Regorafenib in GIST With Secondary C-KIT Exon 17 Mutation

Study Overview
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Brief Summary
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The main purpose of this study is to examine whether regorafenib treatment can help people with gastrointestinal stromal tumours (GIST) and have gene mutation on c-kit exon 17. The safety of regorafenib treatment is also examined.

Official Title
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A Phase 2 Study of Regorafenib in Metastatic Gastrointestinal Stromal Tumours With C-KIT exon17 Mutation

Conditions
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Gastrointestinal Stromal Tumour (GIST)

Intervention / Treatment
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* Drug: regorafenib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: An eligible subject must fulfill all of the following inclusion criteria: Signed informed consent (IC) obtained before any study specific procedure. Patients must be able to understand and willing to sign the written IC. Pathologically confirmed gastrointestinal stromal tumours. All patients had received imatinib or sunitinib. Pathological confirmed c-kit exon 17 mutation. At least one measurable lesion in a non-irradiated area or allowed to be tracked whether there are circumstances recurrence by computed tomography (CT) or magnetic resonance imaging (MRI). Aged > 20 years old. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. Life expectancy greater than 12 weeks. Adequate bone marrow function: 1) Absolutely neutrophil count >= 1.5 x10^9/L or white blood cell count (WBC) >= 4x10^9/L; 2) Hemoglobin >= 9 g/dL; 3) Platelet count >= 100x10^9/L. Adequate liver function: 1) Total bilirubin <= 1.5x the upper limit of normal (ULN); 2) Alanine Aminotransferase (ALT) & Aspartate Aminotransferase (AST) <= 2.5x ULN if without liver metastasis or <= 5x ULN if with hepatic metastasis; 3) Alkaline phosphatase <= 2.5x ULN if without liver metastasis or <= 5x ULN if with hepatic metastasis or bone metastasis; 4) Bilirubin < 2x ULN. Adequate renal function: creatinine <1.5x ULN. Patients must be accessible for treatment and follow-up in the participating centers. Exclusion Criteria: Subject will not meet any of the following exclusion criteria: Major surgery within four weeks prior to entering the study. Patients with central nervous system (CNS) metastasis, including clinical suspicion. Patients who are under active or uncontrolled infections. Patients who with unstable angina (angina symptoms at rest, new-onset angina (begun within the last 3 months) or myocardial infarction history 6 months before entry. Cardiac arrhythmia requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted). Congestive heart failure New York Heart Association (NYHA) class 2. Uncontrolled hypertension (systolic blood pressure [BP] > 150 mmHg or diastolic pressure > 90 mmHg despite optimal medical management. Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 months before the start of study medication. Patients who are pregnant or with breast feeding. Other concomitant or previously malignancy within 5 years except for in situ cervix cancer or squamous cell carcinoma of the skin treated by surgery only. Mental status is not fit for clinical trial. Cannot take study medication orally. Fertile men and women unless using a reliable and appropriate contraceptive method. Patients with evidence or history of any bleeding diathesis, irrespective of severity. Any hemorrhage or bleeding event >= Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 within 4 weeks prior to the start of study medication. Non-healing wound, ulcer, or bone fracture. Renal failure requiring hemo-or peritoneal dialysis.

Ages Eligible for Study
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Minimum Age: 20 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: regorafenib<br>regorafenib 160 mg daily, 3 weeks on/1 week off | Drug: regorafenib<br> <br> * Other names: stivarga;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall clinical benefit rate | complete response (CR), partial response (PR), and stable disease (SD) | till 2 weeks after last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) |  | till study end, estimated 3 years | 
| Overall survival (OS) |  | till study end, estimated 3 years |