A Clinical Trial Evaluating the Efficacy and Safety of Dasatinib in Refractory Metastatic GIST

Study Overview
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Brief Summary
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The purpose of this study is to determine whether dasatinib is effective and safe in the treatment of refractory metastatic gastrointestinal stromal tumor

Official Title
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A Prospective, Single-arm, Multi-center Clinical Trial Evaluating the Efficacy and Safety of Dasatinib in RefrActory MetAstatic Gastrointestinal Stromal Tumor

Conditions
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Gastrointestinal Stromal Tumor

Intervention / Treatment
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* Drug: dasatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed recurrent/metastatic gastrointestinal stromal tumor (GIST). Immunohistochemically, the detection KIT and/or DOG-1 are/is positive Patients must have measurable disease meeting the requirement of RECIST 1.1 Received the gene mutation detection of c - kit/PDGFRA Subjects with mutation in exon 11, in exon 9 and wild type c-kit/PDGFRA have failed to imatinib and sunitinib Subjects with primary mutation in exon 17 or 18 have failed to imatinib Subjects with primary mutation in exon 11 and secondary mutation in exon 17 or 18 have failed to imatinib Subjects with mutation in exon 18 of PDGFRA,have received TKI or not Eastern Cooperative Oncology Group (ECOG) performance status = 0-2 Expected OS ≥3 months Ability to understand and the willingness to sign a written informed consent document Subject will comply with the study procedures and therapy Exclusion Criteria: Local or metastatic GIST is resectable Unable to receive the gene mutation detection of c-kit (c-kitproto-oncogeneprotein)/PDGFRA AST and/or ALT > 2.5 times ULN, or Bilirubin >1.5 times upper limit of normal (ULN) Neutrophil count < 1.5 x 10^9/L, or Platelet count <75 x 10^9/L, or Hemoglobin<90g/L Cr >1.5×ULN Other malignancy within the past 5 years except for adequately treated carcinoma in situ of the cervix or cutaneous basal cell carcinoma Known brain metastasis, spinal cord compression, carcinomatous meningitis, or cerebral or soft meningeal disease through CT or MRI during screening stage Within the past 5 years, subjects have one of the following disease: myocardial infarction, serious/instable angina pectoris, symptomatic congestive heart failure or cerebrovascular accident from coronary/peripheral artery bypass grafting Known human immunodeficiency virus positivity Joining in other trail Women who are pregnant or lactating; No contraception for subject during childbearing period Subject with other serious acute and chronic physical or mental problems, or laboratory abnormality, will increase the risks associated with trail or drug. It will also interference the judgment of the results. In the judgment of the investigator, subject is inadequate to participant the study

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: Dasatinib<br>Dasatinib is given orally 50 mg 2 times a day for the first week, if subject is tolerate, then increased to 70 mg 2 times a day. Dasatinib will be continued until unacceptable toxicity and progression. | Drug: dasatinib<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survive, calculated from registration until progression or death |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival, overall survival will be calculated from registration until death |  | 2 years | 
| Adverse drug reactions according to NCI CTCAE v4.0 |  | 2 years, Tolerability will be assessed based on the frequency and severity of Adverse Drug Reactions (ADR) coded according to NCI CTCAE v4.0. | 
| Objective response, according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria |  | 2 years | 
| Tumor control probability, defined as CR＋PR＋SD, determined according to RECIST 1.1 criteria |  | 2 years |