Inclusion Criteria:

- Histologically confirmed glioblastoma at some point in their disease course

- All patients must have received prior standard therapy including resection if
feasible, radiation and temozolomide

- May have received 3 or fewer chemotherapy or biotherapy systemic regimens. Gliadel
wafer therapy is not counted as a regimen. Patients may not have received any prior
anti-VEGF, anti-EGF therapy or mTOR inhibitors.

- Lab values as outlined in protocol

- Must have recovered from immediate post-operative period and must be maintained on
stable or decreasing corticosteroid regimen for at least 3 days prior to the start of
treatment

- Must have recovered from possible complications of prior chemotherapies and have a
period of 28-42 days since last treatment. Patients must be at least 4 weeks from a
non-nitrosourea chemotherapy or 6 weeks from a nitrosourea chemotherapy. Patients
must be at least 1 week from the use of non-cytotoxic therapies

- Must be at least 3 months from the completion of radiation or radiosurgery

- Must have documented progression of the disease on the MRI scan using Macdonald
criteria

- KPS 60 or greater

- Mini-Mental Status Examination (MMSE) Score > 15

- 18 years of age or older

- All female participants of childbearing potential must have a negative pregnancy test
prior to enrollment

Exclusion Criteria:

- Evidence of severe or uncontrolled systemic disease or any concurrent condition which
in the Investigator's opinion makes it undesirable for the patient to participate in
the trial or which would jeopardize compliance with the protocol

- Clinically significant cardiovascular event 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 which is symptomatic or requires treatment or asymptomatic
sustained ventricular tachycardia. Atrial fibrillation, controlled on medication is
NOT an exclusion

- Previous history of QTc prolongation as a result from other medication that required
discontinuation of that medication

- Congenital QTc 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 480 or greater msec on screening
ECG

- Any concomitant medication that may cause QTc prolongation, induce Torsades de
Pointes or induce CYP3A4 function

- Hypertension not controlled by medical therapy

- Currently active diarrhea that may affect the ability of the patient to absorb the
vandetanib. Specifically, patients with diarrhea of CTCAE v3.0 grade III or above
will be excluded

- Women who are currently pregnant or breast-feeding

- Previous or current malignancies of other histologies within the last 5 years, with
the exception of cervical carcinoma in situ and adequately treated basal cell or
squamous cell carcinoma of the skin

- Receipt of any investigational agents within 30 days prior to commencing study
treatment

- Any unresolved toxicity greater than CTC grade 1 from previous anti-cancer therapy

- Major surgery, including craniotomy for tumor resection, within 4 weeks or
incompletely healed surgical incision before starting study therapy. Stereotactic
biopsy of the tumor within 2 weeks of starting therapy

- Patients on enzyme-inducing anti-epileptic (EIAED) drug therapy

- Patients unable to undergo MRI evaluation prior to potential enrollment

- Patients who, in the opinion of the treating neuro-oncologist, have a significant
intratumoral or peritumoral hemorrhage evident on pre-therapy MRI

- Patients with a history of wound-healing disorders, advanced coronary disease, or
with a recent history (<1 year) of peptic ulcer disease

- Patients with serious and chronic liver function abnormalities and uncontrolled
hyperlipidemia

- Patients unable to be treated with medications for PCP prophylaxis

- Patients with documented allergy to sirolimus

- Patients who are severely immunosuppressed

- Current anticoagulation is NOT criteria for exclusion