A Phase II Trial of Sutent (Sunitinib; SU011248) for Recurrent Anaplastic Astrocytoma and Glioblastoma
A Phase II Trial of Sutent (Sunitinib; SU011248) for Recurrent Anaplastic Astrocytoma and Glioblastoma
We are asked patients to take part in this study because they had recurrent (returned) (1st
 or 2nd) anaplastic astrocytoma (AA) or glioblastoma multiforme (GBM).

 The purposes of this study are:

 -  To see if Sutent has any change on the patient and their cancer.

 -  To see if Sutent will slow or stop the growth of their tumor.

 -  To measure the safety of Sutent. Sutent is Food and Drug Administration (FDA) approved
 to treat patients with a gastrointestinal stromal tumor after the disease worsened while
 taking another medicine called imatinib mesylate or when imatinib mesylate cannot be
 taken. Sutent is also FDA approved to treat patients with advanced renal cell carcinoma.
 At this time, it is not known whether Sutent will improve symptoms, or help patients
 with this disease live longer.
Trial patients received sunitinib 50 mg daily for 4 weeks without regard to meals, followed
 by a 2-week rest period. This 6-week regimen constituted 1 cycle. Patients were treated for
 up to 9 cycles [~ year) or until disease progression or death or if persistent toxicities
 occurred. Complete blood count with differential, complete metabolic profile, neurologic
 exam, and brain magnetic resonance imaging (MRI) with contrast were obtained after each
 cycle. Toxicity assessments were obtained after each cycle. Toxicity was graded according to
 National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version
 3.0.

 SCHEDULE OF EVENTS - PROTOCOL ACTIVITIES

 <14 Days Prior to Initial Study Treatment:

 -  Neurological/Oncological History

 -  Neurological Examination

 -  Height/Weight/Body Surface Area

 -  Performance Status

 -  Quality of Life (QOL) FACT-L

 -  Laboratory Studies; complete blood count (CBC), Differential, Platelets, prothrombin
 time/partial thromboplastin time (PT/PTT), international normalized ratio (INR), Serum
 Creatinine, blood urea nitrogen (BUN), alanine aminotransferase (ALT), aspartate
 aminotransferase (AST), lactate dehydrogenase (LDH), Total Bilirubin, alkaline
 phosphatase (AlkPHs), Pregnancy Test, electrocardiogram (EKG)

 -  Cranial MRI or CT with and without contrast

 -  Multiple uptake gated acquisition (MUGA) Scan

 Day 1, At the Beginning of Each Treatment Cycle:

 -  Adverse Event Assessment

 -  Laboratory Studies; CBC, Differential, Platelets

 Every Cycle, Days 42-45 (within 3 days of next scheduled Sutent treatment):

 -  Neurological/Oncological History

 -  Neurological Examination

 -  Height/Weight/Body Surface Area

 -  Performance Status

 -  QOL FACT-L

 -  Laboratory Studies; Serum Creatinine, BUN, ALT, AST, LDH, Total Bilirubin, AlkPHs

 -  Cranial MRI or CT with and without contrast

 -  Survival

 At Off Study:

 -  Performance Status

 -  Cranial MRI or CT with and without contrast

 -  Survival
Inclusion Criteria:

 -  Resolution of all acute toxic effects of prior chemotherapy or radiotherapy or
 surgical procedures to NCI CTCAE Version 3.0 grade ≤1.

 -  Adequate organ function as defined by the following criteria:

 -  Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase
 [SGOT]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase
 [SGPT]) ≤3 x local laboratory upper limit of normal (ULN), or AST and ALT ≤3 x
 ULN if liver function abnormalities are due to underlying malignancy

 -  Total serum bilirubin ≤1.5 x ULN

 -  Absolute neutrophil count (ANC) ≥1500/µL

 -  Platelets ≥100,000/µL

 -  Hemoglobin ≥9.0 g/dL

 -  Serum calcium ≤12.0 mg/dL

 -  Serum creatinine ≤1.5 x ULN

 -  Patients must have histologically or neuroradiographically recurrent anaplastic
 astrocytoma (AA) or glioblastoma (GBM). Must have had prior pathologic confirmation of
 primary tumor histology.

 -  Must be ≥ 18 years old.

 -  Must have a Karnofsky performance status (KPS) ≥ 60%

 -  Measurable disease per MacDonald criteria required using contrast enhanced cranial
 MRI.

 -  Life expectancy ≥ 12 weeks.

 -  Must sign and date an Institutional Review Board (IRB) approved informed consent
 stating that he or she is aware of the neoplastic nature of the disease. Must
 willingly provide written consent after being informed of procedure to be followed,
 the experimental nature of the therapy, alternatives, potential benefits, side
 effects, risks, and discomforts.

 -  Willing and able to comply with scheduled visits, treatment plan, laboratory tests and
 accessible for follow-up.

 -  Have undergone surgery documenting tumor histology though repeat surgery at time of
 tumor recurrence is not mandatory.

 -  Have received prior external beam radiotherapy.

 -  Patients may have received one or two prior salvage chemotherapy and may have received
 adjuvant chemotherapy following initial surgery.

 -  May not have received prior stereotactic radiotherapy.

 -  May have been treated with Gliadel at initial surgery only.

 Exclusion Criteria:

 -  Major surgery or radiation therapy within 4 weeks of starting study treatment.

 -  NCI CTCAE grade 3 hemorrhage within 4 weeks of starting study treatment.

 -  History of or known spinal cord compression or carcinomatous meningitis, or evidence
 of leptomeningeal disease on screening CT or MRI scan.

 -  Any of the following within 6 months prior to study drug administration: myocardial
 infarction, severe/unstable angina, coronary/peripheral artery bypass graft,
 symptomatic congestive heart failure, cerebrovascular accident or transient ischemic
 attack, or pulmonary embolism.

 -  Ongoing cardiac dysrhythmias of NCI CTCAE grade ≥2.

 -  Prolonged QTc interval on baseline EKG.

 -  Hypertension that cannot be controlled by medications (>150/100 mm Hg despite optimal
 medical therapy).

 -  Pre-existing thyroid abnormality with thyroid function that cannot be maintained in
 normal range with medication.

 -  Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome
 (AIDS)-related illness or other active infection.

 -  Concurrent treatment on another clinical trial. Supportive care trials or
 non-treatment trials, e.g. QOL, are allowed.

 -  Concomitant use of ketoconazole and other agents known to inhibit Cytochrome P450 3A4
 (CYP3A4).

 -  Concomitant use of theophylline and phenobarbital and/or other agents metabolized by
 the cytochrome P450 system.

 -  Ongoing treatment with therapeutic doses of Coumadin (low dose up to 2 mg po daily for
 thrombo-prophylaxis is allowed).

 -  Pregnancy or breastfeeding. Female subjects must be surgically sterile,
 postmenopausal, or must agree to use effective contraception during the period of
 therapy. Female subjects with reproductive potential must have a negative pregnancy
 test (serum or urine) prior to enrollment. Male subjects must be surgically sterile or
 must agree to use effective contraception during the period of therapy.

 -  Other severe acute or chronic medical or psychiatric condition or laboratory
 abnormality that may increase the risk associated with study participation or study
 drug administration, or may interfere with interpretation of study results, and in the
 judgment of investigator would make patient inappropriate for entry into this study.

 -  Patients having been treated with 3 or more salvage regimens.

 -  Patients with a second active malignancy or diagnosis of other cancer within 3 years
 of enrollment, except for surgically cured basal cell carcinoma, or in situ carcinoma
 of the cervix.

 -  Mentally incapacitated patients or psychiatric illness that would prevent them from
 giving informed consent.

 -  Poorly controlled diabetes, hepatitis infection, uncontrolled high blood pressure,
 unstable angina, symptomatic congestive heart failure, and myocardial infarction
 within previous 6 months, or serious uncontrolled cardiac arrhythmia.

 -  Known to be HIV positive or to have an AIDS-related illness.

 -  Patients with an active infection that is not adequately controlled with antibiotics.

 -  Patients with other severe concurrent disease, which, in the judgment of the
 investigator, would make the patient inappropriate for entry into this study.

 -  Known sensitivity to any of the products to be administered during treatment.

 -  Currently enrolled in another clinical trial or patients who have participated in a
 trial of an investigational device or drug within the last 30 days.