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

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.

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.

Study Overview

• Status: Completed
• Conditions: Gastrointestinal Stromal Tumors
• Intervention / Treatment: Drug: Sunitinib malate (SU011248)

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SU011248; 25 , 50 or 75 mg/day of SU011248	Drug: Sunitinib malate (SU011248); SU011248

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Dose Limiting Toxicities (DLT)	Dose Limiting Toxicities(DLT) in the subjects enrolled in Phase 1.	Cycle 1 (Baseline to Week 6)
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).	Day 1 of Cycle 1
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).	Day 28 of Cycle 1
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).	Day 1 of Cycle 1
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).	Day 28 of Cycle 1
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).	Day 1 of Cycle 1
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).	Day 28 of Cycle 1
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).	Day 28 of Cycle 1
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.	Day 28 of Cycle 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).	Day 28 of Cycles 1-4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Concentrations of Vascular Endothelial Growth Factor (VEGF)	Plasma concentrations of potential pharmacodynamic markers; Vascular Endothelial Growth Factor (VEGF)	Day 1, 14, 28 of Cycles 1-4
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)	Day 1, 14, 28 of Cycles 1-4
Plasma Concentrations of Soluble Stem Cell Factor Receptor (sKIT)	Plasma concentrations of potential pharmacodynamic markers; Soluble Stem Cell Factor Receptor (sKIT)	Day 1, 14, 28 of Cycles 1-4
Trough Plasma Concentration (Ctrough) of SU-011248	Trough Plasma Concentration (Ctrough) means the concentration prior to study drug administration	Day 14, 28 of Cycle 1; Day 1, 14, 28 of Cycles 2-4
Trough Plasma Concentration (Ctrough) of SU-012262	Trough Plasma Concentration (Ctrough) means the concentration prior to study drug administration	Day 14, 28 of Cycle 1; Day 1, 14, 28 of Cycles 2-4
Trough Plasma Concentration (Ctrough) of SU-011248+SU-012662	Trough Plasma Concentration (Ctrough) means the concentration prior to study drug administration	Day 14, 28 of Cycle 1; Day 1, 14, 28 of Cycles 2-4
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	Day 7, 14, 28, 35 of Cycle 1; Day 1, 7, 14, 28, 35 of Cycles 2-4
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	Day 28 of Cycle 1; Day 1, 28 of Cycles 2-4
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).	Day 28 of Cycles 1-4
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).	Day 28 of Cycles 1-4
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).	From the first dose to Progressive Disease
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.	From the first dose to Progressive Disease 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.	From the first dose to Progressive Disease, Treatment discontinuation except completion of treatment, or 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.	From the first dose to death

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: January 1, 2005
• Primary Completion (Actual): August 1, 2008
• Study Completion (Actual): August 1, 2008

Study Registration Dates

• First Submitted: April 4, 2007
• First Submitted That Met QC Criteria: April 4, 2007
• First Posted (Estimate): April 6, 2007

Study Record Updates

• Last Update Posted (Estimate): November 13, 2009
• Last Update Submitted That Met QC Criteria: October 2, 2009
• Last Verified: October 1, 2009

More Information

Terms related to this study

• Keywords: Evaluate of RTD for Japanese GIST patients
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Neoplasms, Connective Tissue; Gastrointestinal Stromal Tumors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Sunitinib
• Other Study ID Numbers: A6181045; JapicCTI-070386