Inclusion Criteria:

1. The subject must have participated on Protocol AV-951-09-301, and must meet either of
the following bulleted criteria:

Demonstrated disease progression per RECIST during treatment with sorafenib, OR

Demonstrated clinical benefit [complete response (CR), partial response (PR), or
stable disease (SD) per RECIST] and acceptable tolerability after treatment with
tivozanib or sorafenib on protocol AV-951-09-301

2. ECOG performance status ≤ 2 (see Appendix C) and life expectancy ≥ 3 months.

3. If female and of childbearing potential, documentation of negative pregnancy test
prior to enrollment.

4. Ability to give written informed consent

Exclusion Criteria:

1. Newly identified CNS malignancies or documented progression of CNS metastases;
subjects will be allowed only if the CNS metastases have been adequately treated with
radiotherapy or surgery. For subjects receiving steroid therapy please refer to
Section 6.3 for allowed steroid maintenance therapy

2. Duration since last dose on Protocol AV-951-09-301:

1. For subjects continuing tivozanib or sorafenib (subjects who demonstrated
clinical benefit and acceptable tolerability during treatment with tivozanib or
sorafenib on protocol AV-951-09-301): more than 2 weeks since last dose of
tivozanib or sorafenib

2. For subjects initiating tivozanib (ie demonstrated disease progression during
treatment with sorafenib): more than 4 weeks since last dose of sorafenib.
Subjects demonstrating disease progression due to CNS metastasis will be allowed
up to 8 weeks since last dose of sorafenib in order to complete treatment for
CNS metastasis

3. Inadequate recovery from any prior surgical procedure or major surgical procedure
within 4 weeks prior to administration of first dose of study drug

4. Any of the following hematologic abnormalities:

- Hemoglobin < 9.0 g/dL

- ANC < 1500 per mm3

- Platelet count < 75,000 per mm3

- PT or PTT >1.5 × ULN

5. Any of the following serum chemistry abnormalities:

- Total bilirubin > 1.5 × ULN (or > 2.5 × ULN for subjects with Gilbert's
syndrome)

- AST or ALT > 2.5 × ULN (or > 5 × ULN for subjects with liver metastasis)

- Alkaline phosphatase > 2.5 × ULN (or > 5 × ULN for subjects with liver or bone
metastasis)

- Creatinine > 2.0 × ULN

- Proteinuria > 3+ by urinalysis or urine dipstick

6. If female, pregnant or lactating

7. Sexually active pre-menopausal female subjects (and female partners of male subjects)
must use adequate contraceptive measures, while on study and for at least 50 days
after the last dose of study drug. Sexually active male subjects must use adequate
contraceptive measures, while on study and for at least 90 days after the last dose
of study drug. All fertile male and female subjects,and their partners,must agree to
use a highly effective method of contraception. Effective birth control includes (a)
IUD plus one barrier method; or (b) 2 barrier methods. Effective barrier methods are
male or female condoms, diaphragms, and spermicides (creams or gels that contain a
chemical to kill sperm). (Note: Oral, implantable, or injectable contraceptives may
be affected by cytochrome P450 interactions, and are not considered effective for
this study.)

8. Uncontrolled hypertension: systolic blood pressure > 150 mmHg or diastolic blood
pressure >100 mmHg on 2 or more antihypertensive medications, documented on 2
consecutive measurements taken at least 24 hours apart.

9. Unhealed wounds (including active peptic ulcers)

10. Serious/active infection or infection requiring parenteral antibiotics

11. Life-threatening illness or organ system dysfunction compromising safety evaluation

12. Psychiatric disorder, altered mental status precluding informed consent or necessary
testing

13. Inability to comply with protocol requirements

14. Treatment with another anti-cancer therapy or participation in another interventional
protocol (excluding AV-951-09-301)