INCLUSION CRITERIA:
a) Patients with histologically proven intracranial malignant glioma will be eligible for this protocol. Malignant gliomas include glioblastoma multiforme (GBM), gliosarcoma (GS), anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic mixed oligoastrocytoma (AMO), or malignant astrocytoma NOS (not otherwise specified).
b) Patients may have received prior therapy with bevacizumab, but not within six weeks of starting treatment with sunitinib. Patients who received prior therapy with bevacizumab must have demonstrated radiographic disease progression while being treated with bevacizumab.
c) Patients must have progressed after radiation and temozolomide therapy and have an interval of greater than or equal to 4 weeks from the completion of radiation therapy to study entry. If the patient has had prior stereotactic radio surgery, true tumor progression must be corroborated by FDG-PET or MR spectroscopy imaging.
d) Patients must have evidence of tumor progression by contrast enhanced perfusion MRI or CT scan. This scan should be performed within 14 days prior to registration and on a five day-stable dose of steroids. If the steroid dose is increased between the date of imaging and registration, a new baseline MR/CT is required. The same type of scan (i.e., MRI or CT) must be used throughout the period of protocol treatment for tumor measurement.
e) Patients having undergone recent resection of recurrent or progressive tumor will be eligible as long as all of the following conditions apply:
-They have recovered from the effects of surgery.
-Residual disease following resection of recurrent tumor is not mandated for eligibility into the study. To best assess the extent of residual disease post-operatively, a CT/MRI should be done:
--no later than 96 hours in the immediate post-operative period, or
--at least 4 weeks post-operatively, and
--within 14 days of registration, and
--on a steroid dosage that has been stable for at least 5 days.
f) Normal organ and marrow function defined as: total leukocyte count greater than or equal to 3000 cells/ul, ANC greater than or equal to 1500 cells/ul, platelet count greater than or equal to 100,000 cells/ul, serum creatinine less than or equal to 2.0 times the upper limit of normal, and bilirubin less than or equal to 1.5 times the upper limit of normal, hemoglobin greater than or equal to 9.0 g/dL , serum calcium less than or equal to 12.0 mg/dL, AST/ALT less than or equal to 1.5 times the upper limit of normal, PT less than or equal to 1.5 ULN. Eligibility level for hemoglobin may be reached by transfusion.
g) The effects of sunitinib on the developing human fetus at the recommended therapeutic dose are unknown. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
h) All patients or their previously designated DPA (if the patient is deemed by the treating physician to be impaired or questionably impaired in such a way that the ability of the patient to give informed consent is questionable) must sign an informed consent indicating that they are aware of the investigational nature of this study.
i) Patients must be greater than or equal to 18 years old, and with a life expectancy greater than 8 weeks.
j) Patients must have a Karnofsky performance status of greater than or equal to 60.
k) Patients must have recovered from the toxic effects of prior therapy: 2 weeks from any investigational agent, two weeks from vincristine, 6 weeks from nitrosoureas, 3 weeks from procarbazine, 1 week for non-cytotoxic agents, (e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc.), and 4 weeks from other cytotoxic therapy. Any questions related to the definition of non-cytotoxic agents should be directed to the Study Chair.
l) Patients must not have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patients' ability to tolerate this therapy.
m) This study was designed to include women and minorities, but was not designed to measure differences of intervention effects. Males and females will be recruited with no preference to gender. No exclusion to this study will be based on race. Minorities will actively be recruited to participate.
EXCLUSION CRITERIA:
a) Patients who, in the view of the treating physician, have significant active cardiac, hepatic, renal, or psychiatric diseases are ineligible.
b) Patients with a history of prior therapy directed against VEGF (e.g. sorafenib, pazopanib, ZD6474, AZD2171), with the exception of bevacizumab, will not be allowed to enroll.
c) Concurrent use of other standard chemotherapeutics or investigative agents.
d) Patients known to have a malignancy (other than their malignant glioma) that has required treatment in the last 12 months and/or is expected to require treatment in the next 12 months (except non-melanoma skin cancer or carcinoma in-situ in the cervix).
e) Patients who have an active infection.
f) Pregnant (positive pregnancy test) or nursing women. Both fertile men and women must agree to use adequate contraceptive measures during study therapy and for at least 3 months after the completion of sunitinib therapy.
g) Concurrent anti-coagulation or anti-platelet medication (including aspirin, non-steroidal anti-inflammatory agents, COX-2 inhibitors).
h) Serious or non-healing wound, ulcer or bone fracture
i) History of any of the following within 6 months of study entry: abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, stroke, myocardial infarction or unstable angina. Patients will not undergo diagnostic screening for any of these conditions.
j) Invasive procedures defined as follows:
-Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day 1 therapy
-Anticipation of need for major surgical procedures during the course of the study
-Core biopsy within 7 days prior to start of therapy
k) Uncontrolled hypertension (greater than150/100 mmHg) while on antihypertensive medications.
l) New York Heart Association class II or greater congestive heart failure.
m) Serious cardiac arrhythmia requiring medication.
n) Evidence of bleeding diathesis, coagulopathy, or INR greater than 1.5.
o) History of allergic reactions attributed to compounds of similar chemical or biologic composition to sunitinib.
p) Patients receiving any enzyme inducing anti-epileptic drugs (EIAEDs) and other potent CYP3A4 modulators (per Appendixes B and C) within two weeks prior to treatment start are ineligible.
q) Baseline echocardiogram with ejection fraction less than 50% or greater than or equal to 20% decrease from a prior study
r) QTc interval greater than 500 msec on baseline EKG.
s) HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with sunitinib.
National Institutes of Health Clinical Center
Bethesda, Maryland 20892. Last update: 05/05/2009