Aflibercept and FOLFOX6 Treatment for Previously Untreated Stage IV Colorectal Cancer

This is an interventional treatment trial for Mucinous Adenocarcinoma of the Colon focused on measuring colorectal cancer, rectal cancer, FOLFOX, Aflibercept Read More

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