Pre-Operative Treatment in REseCTable COlon CanceR

Inclusion Criteria

• •1. Patient's signed informed consent.
• •2. Patient's age ≥18 years at the time of signing the informed consent.
• •3. Histologically confirmed adenocarcinoma of the colon or upper rectum.
• •4. Confirmed mismatch-repair proficient and/or microsatellite stable tumor. Both Immunohistochemistry and PCR can be used for diagnosis.
• •5. Intent for curative surgery
• •6. Predicted T3 or T4 stage and or nodal positivity (N+) in a computed tomography and/or magnetic resonance imaging scan of the abdomen/pelvis as assessed by the local study team.
• •* T3-4 defined as invasion of surrounding tissue structures or organs
• •* N+ defined as regional lymph node(s) without fat hilus and short axis diameter of ≥1 cm
• •7. Absence of clear distant metastases assessed by the investigator based on respective routine evaluations within 6 weeks prior to inclusion into the trial (preferred: computed tomography of thorax and abdomen. Alternatively magnetic resonance images, sonography and x-rays might be used for assessment).
• •8. Absence of significant active wound healing including severe chronic non-healing wounds, ulcerous lesions or untreated bone fracture
• •9. ECOG performance status 0-2.
• •10. Adequate bone marrow, hepatic and renal organ function, defined by the following laboratory test results:
• •* Absolute neutrophil count ≥ 1.5 x 109/L (1,500/µL)
• •* Hemoglobin ≥ 80 g/L (8 g/dL) with or without transfusion
• •* Platelet count ≥ 100 x109/L (100,000/µL) without transfusion
• •* Total serum bilirubin of ≤ 1.5 x upper limit of normal (ULN)
• •* Aspartate aminotransferase (AST/GOT) ≤ 3.0 × ULN.
• •* Calculated glomerular filtration rate (GFR) according to Cockcroft-Gault formula or according to MDRD ≥ 50 mL/min or serum creatinine ≤ 1.5 x ULN
• •11. Patients without anticoagulation need to present with an INR \< 1.5 x ULN and PTT \< 1.5 x ULN. Patient with prophylactic or therapeutic anticoagulation are allowed into the trial.
• •12. Proficient fluorouracil metabolism as defined:
• •1. Prior treatment with 5-FU or capecitabine without unusal toxicity or
• •2. If tested, normal DPD deficiency test according to the standard of the study site or
• •3. If tested, in patients with DPD deficiency test with a CPIC activity score of 1.0-1.5 fluoropyrimidine dosage should be reduced by 50%
• •13. For women of childbearing potential (WOCBP): negative pregnancy test within 7 days before treatment initiation and agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods with a failure rate of \< 1% per year during the treatment period and for at least 6 months after the last dose of study treatment.
• •A woman is considered to be of childbearing potential if she is post-menarcheal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). Examples of contraceptive methods with a failure rate of \< 1% per year include bilateral tubal ligation, male partner's sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
• •For men: With female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of \< 1% per year during the treatment period and for 6 months after the last dose of study treatment. Men must refrain from donating sperm during this same period.
• •With pregnant female partners, men must remain abstinent or use a condom during the treatment period and for 6 months after the last dose of study medication to avoid exposing the embryo.