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

Pfizer36 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Gastrointestinal Stromal Tumors

Interventions

Sunitinib malate (SU011248)DRUG

SU011248

Eligibility

Sex: ALLMin age: 20 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Locations (4)

Pfizer Investigational Site

Kashiwa, Chiba, Japan

Pfizer Investigational Site

Sapporo, Hokkaido, Japan

Pfizer Investigational Site

Suita, Osaka, Japan

Pfizer Investigational Site

Chuo-ku, Tokyo, Japan

Outcomes

Primary Outcomes

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)

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

Maximum Plasma Concentration (Cmax) on Cycle 1 Day 28

Time frame: 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).

Time frame: Day 1 of Cycle 1

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

Data from ClinicalTrials.gov

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Secondary Outcomes

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

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

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

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

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

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

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

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

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

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

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

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

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.

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