Preoperative Valproic Acid and Radiation Therapy for Rectal Cancer

• Register: ClinicalTrials.gov
• Last refreshed on: 3 April 2023
• Main ID: NCT01898104
• Date of registration: 02/07/2013
• Prospective Registration: No
• Primary sponsor: National Cancer Institute, Naples
• Public title: Preoperative Valproic Acid and Radiation Therapy for Rectal Cancer V-shoRT-R3
• Scientific title: Phase 1/2 Study of Valproic Acid and Short-course Radiotherapy Plus Capecitabine as preoperatIve Treatment in Low-moderate Risk Rectal Cancer
• Date of first enrolment: May 2012
• Target sample size: 152
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/show/NCT01898104
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

Italy

Contacts

• Name: Antonio Avallone, M.D.

• Name: Antonio Avallone, M.D.
• Affiliation: National Cancer Institute, Naples

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: 70 Years
Gender: All

Health Condition(s) or Problem(s) studied

Colorectal Cancer

Intervention(s)

Drug: Capecitabine

Drug: Valproic Acid

Radiation: preoperative radiation therapy

Primary Outcome(s)

number of patients with complete pathological tumor regression [Time Frame: 8 weeks]

maximum tolerated dose of capecitabine, given alone or in combination with valproic acid [Time Frame: up to 3 weeks]

Secondary Outcome(s)

overall survival [Time Frame: 1 year]

changes in quality of life from baseline [Time Frame: up to 3 months]

number of patients with pathologic complete response [Time Frame: 2 months]

number of patients alive with disease progression [Time Frame: one year]

Secondary ID(s)

V-shoRT-R3

2012-002831-28

Source(s) of Monetary Support

Please refer to primary and secondary sponsors