Capecitabine for Rectal cancer | Adenocarcinoma of the rectum

Inclusion criteria

• {"criterion_text":"- Patients with histologically confirmed diagnosis of adenocarcinoma of rectum falling into one of the following categories:"}
• {"criterion_text":"- T2N0 located at <2 cm from anal verge"}
• {"criterion_text":"- T2N1 or T3N0-N1, located at >5 cm and <12 cm from anal verge and infiltration of perirectal fat up to a minimum distance of1 mm from mesorectal fascia (MRF) evaluated by MRI."}
• {"criterion_text":"- Age ≥18 and ≤ 75"}
• {"criterion_text":"- ECOG Performance Status ≤1"}
• {"criterion_text":"- Effective contraception for both male and female patients if the risk of conception exist"}
• {"criterion_text":"- Signed written informed consent"}

Exclusion criteria

• {"criterion_text":"- Any previous treatment for rectal cancer"}
• {"criterion_text":"- Previous pelvic radiotherapy"}
• {"criterion_text":"- Presence of metastatic disease"}
• {"criterion_text":"- Recurrent rectal tumor"}
• {"criterion_text":"- Patient with Familial Adenomatosis Polyposis (FAP) or Hereditary Non-Polyposis Colorectal Cancer (HNPCC)"}
• {"criterion_text":"- History of inflammatory bowel disease or active disease"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Neutrophils < 2000/mm3 or platelets < 100.000/ mm3 or haemoglobin <9 gr/dl."}
• {"criterion_text":"- Creatinine levels indicating renal clearance of <50 ml/min"}
• {"criterion_text":"- GOT and/or GPT > 2.5 time the UNL and/or bilirubin >1.5 time the upper-normal limits (UNL)"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Patients with long QT-syndrome or QTc interval duration > 480 msec or concomitant medication with drugs prolonging QTc (see list in the appendix)"}
• {"criterion_text":"- Known dihydropyrimidine dehydrogenase (DPD) deficiency"}
• {"criterion_text":"- HIV positive patients"}
• {"criterion_text":"- Patients who cannot take oral medication, who require intravenous alimentation, have had prior surgical procedures affecting absorption, or have active peptic ulcer disease."}
• {"criterion_text":"- Known or suspected hypersensitivity to any of the study drugs."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Concurrent uncontrolled medical conditions that might contraindicate study drugs."}
• {"criterion_text":"- Major surgical procedure, within 28 days prior to study treatment start."}
• {"criterion_text":"- Pregnant or lactating women."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study"}

Primary endpoints

• {"endpoint_text":"- Fase 1 : MTD capecitabina MTD capecitabina + acido valproico Fase 2: tasso di TRG1","definition_or_measurement_approach":"Phase 1: to determine the MTD of Capecitabine given alone or in combination with valproic acid during preoperative short-course radiotherapy (SCRT). Phase 2: to explore whether the addition of valproic acid or capecitabine to short-course radiotherapy before surgery might increase the pathologic complete tumor regression (TRG1) rate."}

Secondary endpoints

• {"endpoint_text":"- Local control","definition_or_measurement_approach":"To compare local control within each planned phase 2 comparison."}
• {"endpoint_text":"- Disease free survival","definition_or_measurement_approach":"To compare disease-free survival within each planned phase 2 comparison."}
• {"endpoint_text":"- Overall survival","definition_or_measurement_approach":"To compare overall survival within each planned phase 2 comparison."}
• {"endpoint_text":"- Pathological CRM negative (margin >1 mm) and lymph node negative rate","definition_or_measurement_approach":"Pathological margin and nodal status assessed on surgical specimen; compared between arms within planned phase 2 comparisons."}
• {"endpoint_text":"- Short and long-term toxicity","definition_or_measurement_approach":"Toxicity assessed using standard CTCAE criteria and compared between arms."}
• {"endpoint_text":"- Surgical Complications","definition_or_measurement_approach":"Surgical complication rates recorded post-operatively and compared between arms."}
• {"endpoint_text":"- Quality of Life","definition_or_measurement_approach":"Quality of life measured by validated instruments (not further specified in provided extract) and compared between arms."}

Other endpoints

• {"endpoint_text":"- To validate the predictive role of early tumor metabolic changes measured by PET scan (both phase 1 and 2)","definition_or_measurement_approach":"Early tumor metabolic changes measured by PET scan; role evaluated as predictive biomarker in both phase 1 and phase 2."}
• {"endpoint_text":"- To explore diagnostic accuracy of pre-surgical rectal biopsy (both phase 1 and 2)","definition_or_measurement_approach":"Diagnostic accuracy of pre-surgical rectal biopsy compared to surgical pathology."}
• {"endpoint_text":"- Biomarker studies on tumor and blood samples.","definition_or_measurement_approach":"Exploratory biomarker studies on tumor tissue and blood samples; specific assays not described in provided extract."}

Italy

Earliest CTIS Part Ii Submission Date

13-05-2024

Latest Decision Or Authorization Date

24-11-2025

Processing Time Days

560

Number Of Sites

3

Number Of Participants

120

Primary sponsor

Full Name

IRCCS Istituto Nazionale Tumori Fondazione Pascale

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy