Preoperative Valproic Acid and Radiation Therapy for Rectal Cancer
Phase 1
Recruiting
- Conditions
- Colorectal Cancer
- Interventions
- Registration Number
- NCT01898104
- Lead Sponsor
- National Cancer Institute, Naples
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 152
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description SCRT preoperative radiation therapy short course radiotherapy (SCRT) alone 25 Gy in 5 fractions over one week. V-SCRT preoperative radiation therapy Valproic acid (V) + short course radiotherapy C-SCRT preoperative radiation therapy capecitabine (C) + short course radiotherapy VC-SCRT preoperative radiation therapy valproic acid + capecitabine + short course radiotherapy C-SCRT Capecitabine capecitabine (C) + short course radiotherapy V-SCRT Valproic Acid Valproic acid (V) + short course radiotherapy VC-SCRT Valproic Acid valproic acid + capecitabine + short course radiotherapy VC-SCRT Capecitabine valproic acid + capecitabine + short course radiotherapy
- Primary Outcome Measures
Name Time Method number of patients with complete pathological tumor regression 8 weeks evaluated at definitive surgery, planned 8 weeks after the end of radiotherapy, in all the study arms of Phase 2
maximum tolerated dose of capecitabine, given alone or in combination with valproic acid up to 3 weeks Phase 1 primary objective
- Secondary Outcome Measures
Name Time Method overall survival 1 year number of patients with pathologic complete response 2 months number of patients alive with disease progression one year changes in quality of life from baseline up to 3 months
Trial Locations
- Locations (1)
Istituto Nazionale Tumori Fondazione G. Pascale
🇮🇹Napoli, Italy