Rectal Cancer And Pre-operative Induction Therapy Followed by Dedicated Operation. The RAPIDO Trial

Inclusion Criteria: Primary tumour characteristics:

1. Histological proof of newly diagnosed primary adenocarcinoma of the rectum
2. Locally advanced tumour fulfilling at least one of the following criteria on pelvicMRI indicating high risk of failing locally and/or systemically (T4a, i.e. overgrowthto an adjacent organ or structure like the prostate, urinary bladder, uterus, sacrum,pelvic floor or side wall (according to TNM version 5), cT4b, i.e. peritonealinvolvement, extramural vascular invasion (EMVI+). N2, i.e. four or more lymph nodesin the mesorectum showing morphological signs on MRI indicating metastatic disease.Positive MRF, i.e. tumor or lymph node < 1 mm from the mesorectal fascia. Enlargedlateral nodes, > 1 cm (lat LN+)

Exclusion Criteria:

1. Extensive growth into cranial part of the sacrum (above S3) or the lumbosacral nerveroots indicating that surgery will never be possible even if substantial tumourdown-sizing is seen
2. Presence of metastatic disease or recurrent rectal tumour
3. Familial Adenomatosis Polyposis coli (FAP), Hereditary Non-Polyposis Colorectal Cancer (HNPCC), active Crohn¡¦s disease or active ulcerative Colitis
4. Concomitant malignancies, except for adequately treated basocellular carcinoma of theskin or in situ carcinoma of the cervix uteri. Subjects with prior malignancies mustbe disease-free for at least 5 years
5. Known DPD deficiency
6. Any contraindications to MRI (e.g. patients with pacemakers)
7. Medical or psychiatric conditions that compromise the patient's ability to giveinformed consent
8. Concurrent uncontrolled medical conditions
9. Any investigational treatment for rectal cancer within the past month
10. Pregnancy or breast feeding
11. Patients with known malabsorption syndromes or a lack of physical integrity of theupper gastrointestinal tract
12. Clinically significant (i.e. active) cardiac disease (e.g. congestive heart failure,symptomatic coronary artery disease and cardiac dysrhythmia, e.g. atrial fibrillation,even if controlled with medication) or myocardial infarction within the past 12 months
13. Patients with symptoms or history of peripheral neuropathy