Preoperative Valproic Acid and Radiation Therapy for Rectal Cancer (V-shoRT-R3)
Colorectal Cancer
About this trial
This is an interventional treatment trial for Colorectal Cancer focused on measuring rectal, low risk, moderate risk
Eligibility Criteria
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.
Sites / Locations
- Istituto Nazionale Tumori Fondazione G. PascaleRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Active Comparator
Active Comparator
Active Comparator
Active Comparator
SCRT
V-SCRT
C-SCRT
VC-SCRT
short course radiotherapy (SCRT) alone 25 Gy in 5 fractions over one week.
Valproic acid (V) + short course radiotherapy
capecitabine (C) + short course radiotherapy
valproic acid + capecitabine + short course radiotherapy