Regorafenib in Patients With Metastatic and/or Unresectable Gastrointestinal Stromal Tumor
Condition: Gastrointestinal Stromal Tumor
MeSH terms: Gastrointestinal Stromal Tumors
Intervention: regorafenib
Intervention description: Taken orally, once a day in the morning for 3 weeks followed by a one week rest period
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 34.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: regorafenib; GIST

Summary:

      The purpose of this research study is to determine the safety and activity of regorafenib in
      participants with advanced gastrointestinal stromal tumor (GIST) if the standard approved
      therapies, imatinib and sunitinib, have failed to control the disease. Regorafenib is a drug
      that blocks abnormally active signaling enzymes called "tyrosine kinases" which are important
      to the growth of GIST. This "tyrosine kinase inhibition" is similar to the way that both
      imatinib and sunitinib work; however, regorafenib blocks certain additional signaling
      pathways that are not blocked by imatinib or sunitinib. Regorafenib has been not been tested
      in GIST participants before this research study.
    

Eligibility criteria:

        Inclusion Criteria:

          -  At least 18 years of age at the time of study entry

          -  Histologically confirmed metastatic and/or unresectable GIST with prior failure of
             both conventional tyrosine kinase inhibitors, imatinib and sunitinib.

          -  Measurable disease per RECIST 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.

          -  ECOG Performance Status 0 or 1

          -  Adequate organ and marrow function as outlined in the protocol

          -  Fully recovered from the acute effects of prior cancer therapy before initiation of
             study drug

          -  Patients must be suitable for oral drug administration

          -  Willingness to use effective means of birth control throughout the duration of
             clinical study and for at least 3 months after completion of study drug

          -  Women of childbearing potential must have a negative pregnancy test performed within 7
             days of the start of study drug administration

        Exclusion Criteria:

          -  Use of any unapproved tyrosine kinase inhibitors or investigational agents within 2
             weeks or 6 half-lives of the agent, whichever is shorter, prior to receiving study
             drug

          -  Participants who have had radiotherapy within 4 weeks prior to study entry

          -  Major surgery, or significant traumatic injury within 4 weeks prior to study entry

          -  Presence of symptomatic or uncontrolled brain or central nervous system metastases

          -  Prior exposure to sorafenib

          -  Prior exposure to regorafenib

          -  Known or suspected allergy to the investigational agent or any agent given in
             association with this trial

          -  Individuals with a history of a different malignancy, other than cervical cancer in
             situ, basal cell or squamous cell carcinoma of the skin, are ineligible, except if
             they have been disease-free for at least 5 years, and are deemed by the investigator
             to be at low risk for recurrence of that malignancy or other primary malignancy is
             neither currently clinically significant nor requiring active intervention

          -  Clinically significant cardiac arrhythmias and/or patients who require anti-arrhythmic
             therapy (excluding beta blockers or digoxin)

          -  History of clinically significant cardiac disease or congestive heart failure > NYHA
             class 2. Patients must not have unstable angina or new-onset angina within the last 3
             months or myocardial infarction within the past 6 months

          -  Hypertension as defined by systolic blood pressure 140-159 mmHg or diastolic blood
             pressure 90-99 mmHg; recurrent or persistent or symptomatic increase by > 20 mmHg
             (diastolic) or to systolic blood pressure greater than 140 mmHg or diastolic blood
             pressure greater than 90 mmHg if previously within normal limits, 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 the 6 months before start of study medication

          -  Ongoing infection of Grade 3 or higher

          -  Patients with evidence of, or history of, bleeding diathesis. Any major hemorrhage or
             bleeding event of Grade 3 or higher within 4 weeks of start of study medication

          -  Non-healing wound, ulcer or bone fracture

          -  Renal failure requiring hemo-or peritoneal dialysis

          -  Dehydration of Grade 2 or greater

          -  Persistent proteinuria Grade 3 or higher

          -  Known history of HIV infection or chronic hepatitis B or C

          -  Uncontrolled intercurrent illness

          -  Pregnant or lactating females