Regorafenib in GIST With Secondary C-KIT Exon 17 Mutation

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

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.

Study Overview

• Status: Completed
• Conditions: Gastrointestinal Stromal Tumour (GIST)
• Intervention / Treatment: Drug: regorafenib

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• Taiwan
  • Taoyuan, Taiwan, 333
    • Chang Gung Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: regorafenib; regorafenib 160 mg daily, 3 weeks on/1 week off	Drug: regorafenib; Other Names: stivarga

What is the study measuring?

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	Time Frame
Progression free survival (PFS)	till study end, estimated 3 years
Overall survival (OS)	till study end, estimated 3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events (AEs)	Incidence of AEs will be shown and severity will be graded using NCI-CTCAE version 4.0	till 2 weeks after last dose
Changes in clinical hematology laboratory result by hemoglobin (Hb)	(unit: g/dL)	till 2 weeks after last dose
Changes in clinical hematology laboratory result by hematocrit (Hct)	(unit: %)	till 2 weeks after last dose
Changes in clinical hematology laboratory result by platelet count	(unit: 10^9/L)	till 2 weeks after last dose
Changes in clinical hematology laboratory result by red blood cell (RBC) count	(unit: 10^9/L)	till 2 weeks after last dose
Changes in clinical hematology laboratory result by white blood cell (WBC) count	(unit: 10^9/L)	till 2 weeks after last dose
Clinical hematology laboratory result by WBC differential	(unit: %)	till 2 weeks after last dose
Changes in clinical biochemistry laboratory result by potassium level	(unit: mmol/L)	till 2 weeks after last dose
Changes in clinical biochemistry laboratory result by calcium level	(unit: mmol/L)	till 2 weeks after last dose
Changes in clinical biochemistry laboratory result by glucose level	(unit: mmol/L)	till 2 weeks after last dose
Changes in clinical biochemistry laboratory result by lactate dehydrogenase (LDH) level	(unit: U/L)	till 2 weeks after last dose
Changes in clinical biochemistry laboratory result by blood urea nitrogen (BUN) level	(unit: mmol/L)	till 2 weeks after last dose
Changes in clinical biochemistry laboratory result by creatinine level	(unit: mg/dL)	till 2 weeks after last dose
Changes in clinical biochemistry laboratory result by total and direct bilirubin levels	(unit: mg/dL)	till 2 weeks after last dose
Changes in clinical biochemistry laboratory result by albumin levels	(unit: g/L)	till 2 weeks after last dose
Changes in clinical biochemistry laboratory result by alanine aminotransferase(ALT) levels	(unit: U/L)	till 2 weeks after last dose
Changes in clinical biochemistry laboratory result by aspartate aminotransferase (AST) levels	(unit: U/L)	till 2 weeks after last dose
Changes in clinical biochemistry laboratory result by alkaline phosphatase (ALP) level	(unit: U/L)	till 2 weeks after last dose
Changes in clinical biochemistry laboratory result by thyroid-stimulating hormone (TSH) level	(unit: mIU/L)	till 2 weeks after last dose
Changes in clinical biochemistry laboratory result by T3 level	(unit: mIU/L)	till 2 weeks after last dose
Changes in clinical biochemistry laboratory result by T4 level	(unit: mIU/L)	till 2 weeks after last dose
Changes in clinical urinalysis result by WBC count	(unit: 10^9/L)	till 2 weeks after last dose
Changes in clinical urinalysis result by RBC count	(unit: 10^9/L)	till 2 weeks after last dose
Changes in clinical urinalysis result by pH level		till 2 weeks after last dose
Changes in clinical urinalysis result by protein level		till 2 weeks after last dose
Changes in clinical urinalysis result by glucose level	(unit: mmol/L)	till 2 weeks after last dose
Changes in clinical coagulation results by prothrombin time (PT)	(unit: sec)	till 2 weeks after last dose
Changes in clinical coagulation results by activated partial thromboplastin time (APTT)	(unit: sec)	till 2 weeks after last dose
Changes in clinical coagulation results by international normalized ratio (INR)		till 2 weeks after last dose
Physical examination		till 2 weeks after last dose
Changes in vital signs by respiratory rate	(unit: times/min)	till 2 weeks after last dose
Changes in vital signs by pulse rate	(unit: times/min)	till 2 weeks after last dose
Changes in vital signs by systolic blood pressure	(unit: mmHg)	till 2 weeks after last dose
Changes in vital signs by diastolic blood pressure	(unit: mmHg)	till 2 weeks after last dose
Changes in vital signs by body temperature	(unit: degree celsius)	till 2 weeks after last dose

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital
• Investigators: Principal Investigator: Chun-Nan Yeh, MD, Professor and Chief, Department of Surgery

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2014
• Primary Completion (Actual): May 1, 2018
• Study Completion (Actual): May 1, 2018

Study Registration Dates

• First Submitted: November 12, 2015
• First Submitted That Met QC Criteria: November 13, 2015
• First Posted (Estimate): November 17, 2015

Study Record Updates

• Last Update Posted (Actual): March 21, 2019
• Last Update Submitted That Met QC Criteria: March 19, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Neoplasms, Connective Tissue; Gastrointestinal Stromal Tumors
• Other Study ID Numbers: 17298