Evaluating Trifluridine/Tipiracil Based Chemoradiation in Locally Advanced Rectal Cancer - The Phase I/II TARC Trial

Inclusion Criteria:

1. Male or female patients with histologically proven adenocarcinoma of the rectum (tumour ≤ 12 cm from the anal verge)
2. Indication for neoadjuvant chemoradiation: clinical tumour stage T3/4 or any node-positive disease (clinical stage according the TNM classification system, based on MRI).
3. No evidence of metastatic disease (as evidenced by negative CT-scan of the chest and abdomen).
4. The disease must be considered either resectable at the time of entry or expected to become resectable after preoperative chemoradiation.
5. Age ≥ 18 years
6. WHO/ECOG Performance Status ≤ 2
7. No prior cytotoxic chemotherapy or radiotherapy for rectal cancer.
8. No prior radiotherapy to the pelvis, for any reason.
9. Presence of adequate contraception in fertile patients. Adequate methods of contraception are: intra-uterine device, hormonal contraception, condom use with spermicide. Pregnant or breastfeeding women are excluded from participation.
10. Adequate bone marrow, hepatic and renal function: Haemoglobin ≥9.0 g/dL (transfusions allowed to achieve or maintain levels), absolute neutrophil count ≥ 1.5 x 109/L, platelet count ≥ 100 x 109/L, ALAT, ASAT ≤ 2.5 x ULN, Alkaline phosphatase ≤ 2.5 x ULN, Total bilirubin ≤1.5 x ULN, Creatinine clearance \> 50 mL/min (calculated according to Cockroft and Gault).
11. Ability to swallow tablets.
12. Written informed consent and patient's agreement to comply with the study protocol.

Exclusion Criteria:

1. Previous (within the last 3 years) or concurrent malignancies, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix or basal cell carcinoma of the skin.
2. Clinically significant (i.e. active) cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmia not well controlled with medication) or myocardial infarction within the last 12 months.
3. Known allergy or any other adverse reaction to any of the study drugs or to any related compound.
4. Known significant impairment of intestinal resorption (e.g. chronic diarrhea, inflammatory bowel disease).
5. Pre-existing condition which would deter chemoradiotherapy or radiotherapy, i.e. fistulas, severe ulcerative colitis (particularly patients currently taking sulphasalazine), Crohn's disease, prior adhesions.