Safety And Efficacy Study Of Sunitinib Malate In Chinese Patients With Imatinib Resistant Or Intolerant Malignant Gastrointestinal Stromal Tumor

Study Overview
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Brief Summary
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To investigate safety and efficacy of single agent sunitinib malate in Chinese Patients With Imatinib Resistant Or Intolerant Malignant Gastrointestinal Stromal Tumor.

Official Title
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A Single-arm, Open-label, Multi-center, Phase Iv, Efficacy And Safety Study Of Sunitinib Malate In The Treatment Of Chinese Patients With Gastrointestinal Stromal Tumor After Disease Progression On Or Intolerance To Imatinib Mesylate

Conditions
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Gastrointestinal Neoplasms, Gastrointestinal Stromal Tumors

Intervention / Treatment
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* Drug: Sunitinib Malate (SU011248)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically-proven diagnosis of malignant GIST (Gastrointestinal Stromal Tumors). Evidence of unidimensionally measurable disease Failure of prior treatment with imatinib or intolerant to imatinib Male or female, 18 years of age or older. ECOG (Eastern Cooperative Oncology Group) performance status 0 or 1. Resolution of all acute toxic effects Adequate organ function. Exclusion Criteria: Anticancer treatment after last dose of imatinib Major surgery within 4 weeks or radiation therapy within 2 weeks. Grade 3 hemorrhage within 4 weeks prior to starting the study treatment. Diagnosis of second malignancy within the last 5 years. History of brain disease. Cardiac disease within 12 months. Thyroid function abnormality. Ongoing cardiac dysrhythmias. Uncontrolled hypertension. Ongoing treatment with anticoagulant and CYP3A4 inhibitors and inducers. HIV or AIDS related illness. Pregnancy or breastfeeding.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: sunitinib<br>single agent sunitinib, single arm | Drug: Sunitinib Malate (SU011248)<br>* Subjects will receive treatment with sunitinib in repeated 6-week cycles (4 weeks on, 2 weeks off), at a starting dose of 50 mg.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | PFS was defined as the time (in weeks) from the date of the first treatment to the date of the first documentation of objective tumor progression or death due to any cause, whichever occurred first. Participants last known to be 1) alive, 2) on study treatment or discontinued study treatment, but haven't yet started a new anticancer treatment and 3) progression-free were censored at the date of the last objective disease assessment that verified lack of disease progression. Disease progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST version 1.0), as a >=20% increase in the sum of the longest dimensions of the target lesions taking as a reference the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of one or more new lesions. | Baseline (Day 1) up to disease progression or death whichever occurred first (up to 264 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS was defined as the time (in weeks) from the date of the first treatment to the date of death due to any cause. In the absence of confirmation of death, survival time was censored at the last date the participant was known to be alive. | Baseline (Day 1) to death (up to 282 weeks) | 
| Objective Response Rate (ORR) | ORR was defined as the proportion of participants who achieved an objective response. A participant was considered to have an objective response if a confirmed best response of complete response (CR) or partial response (PR) was achieved according to RECIST, version 1.0. CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeters (mm). PR is at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | Baseline (Day 1) up to end of study treatment (up to 276 weeks) | 
| Time to Tumor Progression (TTP) | TTP was defined as the time (in weeks) from the date of the first treatment to the date of the first documentation of objective tumor progression or death due to tumor progression. Participants last known to be 1) alive,2) on treatment or within 28 days of discontinuation from treatment and 3) progression-free were censored at the date of last objective disease assessment that verified lack of disease progression. Participants with no post baseline assessments were censored at the start date. Participants who died without prior objective disease progression and participants who discontinued treatment without objective disease progression within 28 days of last dose were censored at the date of the last objective disease assessment that verified lack of disease progression. Disease progression is defined using RECIST version 1.0. | Baseline (Day 1) up to objective tumor progression or death due to tumor progression (up to 264 weeks) | 
| Number of Participants With Abnormal Clinical Laboratory Measurements | The total number of participants with laboratory test abnormalities without regard to baseline abnormality was assessed. Laboratory parameters included hematology (hemoglobin, platelets, white blood cell count, lymphocytes, neutrophils, basophils, eosinophils and monocytes), liver function (total bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total protein and albumin), renal function (blood urea nitrogen, creatinine and uric acid), electrolytes (sodium, potassium, chloride, calcium, magnesium and phosphate), hormones (thyroxine and thyroid stimulating hormone), clinical chemistry (glucose), and urinalysis (urine protein) tests. | Baseline up to 28 days post last administration of study drug | 
| Number of Participants With Significant Changes From Baseline in Physical Examination. | Physical examinations including, but not limited to, general appearance, skin, neck, eyes, ears, nose, mouth, throat, breast, lungs, heart, abdomen, rectal, lymph nodes, extremities, thyroid, musculoskeletal, and nervous system were performed. | Baseline up to 28 days post last administration of study drug | 
| Number of Participants With Significant Vital Signs Changes From Baseline | Vital signs included blood pressure (BP), temperature, heart rate, respiration rate and body weight. The criteria for significant changes included BP: systolic BP (SBP) greater than (>) 150 millimeters of mercury (mm Hg) and/or diastolic BP (DBP) > 100 mm Hg, or SBP > 200 mm Hg and/or DBP > 110 mm Hg; temperature: >38.3 degrees Celsius (degrees C), or increase of greater than or equal to (>=)1.1 degrees C (baseline >=36.8 degrees C); heart rate: >120 beats per minute (bpm) or less than (<) 50 bpm, or increase of >=30 bpm or decrease of ≥30 bpm; respiration rate: > 40 /minute or < 8 /minute; weight: a change of 5% or more from baseline. | Baseline (Day 1) up to 28 days post last administration of study drug | 
| Eastern Cooperative Oncology Group (ECOG) Performance Status | ECOG was used to assess participants' performance status: 0 (Fully active, able to carry on all pre-disease activities without restriction); 1 (Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work or office work); 2 (Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours); 3 (Capable of only limited self-care, confined to bed or chair more than 50% of waking hours); 4 (Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair); and 5 (Dead). | Baseline (Day 1), Last-on treatment visit (up to 28 days post last administration of study drug) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sunitinib, Phase IV, gastrointestinal stomal tumor, imatinib resistant or intolerant, Chinese