Sunitinib in Treating Patients With Recurrent Malignant Gliomas
Condition: Adult Anaplastic Astrocytoma; Adult Diffuse Astrocytoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Pineal Gland Astrocytoma
MeSH terms: Glioblastoma; Glioma; Astrocytoma; Gliosarcoma; Oligodendroglioma
Intervention: sunitinib malate; pharmacological study
Intervention description: Given orally; Correlative studies
Intervention MeSH terms: Sunitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 31.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well sunitinib works in treating patients with recurrent
      malignant gliomas. Sunitinib 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:

          -  Stratum 1:

               -  Currently not receiving an enzyme-inducing anticonvulsant

                    -  Patients receiving non-enzyme inducing anticonvulsants are eligible for this
                       stratum

               -  Histologically confirmed WHO grade IV astrocytoma (glioblastoma multiforme [GBM])
                  including gliosarcoma

          -  Stratum 2 (USA patients only):

               -  Currently on stable dose of an enzyme-inducing anticonvulsant (with confirmed
                  therapeutic serum levels) for at least 2 weeks prior to study registration
                  including any of the following:

                    -  Phenytoin

                    -  Carbamazepine

                    -  Phenobarbital

               -  Histologically confirmed grade IV astrocytoma (GBM), gliosarcoma, grade III
                  astrocytoma, oligodendroglioma, or mixed oligoastrocytoma

          -  All patients must have unequivocal evidence of tumor progression by MRI or CT scan
             performed no longer than 14 days prior to study registration

               -  Patients undergoing surgery for progressive disease with nonmeasurable disease on
                  post-operative MRI, ideally obtained within 48 hours of surgery, (i.e.,
                  macroscopic gross total resection) are eligible

          -  ECOG performance status 0-2 (Karnofsky ≥ 60%)

          -  Life expectancy > 3 months

          -  Leukocytes ≥ 3,000/μL

          -  Absolute neutrophil count ≥ 1,500/μL

          -  Platelet count ≥ 100,000/μL

          -  Hemoglobin ≥ 9 g/dL

          -  Serum calcium ≤ 12.0 mg/dL

          -  Total bilirubin within normal institutional limits (ULN)

          -  AST(SGOT)/ALT(SGPT) ≤ 2.5 X institutional ULN

          -  Creatinine < 1.5 X institutional ULN

          -  Patients must have QTc < 500 msec

          -  The following groups of patients are eligible provided they have New York Heart
             Association class II cardiac function on baseline ECHO or MUGA:

               -  Those with a history of class II heart failure who are asymptomatic on treatment

               -  Those with prior anthracycline exposure

               -  Those who have received central thoracic radiation that included the heart in the
                  radiotherapy port

          -  Women of childbearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control or abstinence) prior to study entry and
             for the duration of study participation

               -  All women of childbearing potential must have a negative pregnancy test prior to
                  receiving sunitinib malate

          -  Patients with a history of QTc prolongation (defined as a QTc interval >= 500 msec),
             serious ventricular arrhythmia (VT or VF > 3 beats in a row) or other significant ECG
             abnormalities are excluded

          -  Patients with poorly controlled hypertension (systolic BP ≥ 140 mm Hg or diastolic BP
             ≥ 90 mm Hg) are ineligible

          -  Patients with any condition (e.g., gastrointestinal tract disease resulting in an
             inability to take oral medication or a requirement for IV alimentation, prior surgical
             procedures affecting absorption, or active peptic ulcer disease) that impairs their
             ability to swallow and retain sunitinib malate tablets are excluded

          -  Patients with any of the following conditions are excluded:

               -  Serious or non-healing wound, ulcer, or bone fracture

               -  History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
                  abscess within 28 days of treatment

               -  History of myocardial infarction, cardiac arrhythmia, stable or unstable angina,
                  symptomatic congestive heart failure, or coronary or peripheral artery bypass
                  graft or stenting within 12 months prior to study entry

               -  Class III or IV heart failure as defined by the NYHA functional classification
                  system

          -  Patients with a pre-existing thyroid abnormality who are unable to maintain thyroid
             function in the normal range with medication are ineligible

          -  Patients with uncontrolled intercurrent illness including, but not limited to, ongoing
             or active infections requiring antibiotics or psychiatric illness/social situations
             that would limit compliance with study requirements are ineligible

          -  Pregnant women are excluded from this study

          -  Breastfeeding should be discontinued if the mother is treated with sunitinib malate

          -  Patients are eligible if they received up to 1 previous chemotherapy regimen

          -  ≥ 12 weeks must have elapsed from the completion of radiation therapy

          -  ≥ 4 weeks from previous non-nitrosoureas-based cytotoxic chemotherapy

          -  ≥ 6 weeks from any nitrosoureas

          -  ≥ 2 weeks from last cytostatic chemotherapy such as erlotinib hydrochloride or
             tamoxifen

          -  Patients who have undergone previous stereotactic radiosurgery, intratumoral
             chemotherapy, or brachytherapy are eligible if functional imaging (PET or SPECT scan,
             MR spectroscopy, or dynamic MRI) supports the diagnosis of recurrent tumor or
             recurrent disease is confirmed histologically

          -  Concurrent steroids allowed provided the patients is on a stable or decreasing dose
             for at least 7 days prior to baseline tumor assessment (MRI and/or CT scan)

          -  Patients who have received prior treatment with any other antiangiogenic agent (e.g.,
             bevacizumab, sorafenib, pazopanib, AZD2171, PTK787, or VEGF Trap) are ineligible

          -  Patients who require use of therapeutic doses of coumarin-derivative anticoagulants
             such as warfarin or enoxaparin are excluded, although warfarin doses of up to 2 mg
             daily are permitted for prophylaxis of thrombosis

               -  Low molecular weight heparin is permitted provided the patient's PT INR is < 1.5

          -  Use of agents with proarrhythmic potential (e.g., terfenadine, quinidine,
             procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone,
             indapamide, or flecainide) is not permitted during the study

          -  No other investigational or commercial agents or non-investigational therapy designed
             to treat the brain malignancy (i.e., radiation therapy, systemic or intratumoral
             chemotherapy, biological agents, immunotherapy, or hormonal therapy) is allowed during
             the study period

          -  HIV-positive patients on combination antiretroviral therapy are ineligible

        Exclusion Criteria:

          -  History of allergic reactions attributed to compounds of similar chemical or
             biological composition to sunitinib malate

          -  Patients who have had chemotherapy within 4 weeks (6 weeks for nitrosoureas or
             mitomycin C) or radiation therapy within 12 weeks prior to entering the study or those
             who have not recovered from adverse events due to agents administered more than 4
             weeks earlier

               -  At least 4 weeks must have elapsed since any major surgery