Overview

To learn if regorafenib can help to control the disease.

Eligibility

Inclusion Criteria:

        Patients must have measurable disease, defined as at least one lesion that can be
        accurately measured in at least one dimension (longest diameter to be recorded for nonnodal
        lesions and short axis for nodal lesions) as≥10 mm (≥1 cm) with CT scan, MRI, or calipers
        by clinical exam.
          -  Age ≥18 years.
          -  Histologic diagnosis of GIST with presence of KIT exon 17, 18, or 14 mutation, or SDHB
             deficiency on tumor biopsy and/ or liquid biopsy.
          -  Participants must have unresectable or metastatic GIST and radiologic progression on
             imatinib treatment. Imatinib treatment must have been discontinued at least 5 days
             prior to the first dose of study drug. All imatinib treatment will be counted as 1
             line of therapy.
          -  ECOG performance status ≤2 (Karnofsky ≥60%) at screening.
          -  Life expectancy of at least 12 weeks (3 months).
          -  Subjects must be able to understand and be willing to sign the written informed
             consent form. A signed informed consent form must be appropriately obtained prior to
             the conduct of any trialspecific procedure.
          -  Patients must have adequate organ and marrow function as definedbelow:
        Hemoglobin ≥8 g/dL Absolute neutrophil count ≥1,000/mcL Platelets ≥100,000/mcL Total
        bilirubin ≤2 x institutional upper limit of normal (ULN) or <3 x ULN in the presence of
        Gilbert's Disease AST and ALT ≤3 × institutional ULN ALT and AST ≤ 2.5 x ULN (≤ 5 x ULN for
        subjects with liver involvement of their cancer) Alkaline phosphatase ≤ 2.5 x ULN (≤ 5 x
        ULN for subjects with liver involvement of their cancer) Serum creatinine ≤ 3 x the ULN or
        24-hr creatinine clearance >30 ml/min (Cockcroft formula) INR/ PTT ≤ 1.5 x ULN. (Subjects
        who are prophylactically treated with an agent such as warfarin or heparin will be allowed
        to participate provided that no prior evidence of underlying abnormality in coagulation
        parameters exists. Close monitoring of at least weekly evaluations will be performed until
        INR/PTT is stable based on a measurement that is pre-dose as defined by the local standard
        of care
          -  Women of childbearing potential must have a negative serum pregnancy test performed
             within 7 days prior to the start of study drug. Post-menopausal women (defined as no
             menses for at least
             1 year) and surgically sterilized women are not required to undergo a pregnancy test.
          -  Subjects (men and women) of childbearing potential must agree to use adequate
             contraception beginning at the signing of the ICF until at least 2 months after the
             last dose of study drug.
        Approved methods of birth control are as follows: Hormonal contraception (i.e. birth
        control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device
        (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or
        injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for
        the total duration of the trial and the drug washout period is an acceptable practice;
        however periodic abstinence, the rhythm method, and the withdrawal method are not
        acceptable methods of birth control. Should a woman become pregnant or suspect she is
        pregnant while she or her partner is participating in this study, she should inform her
        treating physician immediately
        • Subject must be able to swallow and retain oral medication.
        Exclusion Criteria:
          -  Patients who had received treatment with TKI other than imatinib
          -  Uncontrolled hypertension (systolic pressure >140 mm Hg or diastolic pressure > 90 mm
             Hg [NCI-CTCAE v4.0] on repeated measurement) despite optimal medical management.
          -  Active or clinically significant cardiac disease including:
               -  Congestive heart failure - New York Heart Association (NYHA) > Class II.
               -  Active coronary artery disease.
               -  Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or
                  digoxin.
               -  Unstable angina (anginal symptoms at rest), new-onset angina within 3 months
                  before randomization, or myocardial infarction within 6 months before
                  randomization.
          -  Evidence or history of bleeding diathesis or coagulopathy.
          -  Any hemorrhage or bleeding event ≥ NCI CTCAE v 5.0 Grade 3 within 4 weeks prior to
             start of study medication.
          -  Subjects with thrombotic, embolic, venous, or arterial events, such as cerebrovascular
             accident (including transient ischemic attacks) deep vein thrombosis or pulmonary
             embolism within 6 months of informed consent.
          -  Patients with any previously untreated or concurrent cancer that is distinct in
             primary site or histology except cervical cancer in-situ, treated ductal carcinoma in
             situ of the breast, curatively treated nonmelanoma skin carcinoma, noninvasive
             aerodigestive neoplasms, or superficial bladder tumor. Subjects surviving a cancer
             that was curatively treated and without evidence of disease for more than 3 years
             before registration are allowed. All cancer treatments must be completed at least 3
             years prior to registration.
          -  Patients with pheochromocytoma.
          -  Patients with evidence of chronic hepatitis B virus (HBV) infection (except HBV viral
             load is undetectable on suppressive therapy)
          -  Patients with a history of hepatitis C virus (HCV) infection (Except the patients have
             been treated and cured or are currently on treatment with an undetectable HCV viral
             load)
          -  Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
             therapy with undetectable viral load within 6 months are eligible for this trial.
          -  Ongoing infection > Grade 2 NCI-CTCAE v5.0.
          -  Symptomatic metastatic brain or meningeal tumors.
          -  Presence of a non-healing wound, non-healing ulcer, or bone fracture.
          -  Major surgical procedure or significant traumatic injury within 28 days before start
             of study medication (minor surgical procedures such as central venous catheter
             placement, tumour needle biopsy, and feeding tube placement are not considered major
             surgical procedures).
          -  Renal failure requiring hemo-or peritoneal dialysis.
          -  Dehydration Grade >1 NCI-CTCAE v5.0.
          -  Patients with seizure disorder requiring medication.
          -  Persistent proteinuria Grade 3 NCI-CTCAE v5.0 (> 3.5 g/24 hrs, measured by urine
             protein: creatinine ratio on a random urine sample).
          -  Interstitial lung disease with ongoing signs and symptoms at the time of informed
             consent.
          -  Pleural effusion or ascites that causes respiratory compromise (≥ NCI-CTCAE version
             5.0 Grade 2 dyspnea).
          -  History of organ allograft (including corneal transplant).
          -  Any malabsorption condition.
          -  Women who are pregnant or breast-feeding.
          -  Any condition which, in the investigator's opinion, makes the subject unsuitable for
             trial participation.
          -  Substance abuse, medical, psychological or social conditions that may interfere with
             the subject's participation in the study or evaluation of the study results.
          -  Pregnant women, as documented by a serum beta human chorionic gonadotropin (β-hCG)
             pregnancy test obtained within 7 days before treatment consistent with pregnancy, are
             excluded from this study because regorafenib has evidence of the potential for
             teratogenic or abortifacient effects in animal studies. Because there is an unknown
             but potential risk for adverse events in nursing infants secondary to treatment of the
             mother with regorafenib, breastfeeding should be discontinued if the mother is treated
             with regorafenib. Females of non-childbearing potential (postmenopausal for more than
             1 year; bilateral tubal ligation; bilateral oophorectomy; hysterectomy) do not require
             a serum β-hCG test.