Gastrointestinal Stromal Tumors
Conditions
Keywords
Evaluate of RTD for Japanese GIST patients
Brief 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.
Interventions
SU011248
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patients with histologically-confirmed metastatic or unresectable gastrointestinal stromal tumor (GIST). * Patients previously treated with imatinib mesylate.
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Dose Limiting Toxicities (DLT) | Cycle 1 (Baseline to Week 6) | Dose Limiting Toxicities(DLT) in the subjects enrolled in Phase 1. |
| Maximum Plasma Concentration (Cmax) on Cycle 1 Day 1 | Day 1 of Cycle 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). |
| Maximum Plasma Concentration (Cmax) on Cycle 1 Day 28 | Day 28 of Cycle 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). |
| Area Under the Plasma Concentration Curve (AUC0-24) on Cycle 1 Day 1 | Day 1 of Cycle 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). |
| Area Under the Plasma Concentration Curve (AUC0-24) on Cycle 1 Day 28 | Day 28 of Cycle 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 to First Occurrence of Cmax (Tmax) on Cycle 1 Day 1 | Day 1 of Cycle 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 to First Occurrence of Cmax (Tmax) on Cycle 1 Day 28 | Day 28 of Cycle 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 medians of Tmax of SU-011248 and SU-012662). |
| SU-011248 Clearance on Cycle 1 Day 28 | Day 28 of Cycle 1 | 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). |
| Accumulation Ratio (Rac) on Cycle 1 Day 28 | Day 28 of Cycle 1 | 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. |
| Number of Subjects With Clinical Benefit Response (CBR) Based on the Extramural Review Committee Assessment in Recommended Dose Group | Day 28 of Cycles 1-4 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time To Tumor Progression (TTP) | From the first dose to Progressive Disease | 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). |
| Progression-Free Survival (PFS) | From the first dose to Progressive Disease or Death | 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. |
| Plasma Concentrations of Vascular Endothelial Growth Factor (VEGF) | Day 1, 14, 28 of Cycles 1-4 | Plasma concentrations of potential pharmacodynamic markers; Vascular Endothelial Growth Factor (VEGF) |
| Overall Survival Time | From the first dose to death | 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 To Failure (TTF) | From the first dose to Progressive Disease, Treatment discontinuation except completion of treatment, or Death due to cancer. | 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. |
| Plasma Concentrations of Soluble Vascular Endothelial Growth Factor Type 2 Receptors (sVEGFR2) | Day 1, 14, 28 of Cycles 1-4 | Plasma concentrations of potential pharmacodynamic markers; Soluble Vascular Endothelial Growth Factor Type 2 Receptors (sVEGFR2) |
| Plasma Concentrations of Soluble Stem Cell Factor Receptor (sKIT) | Day 1, 14, 28 of Cycles 1-4 | Plasma concentrations of potential pharmacodynamic markers; Soluble Stem Cell Factor Receptor (sKIT) |
| Trough Plasma Concentration (Ctrough) of SU-011248 | Day 14, 28 of Cycle 1; Day 1, 14, 28 of Cycles 2-4 | Trough Plasma Concentration (Ctrough) means the concentration prior to study drug administration |
| Trough Plasma Concentration (Ctrough) of SU-012262 | Day 14, 28 of Cycle 1; Day 1, 14, 28 of Cycles 2-4 | Trough Plasma Concentration (Ctrough) means the concentration prior to study drug administration |
| Trough Plasma Concentration (Ctrough) of SU-011248+SU-012662 | Day 14, 28 of Cycle 1; Day 1, 14, 28 of Cycles 2-4 | Trough Plasma Concentration (Ctrough) means the concentration prior to study drug administration |
| Changes From Baseline of Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaires | Day 7, 14, 28, 35 of Cycle 1; Day 1, 7, 14, 28, 35 of Cycles 2-4 | 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 |
| Change From Baseline of European Quality of Life Questionnaire- 5 Dimensions(EQ-5D) Questionnaires | Day 28 of Cycle 1; Day 1, 28 of Cycles 2-4 | 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 |
| Number of Subjects With Disease Controlled Based on the Extramural Review Committee Assessment in Recommended Dose Group | Day 28 of Cycles 1-4 | 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). |
| Number of Subjects With Objective Response Based on the Extramural Review Committee Assessment in Recommended Dose Group | Day 28 of Cycles 1-4 | 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). |
Countries
Japan
Participant flow
Pre-assignment details
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).
Participants by arm
| Arm | Count |
|---|---|
| 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. | 3 |
| 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. | 30 |
| 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. | 3 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 4 | 0 |
| Overall Study | Lack of Efficacy | 3 | 23 | 3 |
Baseline characteristics
| Characteristic | SU-011248 25-mg | SU-011248 50-mg | SU-011248 75-mg | Total |
|---|---|---|---|---|
| Age, Customized 18-44 years | 2 participants | 2 participants | 0 participants | 4 participants |
| Age, Customized 45-64 years | 1 participants | 24 participants | 1 participants | 26 participants |
| Age, Customized >=65 years | 0 participants | 4 participants | 2 participants | 6 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0 | 3 participants | 18 participants | 2 participants | 23 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1 | 0 participants | 12 participants | 1 participants | 13 participants |
| Region of Enrollment Japan | 3 participants | 30 participants | 3 participants | 36 participants |
| Sex: Female, Male Female | 1 Participants | 11 Participants | 0 Participants | 12 Participants |
| Sex: Female, Male Male | 2 Participants | 19 Participants | 3 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 30 / 30 | 3 / 3 |
| serious Total, serious adverse events | 1 / 3 | 12 / 30 | 2 / 3 |
Outcome results
Primary
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
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SU-011248 25-mg | Accumulation Ratio (Rac) on Cycle 1 Day 28 | SU-011248: Rac Cmax | 3.32 ratio | Standard Deviation 2.17 |
| SU-011248 25-mg | Accumulation Ratio (Rac) on Cycle 1 Day 28 | SU-011248: Rac AUC0-24 | 4.31 ratio | Standard Deviation 2.65 |
| SU-011248 25-mg | Accumulation Ratio (Rac) on Cycle 1 Day 28 | SU-011248+SU-012662: Rac AUC0-24 | 5.08 ratio | Standard Deviation 2.74 |
| SU-011248 25-mg | Accumulation Ratio (Rac) on Cycle 1 Day 28 | SU-011248+SU-012662: Rac Cmax | 3.87 ratio | Standard Deviation 2.36 |
| SU-011248 25-mg | Accumulation Ratio (Rac) on Cycle 1 Day 28 | SU-012662: Rac Cmax | 7.98 ratio | Standard Deviation 4.91 |
| SU-011248 25-mg | Accumulation Ratio (Rac) on Cycle 1 Day 28 | SU-012662: Rac AUC0-24 | 10.4 ratio | Standard Deviation 5.5 |
| SU-011248 50-mg | Accumulation Ratio (Rac) on Cycle 1 Day 28 | SU-012662: Rac Cmax | 9.00 ratio | Standard Deviation 2.2 |
| SU-011248 50-mg | Accumulation Ratio (Rac) on Cycle 1 Day 28 | SU-011248: Rac Cmax | 3.10 ratio | Standard Deviation 0.77 |
| SU-011248 50-mg | Accumulation Ratio (Rac) on Cycle 1 Day 28 | SU-011248: Rac AUC0-24 | 3.76 ratio | Standard Deviation 0.82 |
| SU-011248 50-mg | Accumulation Ratio (Rac) on Cycle 1 Day 28 | SU-011248+SU-012662: Rac Cmax | 3.93 ratio | Standard Deviation 0.98 |
| SU-011248 50-mg | Accumulation Ratio (Rac) on Cycle 1 Day 28 | SU-011248+SU-012662: Rac AUC0-24 | 4.85 ratio | Standard Deviation 1.2 |
| SU-011248 50-mg | Accumulation Ratio (Rac) on Cycle 1 Day 28 | SU-012662: Rac AUC0-24 | 10.6 ratio | Standard Deviation 3.5 |
Primary
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
Population: All enrolled subjects who received at least 1 dose of study medication and who had at least 1 blood concentration data for Pharmacokinetic analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SU-011248 25-mg | Area Under the Plasma Concentration Curve (AUC0-24) on Cycle 1 Day 1 | SU-011248+SU-012662 | 230 ng•h/mL | Standard Deviation 108 |
| SU-011248 25-mg | Area Under the Plasma Concentration Curve (AUC0-24) on Cycle 1 Day 1 | SU-012662 | 30.9 ng•h/mL | Standard Deviation 20.6 |
| SU-011248 25-mg | Area Under the Plasma Concentration Curve (AUC0-24) on Cycle 1 Day 1 | SU-011248 | 199 ng•h/mL | Standard Deviation 89 |
| SU-011248 50-mg | Area Under the Plasma Concentration Curve (AUC0-24) on Cycle 1 Day 1 | SU-011248+SU-012662 | 444 ng•h/mL | Standard Deviation 82 |
| SU-011248 50-mg | Area Under the Plasma Concentration Curve (AUC0-24) on Cycle 1 Day 1 | SU-011248 | 374 ng•h/mL | Standard Deviation 69 |
| SU-011248 50-mg | Area Under the Plasma Concentration Curve (AUC0-24) on Cycle 1 Day 1 | SU-012662 | 70.0 ng•h/mL | Standard Deviation 14.4 |
| SU-011248 75-mg | Area Under the Plasma Concentration Curve (AUC0-24) on Cycle 1 Day 1 | SU-011248+SU-012662 | 599 ng•h/mL | Standard Deviation 287 |
| SU-011248 75-mg | Area Under the Plasma Concentration Curve (AUC0-24) on Cycle 1 Day 1 | SU-012662 | 91.1 ng•h/mL | Standard Deviation 45.3 |
| SU-011248 75-mg | Area Under the Plasma Concentration Curve (AUC0-24) on Cycle 1 Day 1 | SU-011248 | 508 ng•h/mL | Standard Deviation 259 |
Primary
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
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SU-011248 25-mg | Area Under the Plasma Concentration Curve (AUC0-24) on Cycle 1 Day 28 | SU-011248 | 858 ng•h/mL | Standard Deviation 600 |
| SU-011248 25-mg | Area Under the Plasma Concentration Curve (AUC0-24) on Cycle 1 Day 28 | SU-012662 | 324 ng•h/mL | Standard Deviation 223 |
| SU-011248 25-mg | Area Under the Plasma Concentration Curve (AUC0-24) on Cycle 1 Day 28 | SU-011248+SU-012662 | 1182 ng•h/mL | Standard Deviation 734 |
| SU-011248 50-mg | Area Under the Plasma Concentration Curve (AUC0-24) on Cycle 1 Day 28 | SU-011248 | 1406 ng•h/mL | Standard Deviation 364 |
| SU-011248 50-mg | Area Under the Plasma Concentration Curve (AUC0-24) on Cycle 1 Day 28 | SU-012662 | 772 ng•h/mL | Standard Deviation 358 |
| SU-011248 50-mg | Area Under the Plasma Concentration Curve (AUC0-24) on Cycle 1 Day 28 | SU-011248+SU-012662 | 2178 ng•h/mL | Standard Deviation 702 |
Primary
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
Population: All enrolled subjects who received at least 1 dose of study medication and who had at least 1 blood concentration data for Pharmacokinetic analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SU-011248 25-mg | Maximum Plasma Concentration (Cmax) on Cycle 1 Day 1 | SU-011248 | 12.1 ng/mL | Standard Deviation 4.9 |
| SU-011248 25-mg | Maximum Plasma Concentration (Cmax) on Cycle 1 Day 1 | SU-012662 | 1.96 ng/mL | Standard Deviation 1.27 |
| SU-011248 25-mg | Maximum Plasma Concentration (Cmax) on Cycle 1 Day 1 | SU-011248+SU-012662 | 14.1 ng/mL | Standard Deviation 6.1 |
| SU-011248 50-mg | Maximum Plasma Concentration (Cmax) on Cycle 1 Day 1 | SU-012662 | 4.13 ng/mL | Standard Deviation 0.93 |
| SU-011248 50-mg | Maximum Plasma Concentration (Cmax) on Cycle 1 Day 1 | SU-011248+SU-012662 | 26.7 ng/mL | Standard Deviation 7.4 |
| SU-011248 50-mg | Maximum Plasma Concentration (Cmax) on Cycle 1 Day 1 | SU-011248 | 22.8 ng/mL | Standard Deviation 6.4 |
| SU-011248 75-mg | Maximum Plasma Concentration (Cmax) on Cycle 1 Day 1 | SU-011248 | 32.3 ng/mL | Standard Deviation 20.8 |
| SU-011248 75-mg | Maximum Plasma Concentration (Cmax) on Cycle 1 Day 1 | SU-011248+SU-012662 | 37.0 ng/mL | Standard Deviation 22.1 |
| SU-011248 75-mg | Maximum Plasma Concentration (Cmax) on Cycle 1 Day 1 | SU-012662 | 4.81 ng/mL | Standard Deviation 2.54 |
Primary
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
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SU-011248 25-mg | Maximum Plasma Concentration (Cmax) on Cycle 1 Day 28 | SU-011248 | 39.5 ng/mL | Standard Deviation 25 |
| SU-011248 25-mg | Maximum Plasma Concentration (Cmax) on Cycle 1 Day 28 | SU-011248+SU-012662 | 54.0 ng/mL | Standard Deviation 32.2 |
| SU-011248 25-mg | Maximum Plasma Concentration (Cmax) on Cycle 1 Day 28 | SU-012662 | 15.2 ng/mL | Standard Deviation 10.2 |
| SU-011248 50-mg | Maximum Plasma Concentration (Cmax) on Cycle 1 Day 28 | SU-011248 | 69.3 ng/mL | Standard Deviation 18.9 |
| SU-011248 50-mg | Maximum Plasma Concentration (Cmax) on Cycle 1 Day 28 | SU-012662 | 38.8 ng/mL | Standard Deviation 16 |
| SU-011248 50-mg | Maximum Plasma Concentration (Cmax) on Cycle 1 Day 28 | SU-011248+SU-012662 | 105 ng/mL | Standard Deviation 35 |
Primary
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
Population: Intent-to-Treat (ITT) population defined as all subjects enrolled in study that receive at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SU-011248 25-mg | 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 |
| SU-011248 25-mg | Number of Subjects With Clinical Benefit Response (CBR) Based on the Extramural Review Committee Assessment in Recommended Dose Group | Complete Response (CR) | 0 participants |
| SU-011248 25-mg | Number of Subjects With Clinical Benefit Response (CBR) Based on the Extramural Review Committee Assessment in Recommended Dose Group | Partial Response (PR) | 4 participants |
| SU-011248 25-mg | 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 |
95% CI: [22.7, 59.4]
Primary
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)
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SU-011248 25-mg | Number of Subjects With Dose Limiting Toxicities (DLT) | 0 participants |
| SU-011248 50-mg | Number of Subjects With Dose Limiting Toxicities (DLT) | 0 participants |
| SU-011248 75-mg | Number of Subjects With Dose Limiting Toxicities (DLT) | 2 participants |
Primary
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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SU-011248 25-mg | SU-011248 Clearance on Cycle 1 Day 28 | 43.1 L/h | Standard Deviation 32.8 |
| SU-011248 50-mg | SU-011248 Clearance on Cycle 1 Day 28 | 38.1 L/h | Standard Deviation 11.6 |
Primary
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
Population: All enrolled subjects who received at least 1 dose of study medication and who had at least 1 blood concentration data for Pharmacokinetic analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| SU-011248 25-mg | Time to First Occurrence of Cmax (Tmax) on Cycle 1 Day 1 | SU-011248+SU-012662 | 6 hours |
| SU-011248 25-mg | Time to First Occurrence of Cmax (Tmax) on Cycle 1 Day 1 | SU-012662 | 6 hours |
| SU-011248 25-mg | Time to First Occurrence of Cmax (Tmax) on Cycle 1 Day 1 | SU-011248 | 6 hours |
| SU-011248 50-mg | Time to First Occurrence of Cmax (Tmax) on Cycle 1 Day 1 | SU-011248+SU-012662 | 7 hours |
| SU-011248 50-mg | Time to First Occurrence of Cmax (Tmax) on Cycle 1 Day 1 | SU-012662 | 9 hours |
| SU-011248 50-mg | Time to First Occurrence of Cmax (Tmax) on Cycle 1 Day 1 | SU-011248 | 7 hours |
| SU-011248 75-mg | Time to First Occurrence of Cmax (Tmax) on Cycle 1 Day 1 | SU-011248+SU-012662 | 8 hours |
| SU-011248 75-mg | Time to First Occurrence of Cmax (Tmax) on Cycle 1 Day 1 | SU-012662 | 10 hours |
| SU-011248 75-mg | Time to First Occurrence of Cmax (Tmax) on Cycle 1 Day 1 | SU-011248 | 8 hours |
Primary
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
Population: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| SU-011248 25-mg | Time to First Occurrence of Cmax (Tmax) on Cycle 1 Day 28 | SU-012662 | 4 hours |
| SU-011248 25-mg | Time to First Occurrence of Cmax (Tmax) on Cycle 1 Day 28 | SU-011248+SU-012662 | 6 hours |
| SU-011248 25-mg | Time to First Occurrence of Cmax (Tmax) on Cycle 1 Day 28 | SU-011248 | 10 hours |
| SU-011248 50-mg | Time to First Occurrence of Cmax (Tmax) on Cycle 1 Day 28 | SU-012662 | 2.5 hours |
| SU-011248 50-mg | Time to First Occurrence of Cmax (Tmax) on Cycle 1 Day 28 | SU-011248+SU-012662 | 6 hours |
| SU-011248 50-mg | Time to First Occurrence of Cmax (Tmax) on Cycle 1 Day 28 | SU-011248 | 6 hours |
Secondary
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
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SU-011248 25-mg | 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 |
| SU-011248 25-mg | 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 |
| SU-011248 25-mg | 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 |
| SU-011248 25-mg | 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 |
| SU-011248 25-mg | 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 0.21 |
| SU-011248 25-mg | 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 |
| SU-011248 25-mg | 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
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
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SU-011248 25-mg | 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 |
| SU-011248 25-mg | 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 |
| SU-011248 25-mg | 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 |
| SU-011248 25-mg | 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 |
| SU-011248 25-mg | 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 |
| SU-011248 25-mg | 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 |
| SU-011248 25-mg | 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 |
| SU-011248 25-mg | 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 |
| SU-011248 25-mg | 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 |
| SU-011248 25-mg | 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 |
| SU-011248 25-mg | 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 |
| SU-011248 25-mg | 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 |
| SU-011248 25-mg | 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 |
| SU-011248 25-mg | 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 |
| SU-011248 25-mg | 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 |
| SU-011248 25-mg | 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 |
| SU-011248 25-mg | 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 |
| SU-011248 25-mg | 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 |
| SU-011248 25-mg | 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 |
| SU-011248 25-mg | 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 |
| SU-011248 25-mg | 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 |
| SU-011248 25-mg | 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 |
| SU-011248 25-mg | 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
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
Population: Intent-to-Treat (ITT) population defined as all subjects enrolled in study that receive at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SU-011248 25-mg | 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 |
| SU-011248 25-mg | Number of Subjects With Disease Controlled Based on the Extramural Review Committee Assessment in Recommended Dose Group | Complete Response (CR) | 0 participants |
| SU-011248 25-mg | Number of Subjects With Disease Controlled Based on the Extramural Review Committee Assessment in Recommended Dose Group | Partial Response (PR) | 4 participants |
| SU-011248 25-mg | Number of Subjects With Disease Controlled Based on the Extramural Review Committee Assessment in Recommended Dose Group | Stable Disease (SD) >= 10 weeks | 13 participants |
95% CI: [37.4, 74.5]
Secondary
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
Population: ITT population defined as all subjects enrolled in study that receive at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SU-011248 25-mg | 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 |
| SU-011248 25-mg | Number of Subjects With Objective Response Based on the Extramural Review Committee Assessment in Recommended Dose Group | Complete Response (CR) | 0 participants |
| SU-011248 25-mg | Number of Subjects With Objective Response Based on the Extramural Review Committee Assessment in Recommended Dose Group | Partial Response (PR) | 4 participants |
95% CI: [3.8, 30.7]
Secondary
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
Population: Intent-to-Treat (ITT) population defined as all subjects enrolled in study that receive at least 1 dose of study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SU-011248 25-mg | Overall Survival Time | 62.0 Weeks |
Secondary
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
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SU-011248 25-mg | Plasma Concentrations of Soluble Stem Cell Factor Receptor (sKIT) | Cycle 4 Day 28 (n=9) | 32571.11 pg/mL | Standard Deviation 20949.63 |
| SU-011248 25-mg | Plasma Concentrations of Soluble Stem Cell Factor Receptor (sKIT) | Cycle 1 Day 1 (n=30) | 48237.33 pg/mL | Standard Deviation 56643.93 |
| SU-011248 25-mg | Plasma Concentrations of Soluble Stem Cell Factor Receptor (sKIT) | Cycle 1 Day 14 (n=30) | 53087.75 pg/mL | Standard Deviation 71243.85 |
| SU-011248 25-mg | Plasma Concentrations of Soluble Stem Cell Factor Receptor (sKIT) | Cycle 1 Day 28 (n=19) | 35538.95 pg/mL | Standard Deviation 16082.33 |
| SU-011248 25-mg | Plasma Concentrations of Soluble Stem Cell Factor Receptor (sKIT) | Cycle 2 Day 1 (n=26) | 39011.35 pg/mL | Standard Deviation 38304.6 |
| SU-011248 25-mg | Plasma Concentrations of Soluble Stem Cell Factor Receptor (sKIT) | Cycle 3 Day 14 (n=19) | 32973.68 pg/mL | Standard Deviation 14483.42 |
| SU-011248 25-mg | Plasma Concentrations of Soluble Stem Cell Factor Receptor (sKIT) | Cycle 3 Day 28 (n=13) | 32760.77 pg/mL | Standard Deviation 16888.75 |
| SU-011248 25-mg | Plasma Concentrations of Soluble Stem Cell Factor Receptor (sKIT) | Cycle 4 Day 1 (n=11) | 28961.82 pg/mL | Standard Deviation 14899.42 |
| SU-011248 25-mg | Plasma Concentrations of Soluble Stem Cell Factor Receptor (sKIT) | Cycle 4 Day 14 (n=12) | 32265.83 pg/mL | Standard Deviation 16143.54 |
| SU-011248 25-mg | Plasma Concentrations of Soluble Stem Cell Factor Receptor (sKIT) | Cycle 2 Day 14 (n=24) | 40432.29 pg/mL | Standard Deviation 45085.57 |
| SU-011248 25-mg | Plasma Concentrations of Soluble Stem Cell Factor Receptor (sKIT) | Cycle 2 Day 28 (n=20) | 30715.75 pg/mL | Standard Deviation 16212.04 |
| SU-011248 25-mg | Plasma Concentrations of Soluble Stem Cell Factor Receptor (sKIT) | Cycle 3 Day 1 (n=18) | 27814.17 pg/mL | Standard Deviation 10362.85 |
Secondary
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
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SU-011248 25-mg | 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 |
| SU-011248 25-mg | 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 |
| SU-011248 25-mg | 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 |
| SU-011248 25-mg | 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 |
| SU-011248 25-mg | 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 |
| SU-011248 25-mg | 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 |
| SU-011248 25-mg | 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 |
| SU-011248 25-mg | 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 |
| SU-011248 25-mg | Plasma Concentrations of Soluble Vascular Endothelial Growth Factor Type 2 Receptors (sVEGFR2) | Cycle 2 Day 14 (n=24) | 5808.08 pg/mL | Standard Deviation 1484.3 |
| SU-011248 25-mg | 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 |
| SU-011248 25-mg | 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 |
| SU-011248 25-mg | 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 |
Secondary
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
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SU-011248 25-mg | Plasma Concentrations of Vascular Endothelial Growth Factor (VEGF) | Cycle 1 Day 1 (n=30) | 55.30 pg/mL | Standard Deviation 32.43 |
| SU-011248 25-mg | Plasma Concentrations of Vascular Endothelial Growth Factor (VEGF) | Cycle 1 Day 14 (n=30) | 179.94 pg/mL | Standard Deviation 116 |
| SU-011248 25-mg | Plasma Concentrations of Vascular Endothelial Growth Factor (VEGF) | Cycle 2 Day 28 (n=20) | 207.79 pg/mL | Standard Deviation 158.05 |
| SU-011248 25-mg | Plasma Concentrations of Vascular Endothelial Growth Factor (VEGF) | Cycle 3 Day 1 (n=18) | 58.80 pg/mL | Standard Deviation 26.13 |
| SU-011248 25-mg | Plasma Concentrations of Vascular Endothelial Growth Factor (VEGF) | Cycle 3 Day 14 (n=19) | 208.93 pg/mL | Standard Deviation 159.41 |
| SU-011248 25-mg | Plasma Concentrations of Vascular Endothelial Growth Factor (VEGF) | Cycle 3 Day 28 (n=13) | 238.74 pg/mL | Standard Deviation 227.63 |
| SU-011248 25-mg | Plasma Concentrations of Vascular Endothelial Growth Factor (VEGF) | Cycle 4 Day 1 (n=11) | 54.83 pg/mL | Standard Deviation 14.86 |
| SU-011248 25-mg | Plasma Concentrations of Vascular Endothelial Growth Factor (VEGF) | Cycle 1 Day 28 (n=19) | 192.42 pg/mL | Standard Deviation 210.58 |
| SU-011248 25-mg | Plasma Concentrations of Vascular Endothelial Growth Factor (VEGF) | Cycle 2 Day 1 (n=26) | 62.05 pg/mL | Standard Deviation 38.2 |
| SU-011248 25-mg | Plasma Concentrations of Vascular Endothelial Growth Factor (VEGF) | Cycle 2 Day 14 (n=24) | 173.12 pg/mL | Standard Deviation 96.3 |
| SU-011248 25-mg | Plasma Concentrations of Vascular Endothelial Growth Factor (VEGF) | Cycle 4 Day 14 (n=12) | 227.28 pg/mL | Standard Deviation 163.52 |
| SU-011248 25-mg | Plasma Concentrations of Vascular Endothelial Growth Factor (VEGF) | Cycle 4 Day 28 (n=9) | 343.21 pg/mL | Standard Deviation 210.28 |
Secondary
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
Population: Intent-to-Treat (ITT) population defined as all subjects enrolled in study that receive at least 1 dose of study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SU-011248 25-mg | Progression-Free Survival (PFS) | 30.3 Weeks |
Secondary
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.
Population: Intent-to-Treat (ITT) population defined as all subjects enrolled in study that receive at least 1 dose of study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SU-011248 25-mg | Time To Failure (TTF) | 28.4 Weeks |
Secondary
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
Population: Intent-to-Treat (ITT) population defined as all subjects enrolled in study that receive at least 1 dose of study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SU-011248 25-mg | Time To Tumor Progression (TTP) | 30.3 Weeks |
Secondary
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
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SU-011248 25-mg | Trough Plasma Concentration (Ctrough) of SU-011248 | Cycle 1 Day 14 (n=28) | 58.93 ng/mL | Standard Deviation 23.87 |
| SU-011248 25-mg | Trough Plasma Concentration (Ctrough) of SU-011248 | Cycle 1 Day 28 (n=18) | 44.52 ng/mL | Standard Deviation 15.45 |
| SU-011248 25-mg | Trough Plasma Concentration (Ctrough) of SU-011248 | Cycle 2 Day 1 (n=15) | 1.17 ng/mL | Standard Deviation 0.6 |
| SU-011248 25-mg | Trough Plasma Concentration (Ctrough) of SU-011248 | Cycle 3 Day 14 (n=14) | 58.72 ng/mL | Standard Deviation 27.09 |
| SU-011248 25-mg | Trough Plasma Concentration (Ctrough) of SU-011248 | Cycle 3 Day 28 (n=10) | 47.13 ng/mL | Standard Deviation 21.73 |
| SU-011248 25-mg | Trough Plasma Concentration (Ctrough) of SU-011248 | Cycle 4 Day 1 (n=5) | 1.52 ng/mL | Standard Deviation 0.81 |
| SU-011248 25-mg | Trough Plasma Concentration (Ctrough) of SU-011248 | Cycle 4 Day 14 (n=7) | 46.13 ng/mL | Standard Deviation 22.28 |
| SU-011248 25-mg | Trough Plasma Concentration (Ctrough) of SU-011248 | Cycle 4 Day 28 (n=8) | 47.33 ng/mL | Standard Deviation 12.95 |
| SU-011248 25-mg | Trough Plasma Concentration (Ctrough) of SU-011248 | Cycle 2 Day 14 (n=23) | 51.23 ng/mL | Standard Deviation 16.98 |
| SU-011248 25-mg | Trough Plasma Concentration (Ctrough) of SU-011248 | Cycle 2 Day 28 (n=20) | 48.09 ng/mL | Standard Deviation 22.41 |
| SU-011248 25-mg | Trough Plasma Concentration (Ctrough) of SU-011248 | Cycle 3 Day 1 (n=11) | 1.62 ng/mL | Standard Deviation 0.88 |
Secondary
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
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SU-011248 25-mg | Trough Plasma Concentration (Ctrough) of SU-011248+SU-012662 | Cycle 4 Day 28 (n=8) | 73.26 ng/mL | Standard Deviation 24.82 |
| SU-011248 25-mg | Trough Plasma Concentration (Ctrough) of SU-011248+SU-012662 | Cycle 1 Day 14 (n=28) | 85.33 ng/mL | Standard Deviation 36.59 |
| SU-011248 25-mg | Trough Plasma Concentration (Ctrough) of SU-011248+SU-012662 | Cycle 1 Day 28 (n=18) | 69.05 ng/mL | Standard Deviation 27.52 |
| SU-011248 25-mg | Trough Plasma Concentration (Ctrough) of SU-011248+SU-012662 | Cycle 2 Day 1 (n=15) | 3.18 ng/mL | Standard Deviation 1.45 |
| SU-011248 25-mg | Trough Plasma Concentration (Ctrough) of SU-011248+SU-012662 | Cycle 2 Day 14 (n=23) | 75.29 ng/mL | Standard Deviation 27.35 |
| SU-011248 25-mg | Trough Plasma Concentration (Ctrough) of SU-011248+SU-012662 | Cycle 2 Day 28 (n=20) | 72.56 ng/mL | Standard Deviation 36.14 |
| SU-011248 25-mg | Trough Plasma Concentration (Ctrough) of SU-011248+SU-012662 | Cycle 3 Day 1 (n=11) | 3.88 ng/mL | Standard Deviation 1.88 |
| SU-011248 25-mg | Trough Plasma Concentration (Ctrough) of SU-011248+SU-012662 | Cycle 3 Day 14 (n=14) | 86.41 ng/mL | Standard Deviation 42.83 |
| SU-011248 25-mg | Trough Plasma Concentration (Ctrough) of SU-011248+SU-012662 | Cycle 3 Day 28 (n=10) | 70.96 ng/mL | Standard Deviation 32.81 |
| SU-011248 25-mg | Trough Plasma Concentration (Ctrough) of SU-011248+SU-012662 | Cycle 4 Day 1 (n=5) | 3.54 ng/mL | Standard Deviation 1.46 |
| SU-011248 25-mg | Trough Plasma Concentration (Ctrough) of SU-011248+SU-012662 | Cycle 4 Day 14 (n=7) | 65.99 ng/mL | Standard Deviation 33.42 |
Secondary
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
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SU-011248 25-mg | Trough Plasma Concentration (Ctrough) of SU-012262 | Cycle 1 Day 14 (n=28) | 26.41 ng/mL | Standard Deviation 15.86 |
| SU-011248 25-mg | Trough Plasma Concentration (Ctrough) of SU-012262 | Cycle 1 Day 28 (n=18) | 24.52 ng/mL | Standard Deviation 13.28 |
| SU-011248 25-mg | Trough Plasma Concentration (Ctrough) of SU-012262 | Cycle 2 Day 1 (n=15) | 2.01 ng/mL | Standard Deviation 0.9 |
| SU-011248 25-mg | Trough Plasma Concentration (Ctrough) of SU-012262 | Cycle 2 Day 14 (n=23) | 24.06 ng/mL | Standard Deviation 11.54 |
| SU-011248 25-mg | Trough Plasma Concentration (Ctrough) of SU-012262 | Cycle 2 Day 28 (n=20) | 24.47 ng/mL | Standard Deviation 14.92 |
| SU-011248 25-mg | Trough Plasma Concentration (Ctrough) of SU-012262 | Cycle 3 Day 1 (n=11) | 2.26 ng/mL | Standard Deviation 1.2 |
| SU-011248 25-mg | Trough Plasma Concentration (Ctrough) of SU-012262 | Cycle 3 Day 14 (n=14) | 27.69 ng/mL | Standard Deviation 16.34 |
| SU-011248 25-mg | Trough Plasma Concentration (Ctrough) of SU-012262 | Cycle 3 Day 28 (n=10) | 23.83 ng/mL | Standard Deviation 12.59 |
| SU-011248 25-mg | Trough Plasma Concentration (Ctrough) of SU-012262 | Cycle 4 Day 1 (n=5) | 2.02 ng/mL | Standard Deviation 0.9 |
| SU-011248 25-mg | Trough Plasma Concentration (Ctrough) of SU-012262 | Cycle 4 Day 14 (n=7) | 19.86 ng/mL | Standard Deviation 11.38 |
| SU-011248 25-mg | Trough Plasma Concentration (Ctrough) of SU-012262 | Cycle 4 Day 28 (n=8) | 25.94 ng/mL | Standard Deviation 12.28 |