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Preoperative Valproic Acid and Radiation Therapy for Rectal Cancer

Information source: National Cancer Institute, Naples
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Colorectal Cancer

Intervention: preoperative radiation therapy (Radiation); Valproic Acid (Drug); Capecitabine (Drug)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: National Cancer Institute, Naples

Official(s) and/or principal investigator(s):
Antonio Avallone, M.D., Principal Investigator, Affiliation: National Cancer Institute, Naples

Overall contact:
Antonio Avallone, M.D., Phone: +39 081 5903629, Email: avalloneantonio@libero.it


The purpose of this study is to first determine the maximum tolerated dose of capecitabine given alone or in combination with valproic acid during preoperative short-course radiotherapy (Phase 1). The next part of the study (Phase 2)will explore whether the addition of valproic acid or the addition of capecitabine to short-course radiotherapy, before optimal radical surgery might increase the pathologic complete tumor regression rate in patients with low-moderate risk rectal cancer.

Clinical Details

Official title: Phase 1/2 Study of Valproic Acid and Short-course Radiotherapy Plus Capecitabine as preoperatIve Treatment in Low-moderate Risk Rectal Cancer

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

maximum tolerated dose of capecitabine, given alone or in combination with valproic acid

number of patients with complete pathological tumor regression

Secondary outcome:

overall survival

number of patients alive with disease progression

number of patients with pathologic complete response

changes in quality of life from baseline


Minimum age: 18 Years. Maximum age: 70 Years. Gender(s): Both.


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


- 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


- 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.

Locations and Contacts

Antonio Avallone, M.D., Phone: +39 081 5903629, Email: avalloneantonio@libero.it

Istituto Nazionale Tumori Fondazione G. Pascale, Napoli, Italy; Recruiting
Additional Information

Starting date: May 2012
Last updated: December 29, 2014

Page last updated: August 20, 2015

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