Preventive Treatment of OxaLiplatin Induced peripherAl neuRopathy in Adjuvant Colorectal Cancer

Inclusion Criteria:

1. Signed informed consent form before any study related assessments and willing tofollow all study procedures.
2. Male or female aged ≥18 years.
3. Pathologically confirmed adenocarcinoma of the colon or rectum including: Stage IIIcarcinoma (any T N1,2 M0) or Stage II carcinoma (T3,4 N0 M0).
4. The patient has undergone curative (R0) surgical resection performed within 12 weeksprior to randomization
5. The patient has a postsurgical carcinoembryonic antigen (CEA) level ≤1.5 x upper limitof normal (ULN, in current smokers, CEA level ≤2.0 x ULN is allowed).
6. No prior anti-cancer therapy for CRC except radiotherapy or concomitantchemo-radiotherapy using a fluoropyrimidine alone for locoregional rectal cancer.
7. Patient indicated for up to 6 months of oxaliplatin-based chemotherapy and withoutpathological findings of a neurologic exam performed prior to oxaliplatin treatmentaccording to local practice.
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
9. Adequate hematological parameters: hemoglobin ≥100 g/L, absolute neutrophil count ≥1.5x 109 /L, platelets ≥100 x 109 /L.
10. Adequate renal function: creatinine clearance >50 cc/min using the Cockcroft and Gaultformula or measured.
11. Adequate hepatic function: total bilirubin ≤1.5 x ULN (except in the case of knownGilbert's syndrome); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 x ULN.
12. Baseline blood manganese (Mn) level <2.0 x ULN.
13. For patients with a history of diabetes mellitus, HbA1c ≤7%.
14. Negative pregnancy test for women of child-bearing potential (WOCBP).
15. For men and WOCBP, use of adequate contraception (oral contraceptives, intrauterinedevice or surgically sterile) while on study drug and for at least 6 months aftercompletion of study therapy.

Exclusion Criteria:

1. Any evidence of metastatic disease.
2. Any unresolved toxicity by National Cancer Institute-Common Terminology Criteria forAdverse Events Version (NCI-CTCAE) v.4.03 >Grade 1 from previous anti-cancer therapy (including radiotherapy), except alopecia.
3. Any grade of neuropathy from any cause.
4. Any evidence of severe or uncontrolled systemic diseases (e.g., unstable oruncompensated respiratory, cardiac, unresolved bowel obstruction, hepatic or renaldisease).
5. Chronic infection or uncontrolled serious illness causing immunodeficiency. Patientswith known history of chronic hepatitis B can be enrolled if they are asymptomatic andan acute and active HBV infection can be excluded.
6. Any history of seizures.
7. A surgical incision that is not healed.
8. Known hypersensitivity to any of the components of mFOLFOX6 and, if applicable,therapies to be used in conjunction with the chemotherapy regimen or any of theexcipients of these products.
9. History of other malignancies (except for adequately treated basal or squamous cellcarcinoma or carcinoma in situ) within 5 years, unless the patient has been diseasefree for that other malignancy for at least 2 years.
10. Known dihydropyrimidine dehydrogenase deficiency.
11. Pre-existing neurodegenerative disease (e.g., Parkinson's, Alzheimer's, Huntington's)or neuromuscular disorder (e.g., multiple sclerosis, amyotrophic lateral sclerosis,polio, hereditary neuromuscular disease).
12. Major psychiatric disorder (major depression, psychosis), alcohol and/or drug abuse.
13. Patients with a history of second or third degree atrioventricular block or a familyheredity.
14. A history of a genetic or familial neuropathy.
15. Treatment with any investigational drug within 30 days prior to randomization.
16. Pregnancy, lactation or reluctance to using contraception.
17. Any other condition that, in the opinion of the Investigator, places the patient atundue risk.
18. Previous exposure to mangafodipir or calmangafodipir.
19. Welders, mine workers or other workers in occupations (current or past) where high Mnexposure is likely.