A Randomized, Double-blind, Placebo-controlled Phase III Study of Regorafenib Plus Best Supportive Care Versus Placebo Plus Best Supportive Care for Subjects With Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (GIST) Whose Disease Has Progressed Despite Prior Treatment With at Least Imatinib and Sunitinib
- Male or female subjects 18 years of age.
- Subjects with histologically confirmed metastatic and/or unresectable GIST.
- At least imatinib and sunitinib as prior treatment regimens, with objective disease
progression or intolerance to imatinib, as well as disease progression while on
sunitinib therapy. Additionally, disease progression or intolerance to other
systemic therapies, as well as investigational new agents, is allowed, except prior
treatment with any other vascular endothelial growth factor receptor (VEGFR)
- Subjects must have at least one measurable lesion according to Response Evaluation
Criteria in Solid Tumors (RECIST), version 1.1. A lesion in a previously irradiated
area is eligible to be considered as measurable disease as long as there is objective
evidence of progression of the lesion prior to study enrollment.
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
- Adequate bone marrow, liver, and renal function as assessed by laboratory parameters.
Recovery to NCI-CTCAE v4.0 Grade 0 or 1 level or recovery to baseline preceding the prior
treatment from any previous drug/procedure-related toxicity (except alopecia and anemia).
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
before start of study medication.
- Congestive heart failure New York Heart Association (NYHA) class 2.
- Unstable angina (angina symptoms at rest, new-onset angina, ie, within the last 3
months) or myocardial infarction (MI) within the past 6 months before start of study
- Uncontrolled hypertension (systolic blood pressure 140 mmHg or diastolic pressure 90
mmHg despite optimal medical management).
Arterial thrombotic or embolic events such as cerebrovascular accident (including
transient ischemic attacks), or pulmonary embolism within the 6 months before start of
study drug or venous thrombotic events such as deep vein thrombosis within the 3 months
before start of study drug.
- Ongoing infection grade 2 National Cancer Institute-Common Terminology Criteria for
Adverse Events (NCI CTCAE) version 4.0.
Symptomatic metastatic brain or meningeal tumors.
- Subjects with evidence or history of bleeding diathesis. Any hemorrhage or bleeding
event NCI-CTCAE version 4.0 grade 3 or higher within 4 weeks prior to the start of
Non-healing wound, ulcer, or bone fracture.
- Persistent proteinuria of NCI-CTCAE version 4.0 grade 3 or higher (3.5 g/24 hrs,
measured by urine protein:creatinine ratio on a random urine sample).