Clinical trial NCT02606097: Regorafenib in GIST With Secondary C-KIT Exon 17 Mutation
Official title: A Phase 2 Study of Regorafenib in Metastatic Gastrointestinal Stromal Tumours With C-KIT exon17 Mutation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gastrointestinal Stromal Tumour (GIST)
Lead sponsor: Chang Gung Memorial Hospital
Sponsor class: OTHER
First posted: 2015-11-17
Enrollment: 19
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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 criteria: 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.

Primary outcomes:
measure: Overall clinical benefit rate
timeFrame: till 2 weeks after last dose
Secondary outcomes:
measure: Progression free survival (PFS)
timeFrame: till study end, estimated 3 years
measure: Overall survival (OS)
timeFrame: till study end, estimated 3 years
Other outcomes:
measure: Adverse events (AEs)
timeFrame: till 2 weeks after last dose
measure: Changes in clinical hematology laboratory result by hemoglobin (Hb)
timeFrame: till 2 weeks after last dose
measure: Changes in clinical hematology laboratory result by hematocrit (Hct)
timeFrame: till 2 weeks after last dose
measure: Changes in clinical hematology laboratory result by platelet count
timeFrame: till 2 weeks after last dose
measure: Changes in clinical hematology laboratory result by red blood cell (RBC) count
timeFrame: till 2 weeks after last dose
measure: Changes in clinical hematology laboratory result by white blood cell (WBC) count
timeFrame: till 2 weeks after last dose
measure: Clinical hematology laboratory result by WBC differential
timeFrame: till 2 weeks after last dose
measure: Changes in clinical biochemistry laboratory result by potassium level
timeFrame: till 2 weeks after last dose
measure: Changes in clinical biochemistry laboratory result by calcium level
timeFrame: till 2 weeks after last dose
measure: Changes in clinical biochemistry laboratory result by glucose level
timeFrame: till 2 weeks after last dose
measure: Changes in clinical biochemistry laboratory result by lactate dehydrogenase (LDH) level
timeFrame: till 2 weeks after last dose
measure: Changes in clinical biochemistry laboratory result by blood urea nitrogen (BUN) level
timeFrame: till 2 weeks after last dose
measure: Changes in clinical biochemistry laboratory result by creatinine level
timeFrame: till 2 weeks after last dose
measure: Changes in clinical biochemistry laboratory result by total and direct bilirubin levels
timeFrame: till 2 weeks after last dose
measure: Changes in clinical biochemistry laboratory result by albumin levels
timeFrame: till 2 weeks after last dose
measure: Changes in clinical biochemistry laboratory result by alanine aminotransferase(ALT) levels
timeFrame: till 2 weeks after last dose
measure: Changes in clinical biochemistry laboratory result by aspartate aminotransferase (AST) levels
timeFrame: till 2 weeks after last dose
measure: Changes in clinical biochemistry laboratory result by alkaline phosphatase (ALP) level
timeFrame: till 2 weeks after last dose
measure: Changes in clinical biochemistry laboratory result by thyroid-stimulating hormone (TSH) level
timeFrame: till 2 weeks after last dose
measure: Changes in clinical biochemistry laboratory result by T3 level
timeFrame: till 2 weeks after last dose
measure: Changes in clinical biochemistry laboratory result by T4 level
timeFrame: till 2 weeks after last dose
measure: Changes in clinical urinalysis result by WBC count
timeFrame: till 2 weeks after last dose
measure: Changes in clinical urinalysis result by RBC count
timeFrame: till 2 weeks after last dose
measure: Changes in clinical urinalysis result by pH level
timeFrame: till 2 weeks after last dose
measure: Changes in clinical urinalysis result by protein level
timeFrame: till 2 weeks after last dose
measure: Changes in clinical urinalysis result by glucose level
timeFrame: till 2 weeks after last dose
measure: Changes in clinical coagulation results by prothrombin time (PT)
timeFrame: till 2 weeks after last dose
measure: Changes in clinical coagulation results by activated partial thromboplastin time (APTT)
timeFrame: till 2 weeks after last dose
measure: Changes in clinical coagulation results by international normalized ratio (INR)
timeFrame: till 2 weeks after last dose
measure: Physical examination
timeFrame: till 2 weeks after last dose
measure: Changes in vital signs by respiratory rate
timeFrame: till 2 weeks after last dose
measure: Changes in vital signs by pulse rate
timeFrame: till 2 weeks after last dose
measure: Changes in vital signs by systolic blood pressure
timeFrame: till 2 weeks after last dose
measure: Changes in vital signs by diastolic blood pressure
timeFrame: till 2 weeks after last dose
measure: Changes in vital signs by body temperature
timeFrame: till 2 weeks after last dose
Locations:
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital
Study officials:
affiliation: Professor and Chief, Department of Surgery
name: Chun-Nan Yeh, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Yeh CN, Chen MH, Chen YY, Yang CY, Yen CC, Tzen CY, Chen LT, Chen JS. A phase II trial of regorafenib in patients with metastatic and/or a unresectable gastrointestinal stromal tumor harboring secondary mutations of exon 17. Oncotarget. 2017 Jul 4;8(27):44121-44130. doi: 10.18632/oncotarget.17310.