A Phase II Study of the Combination of Aflibercept (VEGF-Trap) Plus Modified FOLFOX 6 in Patients With Previously Untreated Metastatic Colorectal Cancer

Inclusion Criteria:

- Histologically confirmed adenocarcinoma of colorectal origin that is metastatic or
locally advanced and unresectable

- Measurable disease, as defined by RECIST 1.1 criteria: one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded) as >=
10 mm with spiral computed tomography (CT) scan (CT scan slice thickness no greater
than 5 mm) malignant lymph nodes will be considered measurable if they are >= 15 mm
in short axis

- Must not have received any prior systemic therapy for metastatic or locally advanced
CRC; prior VEGF inhibitors are not allowed

- Prior adjuvant therapy for CRC including fluoropyrimidines either alone or in
combination with oxaliplatin is allowed, provided that all therapy was completed >=
12 months from cancer recurrence, therapy duration was =< 6 months, and all prior
toxicities have completely resolved (residual grade 1 neuropathy is allowed)

- Life expectancy >= 12 weeks

- Eastern Cooperative Oncology Group (ECOG) performance status 0-1

- Hemoglobin >= 9 g/dL (blood transfusion permitted to attain this value)

- Absolute neutrophil count >= 1,500/uL

- Platelets >= 100,000/uL

- Total bilirubin =< 2 x institutional upper limit of normal (ULN)

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT])
=< 2.5 x institutional ULN (may be =< 5x ULN if increase is due to metastatic
disease)

- Creatinine =< 1.5 x institutional ULN or creatinine clearance >= 60 mL/min/1.73 m2
for patients with creatinine levels above institutional U

- Urine protein:creatinine ratio (UPCR) < 1 or < 500 mg protein/24 hr

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- May not be receiving any other investigational agents

- Patients who have received any prior locoregional therapy for metastatic disease
(e.g. radiofrequency/microwave ablation, Yttrium-90 radioembolization, transarterial
chemoembolization, or surgical resection) are excluded

- Patients with known or suspected brain metastases, carcinomatous meningitis,
uncontrolled seizure disorder, active intracranial bleeding or active neurologic
disorder are excluded

- Patients with an active second primary malignancy or history of malignancy within the
5 years of enrollment are excluded, with the exception of non-melanoma skin cancers
and cervical cancer which has been treated with curative therapy

- Grade >= 2 sensory neuropathy at the time of enrollment

- Major surgery within 4 weeks of study start date; the surgical incision should be
fully healed prior to initiation of aflibercept

- Female or male patients of reproductive capacity unwilling to use methods appropriate
to prevent pregnancy are excluded; effective contraception is required for at least 3
months following the last administration of aflibercept

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, uncontrolled hypertension (blood pressure [BP] must be well controlled <
160/90), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social
situations that would limit compliance with study requirements, or any condition that
the principal investigator (PI) feels would make the patient ineligible

- Positive pregnancy screening test with a minimum sensitivity of 25 IU/L of human
chorionic gonadotropin (hCG) within 72 hours of registration; breastfeeding women are
also excluded

- History of pulmonary embolus within 3 months or deep venous thrombosis (DVT) within 4
weeks of enrollment; patients on anticoagulation must be on a stable dose of warfarin
with a therapeutic-range international normalized ratio (INR) or on a stable dose of
low molecular weight heparin

- Active congestive heart failure (New York Heart Association [NYHA] class II-IV)

- History of an arterial thrombotic vascular event including cerebrovascular accident
(CVA), myocardial infarction (MI), unstable angina, coronary or peripheral arterial
bypass graft, or transient ischemic attack (TIA) within 6 months

- Serious or non-healing wound, ulcer or bone fracture at the time of medication
administration

- History of treatment-resistant peptic ulcer disease, erosive esophagitis, gastritis,
or diverticulitis within 3 months

- History of gastrointestinal (GI) perforation within 5 years; current or prior
intestinal fistulas are also excluded

- Known chronic infectious disease including human immunodeficiency virus
(HIV)/acquired immune deficiency syndrome (AIDS)

- History of major hemorrhage including gastrointestinal bleeding (grade 2-4),
pulmonary hemorrhage, or clinically significant hemoptysis (> 1 tsp in 24 hours)
within the last 5 years; patients with underling conditions that predispose to
bleeding, such as bleeding diathesis, known esophageal varices, or tumor involving
major vessels, are also excluded

- Inability to understand or comply with study protocol

- Known hypersensitivity to Chinese hamster ovary cell products or to recombinant human
or murine antibodies, or any of the treatments in this protocol