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CompletedNCT00457743Updated Nov 13, 2009Results posted

A Phase I/II Study of Sunitinib Malate (SU011248) In Patients With Gastrointestinal Stromal Tumor (GIST)

A Phase 1/2 interventional study of Sunitinib malate (SU011248) in Gastrointestinal Stromal Tumors, sponsored by Pfizer. Completed at 4 sites in Japan. Open to participants aged 20 Years to 75 Years. Per ClinicalTrials.gov, last updated 2009-11-13.

Sponsored by Pfizer · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
36
Allocation
Non-randomized
Ages
20 Years to 75 Years
Sex
All
01

Study summary

Phase I;To investigate the clinically recommended dose of Sunitinib malate (SU011248) following multiple oral dosing in the first cycle (4 consecutive weeks and 2 weeks rest) by reviewing the safety and tolerability.

Phase II;To determine the objective tumor response and the safety of Sunitinib malate (SU011248) at the clinically recommended dose.

02

Conditions studied

  • Gastrointestinal Stromal Tumors

Keywords

  • Evaluate of RTD for Japanese GIST patients
03

In context

Gastrointestinal Stromal Tumors

333 studies on the registry are indexed under Gastrointestinal Stromal Tumors; 61 are open to participants now.

This study's enrollment of 36 is below the median of 50 across 243 interventional studies indexed under Gastrointestinal Stromal Tumors.

Browse Gastrointestinal Stromal Tumors studies →

Lead sponsor

Pfizer is the lead sponsor of 3,244 studies on the registry; 139 are open to participants now.

Of its 582 completed or terminated interventional studies of FDA-regulated products, 381 (65%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
20 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Patients with histologically-confirmed metastatic or unresectable gastrointestinal stromal tumor (GIST).
  • Patients previously treated with imatinib mesylate.

Exclusion criteria

Exclusion Criteria:

  • Patients who have not recovered from the acute toxic effects of previous antineoplastic therapy or treatment with imatinib mesylate.
  • Any tumor therapy for gastrointestinal stromal tumor (GIST) discontinued less than 4 weeks prior to starting study treatment. Imatinib mesylate discontinued less than 2 weeks prior to starting therapy.
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
36 participants (actual)

Study arms

  • Experimental
    SU011248

    25 , 50 or 75 mg/day of SU011248

    Drug: Sunitinib malate (SU011248)

Interventions

  • DrugSunitinib malate (SU011248)

    SU011248

06

What researchers measure

Primary outcomes

  1. Number of Subjects With Dose Limiting Toxicities (DLT)

    Dose Limiting Toxicities(DLT) in the subjects enrolled in Phase 1.

    Time frame: Cycle 1 (Baseline to Week 6)

  2. Maximum Plasma Concentration (Cmax) on Cycle 1 Day 1

    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).

    Time frame: Day 1 of Cycle 1

  3. Maximum Plasma Concentration (Cmax) on Cycle 1 Day 28

    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).

    Time frame: Day 28 of Cycle 1

  4. Area Under the Plasma Concentration Curve (AUC0-24) on Cycle 1 Day 1

    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).

    Time frame: Day 1 of Cycle 1

  5. Area Under the Plasma Concentration Curve (AUC0-24) on Cycle 1 Day 28

    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).

    Time frame: Day 28 of Cycle 1

  6. Time to First Occurrence of Cmax (Tmax) on Cycle 1 Day 1

    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).

    Time frame: Day 1 of Cycle 1

  7. Time to First Occurrence of Cmax (Tmax) on Cycle 1 Day 28

    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).

    Time frame: Day 28 of Cycle 1

  8. SU-011248 Clearance on Cycle 1 Day 28

    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).

    Time frame: Day 28 of Cycle 1

  9. Accumulation Ratio (Rac) on Cycle 1 Day 28

    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.

    Time frame: Day 28 of Cycle 1

  10. Number of Subjects With Clinical Benefit Response (CBR) Based on the Extramural Review Committee Assessment in Recommended Dose Group

    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).

    Time frame: Day 28 of Cycles 1-4

Secondary outcomes

  1. Plasma Concentrations of Vascular Endothelial Growth Factor (VEGF)

    Plasma concentrations of potential pharmacodynamic markers; Vascular Endothelial Growth Factor (VEGF)

    Time frame: Day 1, 14, 28 of Cycles 1-4

  2. Plasma Concentrations of Soluble Vascular Endothelial Growth Factor Type 2 Receptors (sVEGFR2)

    Plasma concentrations of potential pharmacodynamic markers; Soluble Vascular Endothelial Growth Factor Type 2 Receptors (sVEGFR2)

    Time frame: Day 1, 14, 28 of Cycles 1-4

  3. Plasma Concentrations of Soluble Stem Cell Factor Receptor (sKIT)

    Plasma concentrations of potential pharmacodynamic markers; Soluble Stem Cell Factor Receptor (sKIT)

    Time frame: Day 1, 14, 28 of Cycles 1-4

  4. Trough Plasma Concentration (Ctrough) of SU-011248

    Trough Plasma Concentration (Ctrough) means the concentration prior to study drug administration

    Time frame: Day 14, 28 of Cycle 1; Day 1, 14, 28 of Cycles 2-4

  5. Trough Plasma Concentration (Ctrough) of SU-012262

    Trough Plasma Concentration (Ctrough) means the concentration prior to study drug administration

    Time frame: Day 14, 28 of Cycle 1; Day 1, 14, 28 of Cycles 2-4

  6. Trough Plasma Concentration (Ctrough) of SU-011248+SU-012662

    Trough Plasma Concentration (Ctrough) means the concentration prior to study drug administration

    Time frame: Day 14, 28 of Cycle 1; Day 1, 14, 28 of Cycles 2-4

  7. Changes From Baseline of Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaires

    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

    Time frame: Day 7, 14, 28, 35 of Cycle 1; Day 1, 7, 14, 28, 35 of Cycles 2-4

  8. Change From Baseline of European Quality of Life Questionnaire- 5 Dimensions(EQ-5D) Questionnaires

    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

    Time frame: Day 28 of Cycle 1; Day 1, 28 of Cycles 2-4

  9. Number of Subjects With Disease Controlled Based on the Extramural Review Committee Assessment in Recommended Dose Group

    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).

    Time frame: Day 28 of Cycles 1-4

  10. Number of Subjects With Objective Response Based on the Extramural Review Committee Assessment in Recommended Dose Group

    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).

    Time frame: Day 28 of Cycles 1-4

  11. Time To Tumor Progression (TTP)

    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).

    Time frame: From the first dose to Progressive Disease

  12. Progression-Free Survival (PFS)

    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.

    Time frame: From the first dose to Progressive Disease or Death

  13. Time To Failure (TTF)

    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.

    Time frame: From the first dose to Progressive Disease, Treatment discontinuation except completion of treatment, or Death due to cancer.

  14. Overall Survival Time

    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.

    Time frame: From the first dose to death

07

Results

Posted Nov 13, 2009

Participant flow

Participant flow — Overall Study
MilestoneSU-011248 25-mgSU-011248 50-mgSU-011248 75-mg
Started3303
Enrolled in phase 1363
Completed phase 1363
Enrolled in phase 23303
Completed030
Not completed3273
Withdrew: Adverse event040
Withdrew: Lack of efficacy3233

Outcome measures

PrimaryNumber of Subjects With Dose Limiting Toxicities (DLT)

Dose Limiting Toxicities(DLT) in the subjects enrolled in Phase 1.

Time frame:
Cycle 1 (Baseline to Week 6)
Reported as:
Number · participants
Number of Subjects With Dose Limiting Toxicities (DLT)
participantsSU-011248 25-mgSU-011248 50-mgSU-011248 75-mg
Number of Subjects With Dose Limiting Toxicities (DLT)002
PrimaryMaximum Plasma Concentration (Cmax) on Cycle 1 Day 1

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).

Time frame:
Day 1 of Cycle 1
Reported as:
Mean · ng/mL
Maximum Plasma Concentration (Cmax) on Cycle 1 Day 1
ng/mLSU-011248 25-mgSU-011248 50-mgSU-011248 75-mg
SU-01124812.1 ± 4.922.8 ± 6.432.3 ± 20.8
SU-0126621.96 ± 1.274.13 ± 0.934.81 ± 2.54
SU-011248+SU-01266214.1 ± 6.126.7 ± 7.437.0 ± 22.1
SecondaryPlasma Concentrations of Vascular Endothelial Growth Factor (VEGF)

Plasma concentrations of potential pharmacodynamic markers; Vascular Endothelial Growth Factor (VEGF)

Time frame:
Day 1, 14, 28 of Cycles 1-4
Reported as:
Mean · pg/mL
Plasma Concentrations of Vascular Endothelial Growth Factor (VEGF)
pg/mLSU-011248 50-mg
Cycle 1 Day 1 (n=30)55.30 ± 32.43
Cycle 1 Day 14 (n=30)179.94 ± 116.00
Cycle 1 Day 28 (n=19)192.42 ± 210.58
Cycle 2 Day 1 (n=26)62.05 ± 38.20
Cycle 2 Day 14 (n=24)173.12 ± 96.30
Cycle 2 Day 28 (n=20)207.79 ± 158.05
Cycle 3 Day 1 (n=18)58.80 ± 26.13
Cycle 3 Day 14 (n=19)208.93 ± 159.41
Cycle 3 Day 28 (n=13)238.74 ± 227.63
Cycle 4 Day 1 (n=11)54.83 ± 14.86
Cycle 4 Day 14 (n=12)227.28 ± 163.52
Cycle 4 Day 28 (n=9)343.21 ± 210.28
SecondaryPlasma Concentrations of Soluble Vascular Endothelial Growth Factor Type 2 Receptors (sVEGFR2)

Plasma concentrations of potential pharmacodynamic markers; Soluble Vascular Endothelial Growth Factor Type 2 Receptors (sVEGFR2)

Time frame:
Day 1, 14, 28 of Cycles 1-4
Reported as:
Mean · pg/mL
Plasma Concentrations of Soluble Vascular Endothelial Growth Factor Type 2 Receptors (sVEGFR2)
pg/mLSU-011248 50-mg
Cycle 1 Day 1 (n=30)8740.20 ± 1702.84
Cycle 1 Day 14 (n=30)5721.98 ± 1136.89
Cycle 1 Day 28 (n=19)5082.92 ± 1449.26
Cycle 2 Day 1 (n=26)7579.98 ± 1844.58
Cycle 2 Day 14 (n=24)5808.08 ± 1484.30
Cycle 2 Day 28 (n=20)4770.15 ± 1311.88
Cycle 3 Day 1 (n=18)6802.86 ± 1641.46
Cycle 3 Day 14 (n=19)5022.84 ± 1192.52
Cycle 3 Day 28 (n=13)4297.91 ± 1157.62
Cycle 4 Day 1 (n=11)6559.50 ± 1152.24
Cycle 4 Day 14 (n=12)5038.50 ± 1078.45
Cycle 4 Day 28 (n=9)4142.72 ± 1103.29
SecondaryPlasma Concentrations of Soluble Stem Cell Factor Receptor (sKIT)

Plasma concentrations of potential pharmacodynamic markers; Soluble Stem Cell Factor Receptor (sKIT)

Time frame:
Day 1, 14, 28 of Cycles 1-4
Reported as:
Mean · pg/mL
Plasma Concentrations of Soluble Stem Cell Factor Receptor (sKIT)
pg/mLSU-011248 50-mg
Cycle 1 Day 1 (n=30)48237.33 ± 56643.93
Cycle 1 Day 14 (n=30)53087.75 ± 71243.85
Cycle 1 Day 28 (n=19)35538.95 ± 16082.33
Cycle 2 Day 1 (n=26)39011.35 ± 38304.60
Cycle 2 Day 14 (n=24)40432.29 ± 45085.57
Cycle 2 Day 28 (n=20)30715.75 ± 16212.04
Cycle 3 Day 1 (n=18)27814.17 ± 10362.85
Cycle 3 Day 14 (n=19)32973.68 ± 14483.42
Cycle 3 Day 28 (n=13)32760.77 ± 16888.75
Cycle 4 Day 1 (n=11)28961.82 ± 14899.42
Cycle 4 Day 14 (n=12)32265.83 ± 16143.54
Cycle 4 Day 28 (n=9)32571.11 ± 20949.63
SecondaryTrough Plasma Concentration (Ctrough) of SU-011248

Trough Plasma Concentration (Ctrough) means the concentration prior to study drug administration

Time frame:
Day 14, 28 of Cycle 1; Day 1, 14, 28 of Cycles 2-4
Reported as:
Mean · ng/mL
Trough Plasma Concentration (Ctrough) of SU-011248
ng/mLSU-011248 50-mg
Cycle 1 Day 14 (n=28)58.93 ± 23.87
Cycle 1 Day 28 (n=18)44.52 ± 15.45
Cycle 2 Day 1 (n=15)1.17 ± 0.60
Cycle 2 Day 14 (n=23)51.23 ± 16.98
Cycle 2 Day 28 (n=20)48.09 ± 22.41
Cycle 3 Day 1 (n=11)1.62 ± 0.88
Cycle 3 Day 14 (n=14)58.72 ± 27.09
Cycle 3 Day 28 (n=10)47.13 ± 21.73
Cycle 4 Day 1 (n=5)1.52 ± 0.81
Cycle 4 Day 14 (n=7)46.13 ± 22.28
Cycle 4 Day 28 (n=8)47.33 ± 12.95
SecondaryTrough Plasma Concentration (Ctrough) of SU-012262

Trough Plasma Concentration (Ctrough) means the concentration prior to study drug administration

Time frame:
Day 14, 28 of Cycle 1; Day 1, 14, 28 of Cycles 2-4
Reported as:
Mean · ng/mL
Trough Plasma Concentration (Ctrough) of SU-012262
ng/mLSU-011248 50-mg
Cycle 1 Day 14 (n=28)26.41 ± 15.86
Cycle 1 Day 28 (n=18)24.52 ± 13.28
Cycle 2 Day 1 (n=15)2.01 ± 0.90
Cycle 2 Day 14 (n=23)24.06 ± 11.54
Cycle 2 Day 28 (n=20)24.47 ± 14.92
Cycle 3 Day 1 (n=11)2.26 ± 1.20
Cycle 3 Day 14 (n=14)27.69 ± 16.34
Cycle 3 Day 28 (n=10)23.83 ± 12.59
Cycle 4 Day 1 (n=5)2.02 ± 0.90
Cycle 4 Day 14 (n=7)19.86 ± 11.38
Cycle 4 Day 28 (n=8)25.94 ± 12.28
SecondaryTrough Plasma Concentration (Ctrough) of SU-011248+SU-012662

Trough Plasma Concentration (Ctrough) means the concentration prior to study drug administration

Time frame:
Day 14, 28 of Cycle 1; Day 1, 14, 28 of Cycles 2-4
Reported as:
Mean · ng/mL
Trough Plasma Concentration (Ctrough) of SU-011248+SU-012662
ng/mLSU-011248 50-mg
Cycle 1 Day 14 (n=28)85.33 ± 36.59
Cycle 1 Day 28 (n=18)69.05 ± 27.52
Cycle 2 Day 1 (n=15)3.18 ± 1.45
Cycle 2 Day 14 (n=23)75.29 ± 27.35
Cycle 2 Day 28 (n=20)72.56 ± 36.14
Cycle 3 Day 1 (n=11)3.88 ± 1.88
Cycle 3 Day 14 (n=14)86.41 ± 42.83
Cycle 3 Day 28 (n=10)70.96 ± 32.81
Cycle 4 Day 1 (n=5)3.54 ± 1.46
Cycle 4 Day 14 (n=7)65.99 ± 33.42
Cycle 4 Day 28 (n=8)73.26 ± 24.82
SecondaryChanges From Baseline of Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaires

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

Time frame:
Day 7, 14, 28, 35 of Cycle 1; Day 1, 7, 14, 28, 35 of Cycles 2-4
Reported as:
Mean · scores on a scale
Changes From Baseline of Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaires
scores on a scaleSU-011248 50-mg
Cycle 1 Day 7 (n=30)1.0 ± 5.6
Cycle 1 Day 14 (n=30)-2.3 ± 7.8
Cycle 1 Day 21 (n=30)-6.3 ± 13.8
Cycle 1 Day 28 (n=30)-4.6 ± 10.2
Cycle 1 Day 35 (n=30)-0.4 ± 6.6
Cycle 2 Day 1 (n=30)1.5 ± 5.8
Cycle 2 Day 7 (n=30)-0.2 ± 8.0
Cycle 2 Day 14 (n=30)-1.3 ± 8.7
Cycle 2 Day 21 (n=30)-3.6 ± 10.5
Cycle 2 Day 28 (n=29)-5.1 ± 10.6
Cycle 2 Day 35 (n=29)-2.5 ± 8.7
Cycle 3 Day 1 (n=25)-1.3 ± 8.6
Cycle 3 Day 7 (n=24)-1.2 ± 6.6
Cycle 3 Day 14 (n=25)-1.8 ± 9.3
Cycle 3 Day 21 (n=24)-4.8 ± 9.8
Cycle 3 Day 28 (n=25)-3.8 ± 10.0
Cycle 3 Day 35 (n=25)-3.4 ± 10.4
Cycle 4 Day 1 (n=21)-2.7 ± 9.5
Cycle 4 Day 7 (n=20)-4.4 ± 11.4
Cycle 4 Day 14 (n=21)-6.2 ± 11.5
Cycle 4 Day 21 (n=20)-8.8 ± 12.5
Cycle 4 Day 28 (n=19)-9.7 ± 11.5
Cycle 4 Day 35 (n=20)-8.6 ± 11.2
SecondaryChange From Baseline of European Quality of Life Questionnaire- 5 Dimensions(EQ-5D) Questionnaires

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

Time frame:
Day 28 of Cycle 1; Day 1, 28 of Cycles 2-4
Reported as:
Mean · index scores on a scale
Change From Baseline of European Quality of Life Questionnaire- 5 Dimensions(EQ-5D) Questionnaires
index scores on a scaleSU-011248 50-mg
Cycle 1 Day 28 (n=30)-0.148 ± 0.213
Cycle 2 Day 1 (n=30)-0.038 ± 0.171
Cycle 2 Day 28 (n=30)-0.121 ± 0.215
Cycle 3 Day 1 (n=25)-0.010 ± 0.125
Cycle 3 Day 28 (n=25)-0.091 ± 0.210
Cycle 4 Day 1 (n=21)-0.006 ± 0.137
Cycle 4 Day 28 (n=18)-0.142 ± 0.198
SecondaryNumber of Subjects With Disease Controlled Based on the Extramural Review Committee Assessment in Recommended Dose Group

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).

Time frame:
Day 28 of Cycles 1-4
Reported as:
Number · participants
Number of Subjects With Disease Controlled Based on the Extramural Review Committee Assessment in Recommended Dose Group
participantsSU-011248 50-mg
Total number of Subjects with CR+PR+SD>=10weeks17
Complete Response (CR)0
Partial Response (PR)4
Stable Disease (SD) >= 10 weeks13
Statistical analysis
  • SU-011248 50-mg · Disease control rate (percentage): 56.7 · 95% CI 37.4 to 74.5The disease control rate, defined as the percentage of subjects confirmed with CR, PR, and SD \>=10 weeks on study according to RECIST.
PrimaryMaximum Plasma Concentration (Cmax) on Cycle 1 Day 28

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).

Time frame:
Day 28 of Cycle 1
Reported as:
Mean · ng/mL
Maximum Plasma Concentration (Cmax) on Cycle 1 Day 28
ng/mLSU-011248 25-mgSU-011248 50-mg
SU-01124839.5 ± 25.069.3 ± 18.9
SU-01266215.2 ± 10.238.8 ± 16.0
SU-011248+SU-01266254.0 ± 32.2105 ± 35
SecondaryNumber of Subjects With Objective Response Based on the Extramural Review Committee Assessment in Recommended Dose Group

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).

Time frame:
Day 28 of Cycles 1-4
Reported as:
Number · participants
Number of Subjects With Objective Response Based on the Extramural Review Committee Assessment in Recommended Dose Group
participantsSU-011248 50-mg
Total Number of Subjects with CR+PR4
Complete Response (CR)0
Partial Response (PR)4
Statistical analysis
  • SU-011248 50-mg · Objective response rate(percentage): 13.3 · 95% CI 3.8 to 30.7The subjects confirmed with complete response (CR) and partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST).
SecondaryTime To Tumor Progression (TTP)

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).

Time frame:
From the first dose to Progressive Disease
Reported as:
Median · Weeks
Time To Tumor Progression (TTP)
WeeksSU-011248 50-mg
Time To Tumor Progression (TTP)30.3 (22.0 to 46.1)
PrimaryArea Under the Plasma Concentration Curve (AUC0-24) on Cycle 1 Day 1

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).

Time frame:
Day 1 of Cycle 1
Reported as:
Mean · ng•h/mL
Area Under the Plasma Concentration Curve (AUC0-24) on Cycle 1 Day 1
ng•h/mLSU-011248 25-mgSU-011248 50-mgSU-011248 75-mg
SU-011248199 ± 89374 ± 69508 ± 259
SU-01266230.9 ± 20.670.0 ± 14.491.1 ± 45.3
SU-011248+SU-012662230 ± 108444 ± 82599 ± 287
PrimaryArea Under the Plasma Concentration Curve (AUC0-24) on Cycle 1 Day 28

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).

Time frame:
Day 28 of Cycle 1
Reported as:
Mean · ng•h/mL
Area Under the Plasma Concentration Curve (AUC0-24) on Cycle 1 Day 28
ng•h/mLSU-011248 25-mgSU-011248 50-mg
SU-011248858 ± 6001406 ± 364
SU-012662324 ± 223772 ± 358
SU-011248+SU-0126621182 ± 7342178 ± 702
PrimaryTime to First Occurrence of Cmax (Tmax) on Cycle 1 Day 1

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).

Time frame:
Day 1 of Cycle 1
Reported as:
Median · hours
Time to First Occurrence of Cmax (Tmax) on Cycle 1 Day 1
hoursSU-011248 25-mgSU-011248 50-mgSU-011248 75-mg
SU-0112486 (4 to 8)7 (6 to 24)8 (4 to 10)
SU-0126626 (4 to 8)9 (6 to 24)10 (4 to 10)
SU-011248+SU-0126626 (4 to 8)7 (6 to 24)8 (4 to 10)
PrimaryTime to First Occurrence of Cmax (Tmax) on Cycle 1 Day 28

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).

Time frame:
Day 28 of Cycle 1
Reported as:
Median · hours
Time to First Occurrence of Cmax (Tmax) on Cycle 1 Day 28
hoursSU-011248 25-mgSU-011248 50-mg
SU-01124810 (6 to 10)6 (1 to 24)
SU-0126624 (2 to 8)2.5 (0 to 48)
SU-011248+SU-0126626 (4 to 8)6 (0 to 24)
SecondaryProgression-Free Survival (PFS)

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.

Time frame:
From the first dose to Progressive Disease or Death
Reported as:
Median · Weeks
Progression-Free Survival (PFS)
WeeksSU-011248 50-mg
Progression-Free Survival (PFS)30.3 (22.0 to 46.1)
PrimarySU-011248 Clearance on Cycle 1 Day 28

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).

Time frame:
Day 28 of Cycle 1
Reported as:
Mean · L/h
SU-011248 Clearance on Cycle 1 Day 28
L/hSU-011248 25-mgSU-011248 50-mg
SU-011248 Clearance on Cycle 1 Day 2843.1 ± 32.838.1 ± 11.6
PrimaryAccumulation Ratio (Rac) on Cycle 1 Day 28

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.

Time frame:
Day 28 of Cycle 1
Reported as:
Mean · ratio
Accumulation Ratio (Rac) on Cycle 1 Day 28
ratioSU-011248 25-mgSU-011248 50-mg
SU-011248: Rac Cmax3.32 ± 2.173.10 ± 0.77
SU-011248: Rac AUC0-244.31 ± 2.653.76 ± 0.82
SU-012662: Rac Cmax7.98 ± 4.919.00 ± 2.20
SU-012662: Rac AUC0-2410.4 ± 5.510.6 ± 3.5
SU-011248+SU-012662: Rac Cmax3.87 ± 2.363.93 ± 0.98
SU-011248+SU-012662: Rac AUC0-245.08 ± 2.744.85 ± 1.20
PrimaryNumber of Subjects With Clinical Benefit Response (CBR) Based on the Extramural Review Committee Assessment in Recommended Dose Group

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).

Time frame:
Day 28 of Cycles 1-4
Reported as:
Number · participants
Number of Subjects With Clinical Benefit Response (CBR) Based on the Extramural Review Committee Assessment in Recommended Dose Group
participantsSU-011248 50-mg
Total Number of Subjects with CR+PR+SD>=22weeks12
Complete Response (CR)0
Partial Response (PR)4
Stable Disease (SD) >= 22 weeks8
Statistical analysis
  • SU-011248 50-mg · Cbr rate (percentage): 40.0 · 95% CI 22.7 to 59.4The clinical benefit response (CBR) rate, defined as the percentage of the subjects confirmed with CR, PR, or SD\>=22 weeks on study according to Response Evaluation Criteria in Solid Tumors (RECIST).
SecondaryTime To Failure (TTF)

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.

Time frame:
From the first dose to Progressive Disease, Treatment discontinuation except completion of treatment, or Death due to cancer.
Reported as:
Median · Weeks
Time To Failure (TTF)
WeeksSU-011248 50-mg
Time To Failure (TTF)28.4 (21.9 to 46.1)
SecondaryOverall Survival Time

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.

Time frame:
From the first dose to death
Reported as:
Median · Weeks
Overall Survival Time
WeeksSU-011248 50-mg
Overall Survival Time62.0 (47.9 to 99.9)

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
SU-011248 25-mg—1/3 (33.3%)3/3 (100%)
SU-011248 50-mg—12/30 (40%)30/30 (100%)
SU-011248 75-mg—2/3 (66.7%)3/3 (100%)
Most frequent serious events
Showing 10 of 27
Most frequent serious events
EventSU-011248 25-mgSU-011248 50-mgSU-011248 75-mg
Abdominal painGastrointestinal disorders1/30/300/3
Anal abscessInfections and infestations0/30/301/3
Blood bilirubin increasedInvestigations0/30/301/3
Disseminated intravascular coagulationBlood and lymphatic system disorders0/30/301/3
HypoglycaemiaMetabolism and nutrition disorders0/31/301/3
SepsisInfections and infestations0/30/301/3
SubileusGastrointestinal disorders0/31/301/3
Platelet count decreasedInvestigations0/32/300/3
Altered state of consciousnessNervous system disorders0/31/300/3
CardiomyopathyCardiac disorders0/31/300/3
Most frequent other events
Showing 10 of 122
Most frequent other events
EventSU-011248 25-mgSU-011248 50-mgSU-011248 75-mg
AnorexiaMetabolism and nutrition disorders1/322/303/3
Blood alkaline phosphatase increasedInvestigations1/311/303/3
Blood amylase increasedInvestigations0/38/303/3
DiarrhoeaGastrointestinal disorders3/323/303/3
Haemoglobin decreasedInvestigations2/322/303/3
HaemorrhoidsGastrointestinal disorders0/32/303/3
NauseaGastrointestinal disorders2/315/303/3
Neutrophil count decreasedInvestigations3/328/303/3
Palmar-plantar erythrodysaesthesia syndromeSkin and subcutaneous tissue disorders2/326/303/3
Platelet count decreasedInvestigations2/326/303/3

Baseline characteristics

Age, Customized
Age, Customized(participants)SU-011248 25-mgSU-011248 50-mgSU-011248 75-mgTotal
18-44 years2204
45-64 years124126
>=65 years0426
Sex: Female, Male
Sex: Female, Male(Participants)SU-011248 25-mgSU-011248 50-mgSU-011248 75-mgTotal
Female111012
Male219324
Region of Enrollment
Region of Enrollment(participants)SU-011248 25-mgSU-011248 50-mgSU-011248 75-mgTotal
Japan330336
Eastern Cooperative Oncology Group (ECOG) Performance Status
Eastern Cooperative Oncology Group (ECOG) Performance Status(participants)SU-011248 25-mgSU-011248 50-mgSU-011248 75-mgTotal
0318223
1012113
08

Study locations

4 sites
  • Pfizer Investigational Site
    Kashiwa, Chiba, Japan
  • Pfizer Investigational Site
    Sapporo, Hokkaido, Japan
  • Pfizer Investigational Site
    Suita, Osaka, Japan
  • Pfizer Investigational Site
    Chuo-ku, Tokyo, Japan
09

References and documents

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Nov 13, 2009, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00457743
Lead sponsor
Pfizer
First posted
Apr 6, 2007
Start date
Jan 2005
Primary completion
Aug 2008
Completion
Aug 2008
Results posted
Nov 13, 2009
Last update
Nov 13, 2009

Study contacts

Pfizer CT.gov Call Center
study director · Pfizer

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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