Sorafenib in Treating Patients With Malignant Gastrointestinal Stromal Tumor That Progressed During or After Previous Treatment With Imatinib Mesylate and Sunitinib Malate
Condition: Gastrointestinal Stromal Tumor
MeSH terms: Gastrointestinal Stromal Tumors
Intervention: Sorafenib Tosylate
Intervention MeSH terms: Sorafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 38.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well sorafenib works in treating patients with malignant
      gastrointestinal stromal tumor that progressed during or after previous treatment with
      imatinib mesylate and sunitinib malate. Sorafenib may stop the growth of tumor cells by
      blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed gastrointestinal stromal tumor

               -  Not amenable to curative surgery

          -  Kit-expressing tumor

          -  Disease progression (i.e., new lesion or 20% increase in unidimensional tumor size) on
             or after treatment with imatinib mesylate and sunitinib malate

          -  Measurable disease, defined as ≥ 1 unidimensionally measurable lesion > 20 mm by
             conventional techniques OR > 10 mm by spiral CT scan

               -  Only site of measurable disease must be outside of previously irradiated area

          -  No known brain metastases

          -  Performance status - ECOG 0-2

          -  More than 3 months

          -  Absolute neutrophil count > 1,500/mm^3

          -  Platelet count > 100,000/mm^3

          -  Bilirubin normal

          -  AST and ALT < 2.5 times upper limit of normal

          -  Creatinine ≤ 1.5 mg/dL

          -  Creatinine clearance > 60 mL/min

          -  No symptomatic congestive heart failure

          -  No unstable angina pectoris

          -  No cardiac arrhythmia

          -  No uncontrolled hypertension

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  No other malignancy within the past 5 years except nonmelanoma skin cancer or
             carcinoma in situ of the cervix

          -  No history of allergic reaction attributed to compounds of similar chemical or
             biological composition to sorafenib

          -  No ongoing or active infection

          -  No psychiatric illness or social situation that would preclude study compliance

          -  No other uncontrolled illness

          -  No evidence of bowel perforation or obstruction

          -  No prior angiogenesis inhibitors

          -  No immunotherapy after the last dose of imatinib mesylate or sunitinib malate

          -  No chemotherapy or chemoembolization therapy after the last dose of imatinib mesylate
             or sunitinib malate

          -  See Disease Characteristics

          -  At least 4 weeks since prior radiotherapy and recovered

          -  At least 14 days since prior imatinib mesylate or sunitinib malate

          -  No prior sorafenib

          -  No prior inhibitors of MAPK-signaling intermediates

          -  No other investigational agent after the last dose of imatinib mesylate or sunitinib
             malate

          -  Concurrent anticoagulation therapy with warfarin allowed provided the following
             criteria are met:

               -  On a therapeutic stable warfarin dose

               -  INR ≤3

               -  No active bleeding or pathologic condition that confers a high risk of bleeding

          -  No concurrent combination antiretroviral therapy for HIV-positive patients

          -  No concurrent administration of any of the following:

               -  Enzyme-inducing antiepileptic drugs (e.g., carbamazepine, phenytoin, or
                  phenobarbital)

               -  Hypericum perforatum (St. John's wort)

               -  Rifampin

          -  No other concurrent anticancer agents or therapies