Tivozanib for Recurrent Glioblastoma

If you are willing to participate in this study, you will be asked to undergo some screening
tests and procedures that confirm you are eligible. Many of these tests and procedures are
likely to be part of regular cancer care and may be done even if it turns out taht you do not
take part in the research study. If you have had some of these tests or procedures recently,
they may or may not have to be repeated. The screening process may include the following: a
medical history, mini-mental status exam, physical exam, performance status,
electrocardiogram, blood tests, urine test. If these tests show that you are eligible to
participate in the research study, you will begin the study treatment. If you do not meet the
eligibility criteria, you will not be able to participate in this research study.

If you take part in this research study, you will be given a study drug-dosing calendar for
each treatment cycle. Each treatment cycle lasts 28 days (4 weeks) during which time you will
be taking the study drug once daily for 3 weeks and then no study drug for the last week of
each cycle. The diary will also include special instructions for taking the study drug.

During all cycles you will have a physical exam and you will be asked questions about your
general health and specific questions about any problems that you might be having and any
medications you may be taking.

Standard contrast-enhanced (CE) MRI scans will be done prior to all odd-numbered study
cycles. Vascular MRI scans will be done prior to start of treatment, Day 1 of treatment and
prior to all even-numbered cycles. These studies will be done in the Charlestown Navy Yard.

We would like to keep track of your medical condition for up to 24 months after your last
dose of study treatment. We would like to do this by calling you on the telephone once a year
to see how you are doing. Keeping in touch with you and checking your condition every year
helps us look at the long-term effects of the research study.

Inclusion Criteria:

- Histologically confirmed glioblastoma that has progressed based on imaging or surgery

- Measurable disease

- No more than 3 prior chemotherapy regimens

- Must have recovered from toxicity of prior therapy. An interval of at least 3 months
must have elapsed since the completion of the most recent course of radiotherapy; at
least 3 weeks since last non-nitrosourea containing chemotherapy regimen or
molecularly targeted agent; at least 6 weeks since the completion of a nitrosourea
containing chemotherapy regimen

- Life expectancy of at least 12 weeks

- Able to tolerate MRIs

- Willing to use adequate, highly effective contraception measures while on study and
for at least 45 days after the last dose of study drug

Exclusion Criteria:

- Pregnant or breastfeeding

- Major surgical procedure or significant traumatic injury within 28 days of starting
therapy; or minor surgical procedure within 7 days

- Receiving other study agents

- Prior therapy with an anti-VEGF agent

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to tivozanib

- Receiving any medications or substances that are inhibitors or inducers of CYP450
enzymes

- Significant cardiovascular disease

- Non-healing wound, bone fracture or skin ulcer

- Active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis or other
gastrointestinal condition with increased risk of perforation; abdominal fistula,
gastrointestinal perforation or intra-abdominal abscess within 4 weeks prior to
administration of first dose of study drug

- Uncontrolled intercurrent illness

- Significant thromboembolic or vascular disorders within 6 months prior to
administration of first dose of study drug

- Significant bleeding disorders within 6 months prior to administration of first dose
of study drug

- Currently active second primary malignancy

- HIV positive and on combination antiretroviral therapy

- Inability to swallow capsules, malabsorption syndrome or gastrointestinal disease that
severely affects the absorption of study drugs, major resection of the stomach or
small bowel, or gastric bypass procedure