A Trial of Single Agent Axitinib as Maintenance Therapy for Patients With First Line Metastatic Colorectal Cancer (mCRC)

All patients will receive FOLFOX/bevacizumab for four 28-day cycles (a total of 16 weeks).
After 4 cycles, maintenance axitinib will be started. With approval of the Medical
Monitor,patients who are having significant benefit from FOLFOX/bevacizumab may continue
chemotherapy to a maximum of six 28-day cycles. During trial treatment, all patients will be
assessed for response every 8 weeks (2 cycles).

Inclusion Criteria:

- Histologically or cytologically confirmed metastatic adenocarcinoma of the colon or
rectum.

- Patients must have measurable disease per RECIST Version 1.1.

- No previous systemic therapy for metastatic colorectal cancer. Previous
radiosensitizing chemotherapy is allowed, if completed at least 4 weeks prior to
Cycle 1 Day 1 of study treatment, and previous neoadjuvant and/or adjuvant
chemotherapy is allowed, if completed at least 6 months prior to diagnosis of
metastatic disease.

- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 to 1.

- Life expectancy >=12 weeks.

- Adequate hematologic, renal and hepatic function

- Patients who are on coumadin should have an INR value within the therapeutic range
(i.e., 2 to 3 x ULN). Patients who are on stable, chronic doses of coumadin are
eligible.

- Male patients willing to use adequate contraceptive measures. Female patients who are
not of child-bearing potential, and female patients of child-bearing potential who
agree to use adequate contraceptive measures, who are not breastfeeding, and who have
a negative serum or urine pregnancy test performed within 72 hours prior to start of
treatment.

- Willingness and ability to comply with the trial and follow-up procedures.

- Ability to understand the investigative nature of this trial and give written
informed consent.

Exclusion Criteria:

- History or known presence of central nervous system (CNS) metastases.

- Patients who have had a major surgical procedure (not including mediastinoscopy), or
significant traumatic injury <=4 weeks prior to beginning treatment.

- Women who are pregnant or lactating. All females of child-bearing potential must have
negative serum or urine pregnancy tests within 72 hours prior to study treatment (see
Appendix D)

- History of hypersensitivity to active or inactive excipients of any component of
treatment (5 fluorouracil, bevacizumab, oxaliplatin, or axitinib), or known
dipyrimidine dehydrogenase deficiency.

- Patients with proteinuria at screening as demonstrated by:

- Urine dipstick for proteinuria >=2+ (patients discovered to have >=2+
proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine
collection, and must demonstrate <=1 g of protein/24 hours to be eligible)

- Patients with a serious non healing wound, active ulcer, or untreated bone fracture.

- Patients with evidence of bleeding diathesis or significant coagulopathy (in the
absence of therapeutic anticoagulation).

- Patients with history of hematemesis or hemoptysis (defined as having bright red
blood of ½ teaspoon or more per episode) <=1 month prior to study enrollment.

- Patients requiring concomitant treatment with potent CYP3A4 or CYP1A2 inducers and
CYP3A4 inhibitors.

- History of myocardial infarction or unstable angina <=6 months prior to beginning
treatment.

- Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg
and/or diastolic blood pressure >100 mmHg while on antihypertensive medications).
Initiation of antihypertensive agents is permitted provided adequate control is
documented at least 1 week prior to Day 1 of study treatment.

- New York Heart Association Grade II or greater congestive heart failure.

- Serious cardiac arrhythmia requiring medication. Patients with chronic,
rate-controlled atrial fibrillation are eligible.

- Significant vascular disease (e.g., aortic aneurysm requiring surgical repair, or
recent peripheral arterial thrombosis) <=6 months prior to Day 1 of treatment.

- History of stroke or transient ischemic attack <=6 months prior to beginning
treatment.

- Any prior history of hypertensive crisis or hypertensive encephalopathy.

- History of abdominal fistula or gastrointestinal perforation <=6 months prior to Day
1 of beginning treatment.

- Concurrent severe, intercurrent illness including, but not limited to, ongoing or
active infection, or psychiatric illness/social situations that would limit
compliance with study requirements.

- Any known positive test for human immunodeficiency virus, hepatitis C virus or acute
or chronic hepatitis B infection.

- Mental condition that would prevent patient comprehension of the nature of, and risk
associated with, the study.

- Use of any non-approved or investigational agent <=28 days prior to administration of
the first dose of study drug. Patients may not receive any other investigational or
anti-cancer treatments while participating in this study.

- Past or current history of neoplasm other than the entry diagnosis with the exception
of treated non-melanoma skin cancer or carcinoma in situ of the cervix, or other
cancers cured by local therapy alone and a disease free survival >=5 years.

- Infection requiring IV antibiotics.

- Impairment of gastrointestinal function or gastrointestinal disease that may
significantly alter drug absorption (e.g. active inflammatory bowel disease,
uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or significant small
bowel resection).

- Inability to swallow whole tablets.

- Patients with > Grade 2 peripheral neuropathy.