Back to resultsA Phase I/II Study of Sunitinib Malate (SU011248) In Patients With Gastrointestinal Stromal Tumor (GIST)
Primary Purpose
Gastrointestinal Stromal Tumors
Status
Completed
Phase
Phase 1
Locations
Japan
Study Type
Interventional
Intervention
Sunitinib malate (SU011248)
Sponsored by
About this trial
This is an interventional treatment trial for Gastrointestinal Stromal Tumors focused on measuring Evaluate of RTD for Japanese GIST patients
Eligibility Criteria
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.
Sites / Locations
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
SU011248
Arm Description
25 , 50 or 75 mg/day of SU011248
Outcomes
Primary Outcome Measures
Number of Subjects With Dose Limiting Toxicities (DLT)
Dose Limiting Toxicities(DLT) in the subjects enrolled in Phase 1.
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).
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).
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).
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 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 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).
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).
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.
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).
Secondary Outcome Measures
Plasma Concentrations of Vascular Endothelial Growth Factor (VEGF)
Plasma concentrations of potential pharmacodynamic markers; Vascular Endothelial Growth Factor (VEGF)
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)
Plasma Concentrations of Soluble Stem Cell Factor Receptor (sKIT)
Plasma concentrations of potential pharmacodynamic markers; Soluble Stem Cell Factor Receptor (sKIT)
Trough Plasma Concentration (Ctrough) of SU-011248
Trough Plasma Concentration (Ctrough) means the concentration prior to study drug administration
Trough Plasma Concentration (Ctrough) of SU-012262
Trough Plasma Concentration (Ctrough) means the concentration prior to study drug administration
Trough Plasma Concentration (Ctrough) of SU-011248+SU-012662
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
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
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
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
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 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).
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 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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00457743
Brief Title
A Phase I/II Study of Sunitinib Malate (SU011248) In Patients With Gastrointestinal Stromal Tumor (GIST)
Official Title
A Phase I/II Study of Sunitinib Malate (SU011248) In The Treatment of Patients With Malignant Gastrointestinal Stromal Tumor (GIST) Previously Treated by Imatinib Mesylate.
Study Type
Interventional
2. Study Status
Record Verification Date
October 2009
Overall Recruitment Status
Completed
Study Start Date
January 2005 (undefined)
Primary Completion Date
August 2008 (Actual)
Study Completion Date
August 2008 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Pfizer
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastrointestinal Stromal Tumors
Keywords
Evaluate of RTD for Japanese GIST patients
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
36 (Actual)
8. Arms, Groups, and Interventions
Arm Title
SU011248
Arm Type
Experimental
Arm Description
25 , 50 or 75 mg/day of SU011248
Intervention Type
Drug
Intervention Name(s)
Sunitinib malate (SU011248)
Intervention Description
SU011248
Primary Outcome Measure Information:
Title
Number of Subjects With Dose Limiting Toxicities (DLT)
Description
Dose Limiting Toxicities(DLT) in the subjects enrolled in Phase 1.
Time Frame
Cycle 1 (Baseline to Week 6)
Title
Maximum Plasma Concentration (Cmax) on Cycle 1 Day 1
Description
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
Title
Maximum Plasma Concentration (Cmax) on Cycle 1 Day 28
Description
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
Title
Area Under the Plasma Concentration Curve (AUC0-24) on Cycle 1 Day 1
Description
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
Title
Area Under the Plasma Concentration Curve (AUC0-24) on Cycle 1 Day 28
Description
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
Title
Time to First Occurrence of Cmax (Tmax) on Cycle 1 Day 1
Description
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
Title
Time to First Occurrence of Cmax (Tmax) on Cycle 1 Day 28
Description
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
Title
SU-011248 Clearance on Cycle 1 Day 28
Description
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
Title
Accumulation Ratio (Rac) on Cycle 1 Day 28
Description
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
Title
Number of Subjects With Clinical Benefit Response (CBR) Based on the Extramural Review Committee Assessment in Recommended Dose Group
Description
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 Outcome Measure Information:
Title
Plasma Concentrations of Vascular Endothelial Growth Factor (VEGF)
Description
Plasma concentrations of potential pharmacodynamic markers; Vascular Endothelial Growth Factor (VEGF)
Time Frame
Day 1, 14, 28 of Cycles 1-4
Title
Plasma Concentrations of Soluble Vascular Endothelial Growth Factor Type 2 Receptors (sVEGFR2)
Description
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
Title
Plasma Concentrations of Soluble Stem Cell Factor Receptor (sKIT)
Description
Plasma concentrations of potential pharmacodynamic markers; Soluble Stem Cell Factor Receptor (sKIT)
Time Frame
Day 1, 14, 28 of Cycles 1-4
Title
Trough Plasma Concentration (Ctrough) of SU-011248
Description
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
Title
Trough Plasma Concentration (Ctrough) of SU-012262
Description
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
Title
Trough Plasma Concentration (Ctrough) of SU-011248+SU-012662
Description
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
Title
Changes From Baseline of Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Questionnaires
Description
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
Title
Change From Baseline of European Quality of Life Questionnaire- 5 Dimensions(EQ-5D) Questionnaires
Description
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
Title
Number of Subjects With Disease Controlled Based on the Extramural Review Committee Assessment in Recommended Dose Group
Description
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
Title
Number of Subjects With Objective Response Based on the Extramural Review Committee Assessment in Recommended Dose Group
Description
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
Title
Time To Tumor Progression (TTP)
Description
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
Title
Progression-Free Survival (PFS)
Description
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
Title
Time To Failure (TTF)
Description
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.
Title
Overall Survival Time
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Pfizer Investigational Site
City
Kashiwa
State/Province
Chiba
Country
Japan
Facility Name
Pfizer Investigational Site
City
Sapporo
State/Province
Hokkaido
Country
Japan
Facility Name
Pfizer Investigational Site
City
Suita
State/Province
Osaka
Country
Japan
Facility Name
Pfizer Investigational Site
City
Chuo-ku
State/Province
Tokyo
Country
Japan
12. IPD Sharing Statement
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=A6181045&StudyName=A%20Phase%20I/II%20Study%20of%20%20Sunitinib%20malate%20%28SU011248%29%20In%20Patients%20with%20Gastrointestinal%20Stromal%20Tumor%20%28GIST%29%20%20
Description
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Learn more about this trial
A Phase I/II Study of Sunitinib Malate (SU011248) In Patients With Gastrointestinal Stromal Tumor (GIST)
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