['rectal cancer']
['aflibercept', '5-fluoruracil', 'oxaliplatin', 'leucovorin']

        Inclusion Criteria:

          1. Signed and dated informed consent, and willing and able to comply with protocol
             requirement;

          2. Male or female subjects with rectal cancer ≥18 and <70 years of age;

          3. High risk MRI-defined operable rectal cancer (with an inferior margin no more than 12
             cm above the anal verge as assesed by MRI). Presence of at least 1 of the following on
             high resolution, thin-slice MRI (3 mm):

             Middle Third Tumors

               -  mrT3

                    1. Extramural vascular invasion (EMVI) positive

                    2. Extramural extension > 5 mms into perirectal fat

                    3. Mesorectal fascia (MRF) threatened or involved*

               -  mr T4***

             Distal Third Tumors (≤5 cm from anal verge)

               -  mrT3 tumor at or below levators

               -  T4 as above N2**

                    -  tumor or lymph node < 1 mm from the mesorectal fascia **≥4 lymph nodes in
                       the mesorectum showing morphological signs on MRI indicating metastatic
                       disease. ≥4 nodes, whether enlarged or not, with a rounded, homogeneous
                       appearance is thus not sufficient.

                         -  T4a: overgrowth to an adjacent organ or structure or T4b: peritoneal
                            involvement.

          4. Histologically confirmed adenocarcinoma of the rectum. All other histological types
             are excluded;

          5. ECOG Performance Status of ≤1;

          6. Hematological status: neutrophils (ANC) ≥1.5x109/L; platelets ≥100x109/L; hemoglobin
             ≥9g/dL;

          7. Adequate renal function: serum creatinine level <1.5 x upper limit of normality (ULN);

          8. Adequate liver function: serum bilirubin ≤1.5 x ULN, alkaline phosphatase <5xULN,
             AST/ALT < 3 x ULN;

          9. Proteinuria <2+ (dipstick urinalysis) or ≤1g/24hour;

         10. Regular follow-up feasible;

         11. For female patients of childbearing potential, negative serum pregnancy test within 1
             week (7 days) prior to starting study treatment;

         12. Female patients must commit to using reliable and appropriate methods of contraception
             until at least three months after the end of study treatment (when applicable). Male
             patients with a partner of childbearing potential must agree to use contraception in
             addition to having their partner use another contraceptive method during the trial.

        Exclusion Criteria:

          1. Prior treatment with aflibercept;

          2. History or evidence upon physical examination of metastasis;

          3. Uncontrolled hypercalcemia;

          4. Pre-existing permanent neuropathy (NCI grade ≥2);

          5. Uncontrolled hypertension (defined as systolic blood pressure >150 mmHg and/or
             diastolic blood pressure >100 mmHg), or history of hypertensive crisis, or
             hypertensive encephalopathy;

          6. Concomitant protocol unplanned antitumor therapy (e.g. chemotherapy, molecular
             targeted therapy, immunotherapy);

          7. Treatment with any other investigational medicinal product within 28 days prior to
             study entry;

          8. Other concomitant or previous malignancy, except: i/ adequately treated in-situ
             carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin,
             iii/ cancer in complete remission for >5 years;

          9. Any other serious and uncontrolled non-malignant disease, major surgery or traumatic
             injury within the last 28 days;

         10. Pregnant or breastfeeding women;

         11. Patients with known allergy to any excipient to study drugs;

         12. History of myocardial infarction and/or stroke within 6 months prior to randomization;
             Previous history of stable angina, uncontrolled arrhythmia, and acute coronary
             syndrome even if controlled with medication or with myocardial infarction within the
             last 12 months.

         13. Bowel obstruction.
      