Patient case: 70-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (V654A)

Clinical trial: Regorafenib in GIST With Secondary C-KIT Exon 17 Mutation

Summary: 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.


Eligibility: 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.

Relevance to patient case: possibly relevant