25-mg
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
SU-011248 50-mg
Serious events: 12 serious events
Other events: 30 other events
Deaths: 0 deaths
SU-011248 75-mg
Serious events: 2 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
SU-011248 25-mg
n=3 participants at risk
Subjects received sunitinib malate (SU-011248) at starting dose of 25-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be increased to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
SU-011248 50-mg
n=30 participants at risk
Subjects received sunitinib malate (SU-011248) at starting dose of 50-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
From Phase 1 part of this study, 50-mg was determined as the maximum tolerated dose and the recommended dose.
|
SU-011248 75-mg
n=3 participants at risk
Subjects received sunitinib malate (SU-011248) at starting dose of 75-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be reduced to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
|---|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
33.3%
1/3
|
0.00%
0/30
|
0.00%
0/3
|
|
Nervous system disorders
Altered state of consciousness
|
0.00%
0/3
|
3.3%
1/30
|
0.00%
0/3
|
|
Infections and infestations
Anal abscess
|
0.00%
0/3
|
0.00%
0/30
|
33.3%
1/3
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/3
|
0.00%
0/30
|
33.3%
1/3
|
|
Cardiac disorders
Cardiomyopathy
|
0.00%
0/3
|
3.3%
1/30
|
0.00%
0/3
|
|
Nervous system disorders
Cerebral infarction
|
0.00%
0/3
|
3.3%
1/30
|
0.00%
0/3
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/3
|
3.3%
1/30
|
0.00%
0/3
|
|
Blood and lymphatic system disorders
Disseminated intravascular coagulation
|
0.00%
0/3
|
0.00%
0/30
|
33.3%
1/3
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/3
|
3.3%
1/30
|
0.00%
0/3
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.00%
0/3
|
3.3%
1/30
|
0.00%
0/3
|
|
Gastrointestinal disorders
Gastric ulcer haemorrhage
|
0.00%
0/3
|
3.3%
1/30
|
0.00%
0/3
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/3
|
3.3%
1/30
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/3
|
3.3%
1/30
|
33.3%
1/3
|
|
Metabolism and nutrition disorders
Hypoproteinaemia
|
0.00%
0/3
|
3.3%
1/30
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/3
|
3.3%
1/30
|
0.00%
0/3
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/3
|
3.3%
1/30
|
0.00%
0/3
|
|
Renal and urinary disorders
Nephrotic syndrome
|
0.00%
0/3
|
3.3%
1/30
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
0.00%
0/3
|
3.3%
1/30
|
0.00%
0/3
|
|
Investigations
Platelet count decreased
|
0.00%
0/3
|
6.7%
2/30
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
0.00%
0/3
|
3.3%
1/30
|
0.00%
0/3
|
|
Infections and infestations
Pyelonephritis acute
|
0.00%
0/3
|
3.3%
1/30
|
0.00%
0/3
|
|
Gastrointestinal disorders
Reflux oesophagitis
|
0.00%
0/3
|
3.3%
1/30
|
0.00%
0/3
|
|
Infections and infestations
Sepsis
|
0.00%
0/3
|
0.00%
0/30
|
33.3%
1/3
|
|
Gastrointestinal disorders
Subileus
|
0.00%
0/3
|
3.3%
1/30
|
33.3%
1/3
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour haemorrhage
|
0.00%
0/3
|
3.3%
1/30
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract inflammation
|
0.00%
0/3
|
3.3%
1/30
|
0.00%
0/3
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/3
|
3.3%
1/30
|
0.00%
0/3
|
Other adverse events
| Measure |
SU-011248 25-mg
n=3 participants at risk
Subjects received sunitinib malate (SU-011248) at starting dose of 25-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be increased to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
SU-011248 50-mg
n=30 participants at risk
Subjects received sunitinib malate (SU-011248) at starting dose of 50-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
From Phase 1 part of this study, 50-mg was determined as the maximum tolerated dose and the recommended dose.
|
SU-011248 75-mg
n=3 participants at risk
Subjects received sunitinib malate (SU-011248) at starting dose of 75-mg once daily. Treatment cycles were 6 weeks in duration, consisting of 4 weeks daily SU-011248 administration followed by 2 weeks off treatment.
Phase 1: If Dose Limiting Toxicity (DLT) was observed, the patients were withdrawn from the study treatment. Neither temporary discontinuation nor reduction was permitted.
Phase 2: The initial dose could be reduced to the recommended dose. Treatment cycles were repeated until a study treatment withdrawal criterion was met. If drug-related adverse event (grade\>=3) was observed, temporary discontinuation or dose reduction were taken according to the criteria.
|
|---|---|---|---|
|
Investigations
Blood bilirubin increased
|
33.3%
1/3
|
30.0%
9/30
|
66.7%
2/3
|
|
Investigations
Blood calcium decreased
|
0.00%
0/3
|
13.3%
4/30
|
33.3%
1/3
|
|
Gastrointestinal disorders
Abdominal distension
|
33.3%
1/3
|
13.3%
4/30
|
33.3%
1/3
|
|
Gastrointestinal disorders
Abdominal pain
|
66.7%
2/3
|
56.7%
17/30
|
33.3%
1/3
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/3
|
13.3%
4/30
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Acne
|
0.00%
0/3
|
0.00%
0/30
|
33.3%
1/3
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/3
|
46.7%
14/30
|
33.3%
1/3
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/3
|
16.7%
5/30
|
0.00%
0/3
|
|
Infections and infestations
Anal abscess
|
0.00%
0/3
|
0.00%
0/30
|
33.3%
1/3
|
|
Gastrointestinal disorders
Anal haemorrhage
|
33.3%
1/3
|
0.00%
0/30
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Anorexia
|
33.3%
1/3
|
73.3%
22/30
|
100.0%
3/3
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/3
|
6.7%
2/30
|
0.00%
0/3
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/3
|
10.0%
3/30
|
0.00%
0/3
|
|
Investigations
Aspartate aminotransferase increased
|
33.3%
1/3
|
60.0%
18/30
|
66.7%
2/3
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/3
|
16.7%
5/30
|
33.3%
1/3
|
|
Investigations
Blood albumin decreased
|
0.00%
0/3
|
56.7%
17/30
|
66.7%
2/3
|
|
Investigations
Blood alkaline phosphatase increased
|
33.3%
1/3
|
36.7%
11/30
|
100.0%
3/3
|
|
Investigations
Blood amylase increased
|
0.00%
0/3
|
26.7%
8/30
|
100.0%
3/3
|
|
Investigations
Blood creatinine increased
|
33.3%
1/3
|
33.3%
10/30
|
33.3%
1/3
|
|
Investigations
Blood glucose increased
|
0.00%
0/3
|
6.7%
2/30
|
0.00%
0/3
|
|
Investigations
Blood lactate dehydrogenase increased
|
0.00%
0/3
|
40.0%
12/30
|
66.7%
2/3
|
|
Investigations
Blood phosphorus decreased
|
0.00%
0/3
|
10.0%
3/30
|
0.00%
0/3
|
|
Investigations
Blood potassium decreased
|
0.00%
0/3
|
0.00%
0/30
|
33.3%
1/3
|
|
Investigations
Blood potassium increased
|
0.00%
0/3
|
3.3%
1/30
|
66.7%
2/3
|
|
Investigations
Blood urea increased
|
0.00%
0/3
|
3.3%
1/30
|
33.3%
1/3
|
|
Investigations
Blood uric acid increased
|
0.00%
0/3
|
10.0%
3/30
|
0.00%
0/3
|
|
Investigations
C-reactive protein increased
|
0.00%
0/3
|
13.3%
4/30
|
33.3%
1/3
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
|
33.3%
1/3
|
0.00%
0/30
|
0.00%
0/3
|
|
General disorders
Catheter site related reaction
|
0.00%
0/3
|
0.00%
0/30
|
33.3%
1/3
|
|
Gastrointestinal disorders
Cheilitis
|
33.3%
1/3
|
30.0%
9/30
|
33.3%
1/3
|
|
General disorders
Chest pain
|
33.3%
1/3
|
6.7%
2/30
|
0.00%
0/3
|
|
General disorders
Chills
|
0.00%
0/3
|
0.00%
0/30
|
33.3%
1/3
|
|
Eye disorders
Conjunctivitis
|
0.00%
0/3
|
10.0%
3/30
|
0.00%
0/3
|
|
Gastrointestinal disorders
Constipation
|
33.3%
1/3
|
26.7%
8/30
|
33.3%
1/3
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/3
|
16.7%
5/30
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Dehydration
|
33.3%
1/3
|
20.0%
6/30
|
0.00%
0/3
|
|
Gastrointestinal disorders
Diarrhoea
|
100.0%
3/3
|
76.7%
23/30
|
100.0%
3/3
|
|
Nervous system disorders
Dizziness
|
33.3%
1/3
|
0.00%
0/30
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
33.3%
1/3
|
6.7%
2/30
|
0.00%
0/3
|
|
Nervous system disorders
Dysgeusia
|
33.3%
1/3
|
43.3%
13/30
|
66.7%
2/3
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/3
|
10.0%
3/30
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
0.00%
0/3
|
10.0%
3/30
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/3
|
6.7%
2/30
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Eczema
|
33.3%
1/3
|
0.00%
0/30
|
0.00%
0/3
|
|
Investigations
Ejection fraction decreased
|
0.00%
0/3
|
20.0%
6/30
|
0.00%
0/3
|
|
Gastrointestinal disorders
Epigastric discomfort
|
0.00%
0/3
|
0.00%
0/30
|
33.3%
1/3
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
66.7%
2/3
|
13.3%
4/30
|
0.00%
0/3
|
|
Eye disorders
Eyelid oedema
|
33.3%
1/3
|
3.3%
1/30
|
0.00%
0/3
|
|
General disorders
Face oedema
|
0.00%
0/3
|
6.7%
2/30
|
0.00%
0/3
|
|
General disorders
Fatigue
|
66.7%
2/3
|
76.7%
23/30
|
66.7%
2/3
|
|
Gastrointestinal disorders
Flatulence
|
33.3%
1/3
|
0.00%
0/30
|
0.00%
0/3
|
|
Infections and infestations
Folliculitis
|
0.00%
0/3
|
0.00%
0/30
|
33.3%
1/3
|
|
Investigations
Gamma-glutamyltransferase increased
|
0.00%
0/3
|
10.0%
3/30
|
0.00%
0/3
|
|
Reproductive system and breast disorders
Genital haemorrhage
|
33.3%
1/3
|
0.00%
0/30
|
0.00%
0/3
|
|
Gastrointestinal disorders
Gingivitis
|
33.3%
1/3
|
43.3%
13/30
|
0.00%
0/3
|
|
Gastrointestinal disorders
Glossitis
|
0.00%
0/3
|
6.7%
2/30
|
0.00%
0/3
|
|
Musculoskeletal and connective tissue disorders
Gouty arthritis
|
0.00%
0/3
|
0.00%
0/30
|
33.3%
1/3
|
|
Vascular disorders
Haematoma
|
0.00%
0/3
|
0.00%
0/30
|
33.3%
1/3
|
|
Investigations
Haemoglobin decreased
|
66.7%
2/3
|
73.3%
22/30
|
100.0%
3/3
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/3
|
6.7%
2/30
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Haemorrhage subcutaneous
|
0.00%
0/3
|
13.3%
4/30
|
0.00%
0/3
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.00%
0/3
|
6.7%
2/30
|
100.0%
3/3
|
|
Nervous system disorders
Headache
|
33.3%
1/3
|
26.7%
8/30
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/3
|
3.3%
1/30
|
33.3%
1/3
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/3
|
13.3%
4/30
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Hypernatraemia
|
0.00%
0/3
|
6.7%
2/30
|
0.00%
0/3
|
|
Vascular disorders
Hypertension
|
0.00%
0/3
|
50.0%
15/30
|
66.7%
2/3
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
33.3%
1/3
|
6.7%
2/30
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
0.00%
0/3
|
3.3%
1/30
|
33.3%
1/3
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.00%
0/3
|
10.0%
3/30
|
33.3%
1/3
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
33.3%
1/3
|
6.7%
2/30
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/3
|
6.7%
2/30
|
0.00%
0/3
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
0.00%
0/3
|
3.3%
1/30
|
66.7%
2/3
|
|
Metabolism and nutrition disorders
Hypoproteinaemia
|
0.00%
0/3
|
6.7%
2/30
|
0.00%
0/3
|
|
Endocrine disorders
Hypothyroidism
|
33.3%
1/3
|
16.7%
5/30
|
0.00%
0/3
|
|
Infections and infestations
Infection
|
0.00%
0/3
|
0.00%
0/30
|
33.3%
1/3
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/3
|
10.0%
3/30
|
33.3%
1/3
|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
33.3%
1/3
|
0.00%
0/30
|
0.00%
0/3
|
|
Hepatobiliary disorders
Jaundice
|
0.00%
0/3
|
0.00%
0/30
|
33.3%
1/3
|
|
Cardiac disorders
Left ventricular dysfunction
|
0.00%
0/3
|
6.7%
2/30
|
0.00%
0/3
|
|
Investigations
Leucine aminopeptidase increased
|
0.00%
0/3
|
6.7%
2/30
|
0.00%
0/3
|
|
Investigations
Lipase increased
|
0.00%
0/3
|
36.7%
11/30
|
66.7%
2/3
|
|
Investigations
Lymphocyte count decreased
|
66.7%
2/3
|
56.7%
17/30
|
66.7%
2/3
|
|
General disorders
Malaise
|
33.3%
1/3
|
3.3%
1/30
|
0.00%
0/3
|
|
Investigations
Monocyte count decreased
|
0.00%
0/3
|
0.00%
0/30
|
33.3%
1/3
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/3
|
6.7%
2/30
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Nail discolouration
|
33.3%
1/3
|
0.00%
0/30
|
0.00%
0/3
|
|
Respiratory, thoracic and mediastinal disorders
Nasal mucosal disorder
|
0.00%
0/3
|
10.0%
3/30
|
0.00%
0/3
|
|
Infections and infestations
Nasopharyngitis
|
66.7%
2/3
|
33.3%
10/30
|
33.3%
1/3
|
|
Gastrointestinal disorders
Nausea
|
66.7%
2/3
|
50.0%
15/30
|
100.0%
3/3
|
|
Renal and urinary disorders
Nephrotic syndrome
|
0.00%
0/3
|
6.7%
2/30
|
0.00%
0/3
|
|
Nervous system disorders
Neuropathy peripheral
|
33.3%
1/3
|
3.3%
1/30
|
0.00%
0/3
|
|
Investigations
Neutrophil count decreased
|
100.0%
3/3
|
93.3%
28/30
|
100.0%
3/3
|
|
General disorders
Oedema
|
0.00%
0/3
|
30.0%
9/30
|
33.3%
1/3
|
|
General disorders
Oedema peripheral
|
0.00%
0/3
|
23.3%
7/30
|
0.00%
0/3
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
33.3%
1/3
|
0.00%
0/30
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
66.7%
2/3
|
86.7%
26/30
|
100.0%
3/3
|
|
Cardiac disorders
Pericardial effusion
|
0.00%
0/3
|
6.7%
2/30
|
0.00%
0/3
|
|
Gastrointestinal disorders
Periodontitis
|
0.00%
0/3
|
10.0%
3/30
|
0.00%
0/3
|
|
Gastrointestinal disorders
Periproctitis
|
0.00%
0/3
|
0.00%
0/30
|
33.3%
1/3
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/3
|
30.0%
9/30
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Pigmentation disorder
|
0.00%
0/3
|
23.3%
7/30
|
66.7%
2/3
|
|
Investigations
Platelet count decreased
|
66.7%
2/3
|
86.7%
26/30
|
100.0%
3/3
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/3
|
6.7%
2/30
|
33.3%
1/3
|
|
Investigations
Protein total decreased
|
0.00%
0/3
|
26.7%
8/30
|
66.7%
2/3
|
|
Investigations
Protein urine
|
0.00%
0/3
|
13.3%
4/30
|
0.00%
0/3
|
|
Investigations
Protein urine present
|
33.3%
1/3
|
3.3%
1/30
|
0.00%
0/3
|
|
Renal and urinary disorders
Proteinuria
|
33.3%
1/3
|
6.7%
2/30
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
33.3%
1/3
|
10.0%
3/30
|
33.3%
1/3
|
|
Skin and subcutaneous tissue disorders
Purpura
|
0.00%
0/3
|
6.7%
2/30
|
33.3%
1/3
|
|
General disorders
Pyrexia
|
0.00%
0/3
|
33.3%
10/30
|
100.0%
3/3
|
|
Skin and subcutaneous tissue disorders
Rash
|
33.3%
1/3
|
46.7%
14/30
|
66.7%
2/3
|
|
Investigations
Red blood cell count decreased
|
0.00%
0/3
|
13.3%
4/30
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Skin discolouration
|
0.00%
0/3
|
70.0%
21/30
|
66.7%
2/3
|
|
Injury, poisoning and procedural complications
Spinal compression fracture
|
0.00%
0/3
|
0.00%
0/30
|
33.3%
1/3
|
|
Gastrointestinal disorders
Stomatitis
|
66.7%
2/3
|
63.3%
19/30
|
66.7%
2/3
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/3
|
6.7%
2/30
|
0.00%
0/3
|
|
Gastrointestinal disorders
Vomiting
|
66.7%
2/3
|
33.3%
10/30
|
33.3%
1/3
|
|
Investigations
Weight decreased
|
0.00%
0/3
|
6.7%
2/30
|
0.00%
0/3
|
|
Investigations
Weight increased
|
0.00%
0/3
|
13.3%
4/30
|
0.00%
0/3
|
|
Investigations
White blood cell count decreased
|
100.0%
3/3
|
90.0%
27/30
|
100.0%
3/3
|
|
Investigations
White blood cell count increased
|
0.00%
0/3
|
0.00%
0/30
|
33.3%
1/3
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of \< 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), \< 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential info other than study results.
- Publication restrictions are in place
Restriction type: OTHER