Preoperative Valproic Acid and Radiation Therapy for Rectal Cancer

Inclusion Criteria:

• Patients with histologically confirmed diagnosis of adenocarcinoma of rectum falling into one of the following categories: T2N0 located at \<2 cm from anal verge T2N1 or T3N0-N1, located at \>5 cm and \<12 cm from anal verge and infiltration of perirectal fat up to a distance of 1 mm from mesorectal fascia (MRF) evaluated by MRI.

* Age ≥18 and ≤ 70
* ECOG Performance Status ≤1
* Effective contraception for both male and female patients if the risk of conception exist
* Signed written informed consent

Exclusion Criteria:

* Any previous treatment for rectal cancer
* Previous pelvic radiotherapy
* Presence of metastatic disease
* Recurrent rectal tumor
* Patient with Familial Adenomatosis Polyposis (FAP) or Hereditary Non-Polyposis Colorectal Cancer (HNPCC)
* History of inflammatory bowel disease or active disease
* Any concurrent malignancy except for adequately treated basocellular carcinoma of the skin or in situ carcinoma of cervix uteri. Patients with a previous malignancy but without evidence of disease for 5 years will be allowed to enter the trial.
* Neutrophils \< 2000/mm3 or platelets \< 100.000/ mm3 or haemoglobin \<9 gr/dl.
* Creatinine levels indicating renal clearance of \<50 ml/min
* GOT and/or GPT \> 2.5 time the UNL and/or bilirubin \>1.5 time the upper-normal limits (UNL)
* Significant cardiovascular comorbidity (e.g. myocardial infarction, superior vena cava \[SVC\] syndrome, patients with an ejection fraction of \<50%) or presence of cardiac disease that in the opinion of the Investigator increases the risk of ventricular arrhythmia.
* History of arrhythmia (multifocal premature ventricular contractions \[PVCs\], bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) which is symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained ventricular tachycardia.
* Patients with long QT-syndrome or QTc interval duration \> 480 msec or concomitant medication with drugs prolonging QTc (see list in the appendix)
* Known dihydropyrimidine dehydrogenase (DPD) deficiency
* HIV positive patients
* Patients who cannot take oral medication, who require intravenous alimentation, have had prior surgical procedures affecting absorption, or have active peptic ulcer disease.
* Known or suspected hypersensitivity to any of the study drugs.
* Patient who have had prior treatment with an HDAC inhibitor and patients who have received compounds with HDAC inhibitor-like activity, such as valproic acid.
* Concurrent uncontrolled medical conditions that might contraindicate study drugs.
* Major surgical procedure, within 28 days prior to study treatment start.
* Pregnant or lactating women.
* Women of childbearing potential with either a positive or no pregnancy test at baseline (NB. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential.
* Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study.