BrUOG C261:Single Agent Adjuvant Aflibercept for Patients With Resected or Ablated Metastatic Colorectal Cancer: A Randomized Phase II Study

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.