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

Phase 1

Completed

• Conditions: Gastrointestinal Stromal Tumors
• Interventions: Drug: Sunitinib malate (SU011248)

• Registration Number: NCT00457743
• Lead Sponsor: Pfizer

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2005-01
• Study First Submitted: 2007-04-04
• Study First Submitted QC: 2007-04-04
• Study First Posted: 2007-04-06
• Primary Completion: 2008-08
• Study Completion: 2008-08
• Results First Submitted: 2009-07-16
• Status Verified: 2009-10
• Results First Submitted QC: 2009-10-02
• Last Update Submitted: 2009-10-02
• Results First Posted: 2009-11-13
• Last Update Posted: 2009-11-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
SU011248	Sunitinib malate (SU011248)	25 , 50 or 75 mg/day of SU011248

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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)
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).
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.
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.
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.

Trial Locations

Locations (1)

Pfizer Investigational Site; 🇯🇵 Chuo-ku, Tokyo, Japan