Inclusion Criteria

- INCLUSION CRITERIA:

Patients with histologically proven malignant primary gliomas who have progressive disease
after radiotherapy will be eligible for this protocol. These include glioblastoma
multiforme (GBM), gliosarcoma, anaplastic astrocytoma (AA), anaplastic oligodendroglioma
(AO), anaplastic mixed oligoastrocytoma (AMO), and malignant glioma/astrocytoma NOS.

Patients must have an MRI/CT scan performed within 14 days prior to registration and on a
fixed dose of steroids for at least 5 days. 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,
that is, MRI or CT must be used throughout the period of protocol treatment for tumor
measurement.

Patients having undergone recent resection of recurrent or progressive tumor will be
eligible as long as all of the following conditions apply:

Patients will be eligible four weeks after surgery if 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.

If the 96 hour scan is more than 14 days before registration, the scan needs to be
repeated. If the steroid dose is increased between the date of imaging and registration,
a new baseline MRI/CT is required on a stable steroid dosage for at least 5 days.

Patients must have failed prior radiation therapy.

All patients or their previously designated DPA (if the patient is deemed by the treating
physician to be cognitively 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.

Patients must be greater than or equal to 18 years old, and must have a life expectancy
greater than 8 weeks.

Patients must have a Karnofsky performance status of greater than or equal to 60.

Patients must be at least six weeks from radiation therapy. Additionally, patients must be
at least 6 weeks from nitrosoureas, 4 weeks from temozolomide, 3 weeks from procarbazine,
and 2 weeks from last vincristine administration. Patients must be at least 4 weeks from
other cytotoxic therapies not listed above and 2 weeks for non-cytotoxic agents (e.g.,
interferon, tamoxifen) including investigative agents.

Patients must have adequate bone marrow function (WBC greater than or equal to
3,000/microL, ANC greater than or equal to 1,500/mm(3), platelet count of greater than or
equal to 100,000/mm(3), and hemoglobin greater than or equal to 10 gm/dl), adequate liver
function (AST, ALT and alkaline phosphatase 2.5 less than or equal to ULN and bilirubin
less than or equal to 1.5 times ULN), and adequate renal function (creatinine less than or
equal to 1.5 mg/dL and/or creatinine clearance greater than or equal to 60 cc/min) before
starting therapy. Patients must also have serum potassium greater than or equal to 3.5
mg/dL, magnesium greater than or equal to 0.75 mmol/L and calcium levels within normal
levels; supplementation is allowed. In cases where the serum calcium is below the normal
range, 2 options would be available: 1) the calcium adjusted for albumin is to be
obtained and substituted for the measured serum value. Exclusion is to then be based on
the adjusted for albumin values falling below the normal limit. 2) Determine the ionized
calcium levels. Exclusion is then to be based if these ionized calcium levels are out of
normal range despite supplementation. These tests must be performed within 14 days prior
to registration. Eligibility level for hemoglobin may be reached by transfusion.

Patients must either not be receiving steroids, or be on a stable dose of steroids for at
least five days prior to registration.

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.

Patients must not be pregnant or nursing, and all patients (both men and women) must be
willing to practice birth control during and for 2 months after treatment with vandetanib
and/or carboplatin. Women of childbearing potential (WCBP) must have a negative serum or
urine pregnancy test. In addition, WCBP patients must agree to use adequate contraceptive
methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation;
intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner).

A 12 lead electrocardiogram (ECG) to be performed within 2 weeks of trial entry with QTc
less than 480 msec.

EXCLUSION CRITERIA:

Patients who, in the view of the treating physician, have significant active hepatic,
renal, or psychiatric diseases are ineligible.

Prior treatment with vandetanib.

Prior treatment with platinum-based therapy.

Patients known to have an allergic response to mannitol.

Clinically significant cardiovascular event (e.g. myocardial infarction, superior vena
cava syndrome (SVC), New York Heart Association (NYHA) classification of heart disease
greater than or equal to 2 within 3 months before entry; or presence of cardiac disease
that, in the opinion of the investigator, increases the risk of ventricular arrhythmia.

History of arrhythmia (multifocal premature ventricular contractions PVCs), bigeminy,
trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) which is
symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained ventricular
tachycardia. Atrial fibrillation, controlled on medication is not excluded.

QTc prolongation with other medications that required discontinuation of that medication.

Congenital long QT syndrome, or 1st degree relative with unexplained sudden death under 40
years of age.

Presence of left bundle branch block (LBBB.)

QTc with Bazett's correction that is unmeasurable, or greater than or equal to 480 msec on
screening ECG. (Note: If a subject has a QTc interval greater than or equal to 480 msec on
screening ECG, the screen ECG may be repeated twice (at least 24 hours apart). The
average QTc from the three screening ECGs must be less than 480 msec in order for the
subject to be eligible for the study. Patients who are receiving a drug that has a risk of
QTc prolongation excluded if QTc is greater than or equal to 460 msec.

Any concurrent medication that may cause QTc prolongation or induce Torsades de Pointes.
Drugs listed in Appendix E, Table 2, that in the investigator's opinion cannot be
discontinued are allowed; however, must be monitored closely.

Concomitant medications that are potent inducers (rifampicin, rifabutin, St. John's Wort
and EIAEDs of CYP3A4 function. EIAEDs are allowed.

Hypertension not controlled by medical therapy (systolic blood pressure greater than 160
mm Hg or diastolic blood pressure greater than 100 mm Hg)

Currently active diarrhea that may affect the ability of the patient to absorb the
vandetanib or tolerate diarrhea.

Women who are currently pregnant or breast feeding.

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 for non-melanoma skin cancer, carcinoma in situ in the cervix or ductal
carcinoma in situ).

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 D1 therapy

Patients should not be on anti-platelet medications (aspirin, clopidogrel, ticlopidine,
prasugel). Non-steroidal anti-inflammatory drugs should be used with caution if medically
necessary.