Adjuvant Aflibercept for Metastatic Colorectal Cancer (C261)

Inclusion Criteria:

• First-line treatment of metastatic colorectal cancer with 3 or more metastases
• At least 10 cycles of FOLFOX. (Patients unable to complete 10 cycles of oxaliplatin, such as due to neuropathy or hypersensitivity reaction, may complete 10 cycles of treatment with 5-FU/leucovorin or FOLFIRI)
• No prior bevacizumab.
• Resection or ablation of all metastatic sites that have not achieved complete response with chemotherapy. The sequence of surgery, ablation and chemotherapy may be according to standard institutional procedure.
• Patients achieving a complete response in a metastatic site by stereotactic body radiation are eligible if the site was not easily accessible by surgery or ablation and a complete response was achieved.
• No severe, uncontrolled concurrent illness that would interfere with protocol therapy.
• No CNS disease
• ECOG Performance Status 0-2
• No chemotherapy or radiation therapy within last 3 weeks
• For patients who had 3 months of chemo, then surgery, then 3 months of chemo, patients must be off chemotherapy for no more than 8 weeks prior to randomization. For patients who had all their chemo and then surgery, they must be no more than 8 weeks from surgery prior to randomization.
• No concurrent anticancer therapy.
• Absolute neutrophil count ≥ 1,500/uL, Hgb > 9.0 g/dl, platelet ≥ 100,000/uL.
• Total bilirubin ≤ 1.5x upper limit of normal (ULN), AST or ALT ≤ 5x ULN;
• Creatinine < 1.5 x ULN
• Life expectancy of at least 12 weeks.
• Age ≥ 18 years
• Women of childbearing potential must have a negative pregnancy test.
• Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter.
• Voluntary written informed consent.

Exclusion Criteria:

• Residual metastatic disease after resection, ablation and chemotherapy
• Clinically significant cardiac disease (e.g., uncontrolled hypertension [blood pressure of >160/90 mmHg on medication], history of myocardial infarction within 6 months,), New York Heart Association (NYHA) Class II or greater congestive heart failure within 6 months, unstable arrhythmia. Patients with an atrial arrhythmia must have this condition well controlled on stable medication. Patients with current or recent (within 6 months) unstable angina are also not eligible.
• Significant bleeding diathesis or coagulopathy
• History of cerebral aneurysms or cerebral arteriovenous malformations.
• Patients with recent (within 12 months) arterial thromboembolic events, including transient ischemic attack (TIA), cerebrovascular accident (CVA), or clinically significant peripheral artery disease should also be excluded.
• Patients with a history of a gastrointestinal fistula or perforation.
• Women who are breast-feeding.
• Patients who have undergone major surgery, chemotherapy, or radiotherapy within the last 3 weeks.
• Patients on concurrent anticancer therapy.