Inclusion Criteria:

- Histological or cytological diagnosis of non-squamous, non-small cell lung cancer.

- Stage IV disease.

- Age > 18

- If female and of childbearing potential, documentation of negative pregnancy test
within 7 days prior to first dose.

- Sexually active women of childbearing potential must agree to use adequate
contraceptive measures, while on study and for 30 days after the last dose of study
drug. All fertile female subjects (and their partners) must agree to use a highly
effective method of contraception. Effective birth control includes (a) intrauterine
device (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).

- Able to provide informed consent and have signed an approved consent form that
conforms to federal and institutional guidelines.

Additional Phase II

Inclusion Criteria:

-No prior treatment for metastatic disease (Phase II ONLY). Patients who received
adjuvant systemic chemotherapy are eligible if greater than 6 months has elapsed.

Prior erlotinib treatment is allowed in phase I.

- Performance status of 0-1.

- One disease site meeting RECIST (version 1.1) criteria for measurable or
non-measurable disease. Disease sites measured from the CT portion of a combined
PET/CT may be used to document measurable disease (Liver or PET findings may be used
only for non-measurable disease).

Exclusion Criteria:

- Significant cardiovascular disease, including:

- Active, clinically symptomatic left ventricular failure.

- Uncontrolled hypertension: Systolic blood pressure of >140 mmHg or diastolic
blood pressure of >90 mmHg on 2 or more antihypertensive medications, documented
on 2 consecutive measurements taken at least 24 hours apart.

- Myocardial infarction, severe angina, or unstable angina within 6 months prior
to administration of first dose of study drug.

- History of serious ventricular arrhythmia (i.e., ventricular tachycardia or
ventricular fibrillation)

- Cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial
fibrillation that is well controlled with anti-arrhythmic medication)

- Coronary or peripheral artery bypass graft within 6 months of screening.

- Uncontrolled CNS metastases are not allowed; subjects with previously treated brain
metastases will be allowed if the brain metastases have been treated, toxicity of
radiation has resolved and steroids are no longer required. Leptomeningeal metastases
are not allowed.

- Any of the following hematologic abnormalities:

- Hemoglobin < 9.0 g/dL

- Absolute neutrophil count (ANC) < 1500 per mm3

- Platelet count < 100,000 per mm3

- INR >1.5 or PTT >1.5 × ULN

- 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)

- Creatinine > 2.0 × ULN

- Proteinuria > 3+ by urinalysis or urine dipstick

- 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; history of abdominal
fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks
prior to administration of first dose of study drug.

- Serious/active infection or infection requiring parenteral antibiotics.

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

- Significant thromboembolic or vascular disorders within 6 months prior to
administration of first dose of study drug, including but not limited to:

- Cerebrovascular accident (CVA) or transient ischemic attack (TIA)

- Peripheral arterial ischemia > Grade 2 (per CTCAE Version 4.0)

- Significant bleeding disorders within 6 months prior to administration of first dose
of study drug, including but not limited to:

- Hematemesis, hematochezia, melena or other gastrointestinal bleeding > Grade 2
(per CTCAE Version 4.0)

- Hemoptysis or other pulmonary bleeding (> 1/2 tsp/event over last 3 months not
associated with bronchoscopy)

- Hematuria or other genitourinary bleeding > Grade 2 (per CTCAE Version 4.0)

- Currently active second primary malignancy, including hematologic malignancies
(leukemia, lymphoma, multiple myeloma, etc.), other than non-melanoma skin cancers,
non-metastatic prostate cancer, in situ cervical cancer, and ductal or lobular
carcinoma in situ of the breast. Subjects are not considered to have a currently
active malignancy if they have completed anti-cancer therapy and have been disease
free for >2 years.

- Pregnant or lactating females.

- History of genetic or acquired immune suppression disease such as HIV; subjects on
immune suppressive therapy for organ transplant.

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

- Requirement for hemodialysis or peritoneal dialysis.

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

- Psychiatric disorder or altered mental status precluding informed consent or protocol
related testing.