Clinical trial NCT00091078 (phase 2, status: terminated)
Conditions: gastrointestinal stromal tumor
ICD codes: C49.A0, C49.A1, C49.A2, C49.A5, C49.A3, C49.A4, C49.A9
Drugs: imatinib mesylate
SMILES: CN1CCN(CC2=CC=C(C=C2)C(=O)NC2=CC(NC3=NC=CC(=N3)C3=CN=CC=C3)=C(C)C=C2)CC1
Eligibility criteria:

        Inclusion Criteria:

          -  A pre-imatinib paraffin block of tumor or 20 unstained slides should be submitted for
             correlative studies if available

          -  All patients must have either "limited" progression on imatinib (arm 1, some but not
             all tumor foci progressing and are not amenable to local therapy) or "generalized"
             progression (arm 2, widespread progression of all tumor foci) after adequate therapy
             with imatinib mesylate (> or = 400 mg/day for at least 6 weeks)

          -  Histologically confirmed diagnosis of Kit-expressing advanced GIST; advanced GIST is
             defined by patients who have disease that is unresectable; this includes patients with
             metastatic disease or primary tumors that cannot be safely removed by a sarcoma
             surgical oncologist

          -  Measurable disease by CT; tests used to assess disease must be done within 28 days
             prior to registration. If a targeted lesion has been previously embolized or
             irradiated, or if the patient has received imatinib, there must be objective evidence
             of progression to be considered for response assessment

          -  ECOG performance status 0-2

          -  At least 4 weeks and recovery from effects of prior therapy (i.e radiation,
             biotherapy, chemotherapy other than imatinib mesylate, or embolization;) recovery from
             the effects of prior therapy such that they are less than or equal to grade 1 in
             severity for non-hematological toxicities excluding nausea and vomiting controlled
             with standard anti-emetic regimens, alopecia, fatigue, and peripheral edema

          -  Absolute neutrophil count (ANC) >= 1000/mm3

          -  Platelets >= 100,000/mm3

          -  Serum creatinine =< 1.5 x ULN

          -  Serum bilirubin =< 1.5 x ULN

          -  Serum SGOT or SGPT =< 2.5 x ULN if no liver metastases or =< 5 x ULN if liver
             metastases are present

          -  PT and PTT =< 1.5 x ULN

          -  Understand and sign written informed consent in accordance with institutional and
             federal guidelines

          -  All patients must have progressive disease defined as 1) an increase in unidimensional
             tumor size of > or = 10% AND did not meet criteria for PR by CT density, 2) any new
             lesions, including new tumor nodules in a previous cystic tumor

          -  Patients with widespread metastatic and progressive disease will be eligible for this
             protocol

          -  Patients without widespread metastases will be evaluated by a sarcoma surgical
             oncologist to determine the benefit of and risk of surgical resection; if surgical
             resection is not recommended, the patient will be eligible for therapy with the study
             drug

          -  Pregnancy or lactation; women or men of reproductive potential must agree to use an
             effective barrier contraceptive method during treatment and for three months after the
             last dose of drug; women of reproductive potential must have a negative serum
             pregnancy test within 7 days prior to registration; post-menopausal women must be
             amenorrheic for at least 12 months to be considered of non-child bearing potential

        Exclusion Criteria:

          -  Significant concurrent medical disease other than cancer including:

               -  New York Heart Association class III or IV cardiac problems (e.g., congestive
                  heart failure, acute myocardial infarction within 2 months of study)

               -  Uncontrolled chronic renal or liver disease

               -  Uncontrolled diabetes

               -  Uncontrolled seizure disorder

               -  Active uncontrolled infection, e.g., HIV

               -  Organ allografts

          -  History of second cancer, except for adequately treated basal cell or squamous cell
             skin cancer, in situ cervical cancer, or other cancer for which the patient has been
             disease-free for 5 or more years