OXALIPLATIN PLUS 5-FLUOROURACIL BASED-CHEMOTHERAPY INDUCTION FOLLOWED BY PREOPERATIVE CHEMORADIATION VERSUS PREOPERATIVE CHEMORADIATON ALONE IN ADVANCED RECTAL ADENOCARCINOMA: RANDOMIZED CONTROLLED PHASE II STUDY

INTERVENTION: Trade Name: Eloxatin Product Name: Eloxatin Pharmaceutical Form: Powder for solution for infusion INN or Proposed INN: OXALIPLATIN CAS Number: 61825943 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: not less then Concentration number: 0.2‐ CONDITION: advanced rectal adenocarcinoma ; MedDRA version: 9.1 Level: LLT Classification code 10038028 Term: Rectal adenocarcinoma stage III PRIMARY OUTCOME: Main Objective: To assess if chemotherapy before chemoradiation can increase tumor downstaging in rectal cancer Primary end point(s): The primary objective of the study is to compare the achievement of a pT0‐1 stage in each arm . The pT0‐1 stage will be assessed as a binary variable.; Assuming a rate of 20% pT0‐1 stage in the radiochemotherapy arm, we calculated that we would need a sample of 110 patients (55 in each arm) to ensure 80% statistical power of detecting an improvement of 25% pT0‐1 stage with a two‐sided significance level of 0.05.; Secondary end‐points are tumoral and nodal down staging, sphincter preservation.; Secondary Objective: Toxicity ; Disease free survival INCLUSION CRITERIA: Inclusion criteria ‐ histologically confirmed rectal adenocarcinoma, located 0‐15 cm from the anal margin, T2‐4 / N+ amenable to indication for chemoradiotherapy. ‐ patients with resectable liver or pulmonary metastases (=3) could be included in this protocol ,providing that chemoradiation is indicated in the treatment plan. ‐ age > 18 ‐ WHO performance status (PS) of 0‐2 at study entry ‐ measurable (bi‐dimensionally with both diameters =1cm) / evaluable disease ‐ adequate renal (serum creatinin <1.5x upper reference range), liver (total bilirubin < 1.5x upper reference range) and hematopoietic function (PMN>1,5x 109/L, platelet >100x109/L), PTT = 1,5 upper reference range. ‐ life expectancy of at least 12 weeks ‐ effective contraception throughout the study for both male and female patients if the risk of conception exist. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 y