primary rectal cancer without detectable distant metastasis, but with a high risk to relapse locally or systemically. MedDRA version: 12.1 Level: LLT Classification code 10038038 Term: Rectal cancer
Conditions
Interventions
Trade Name: Xeloda
Product Name: Xeloda
Pharmaceutical Form: Tablet
INN or Proposed INN: CAPECITABINE
CAS Number: 154361-50-9
Concentration unit: mg milligram(s)
Concentration type: equal
Concentratio
Sponsors
Dutch Colorectal Cancer Group
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Biopsy-proven, newly diagnosed primary rectal adenocarcinoma, i.e. with the lowest part of the tumour less than 16 cm from the anal verge using a rigid rectoscope or flexible endoscope . • Locally advanced tumour fulfilling at least one of the following criteria on pelvic MRI indicating high risk of failing locally and/or systemically: o Clinical stage (c) T4a, i.e. overgrowth to an adjacent organ or structure like the prostate, urinary bladder, uterus, sacrum, pelvic floor or side-wall (according to TNM version 5). o cT4b, i.e. peritoneal involvement. o Extramural vascular invasion (EMVI+). o N2, i.e. four or more lymph nodes in the mesorectum showing morphological signs on MRI indicating metastatic disease. Four or more nodes, whether enlarged or not, with a rounded, homogeneous appearance is thus not sufficient. o Positive MRF, i.e. tumor or lymph node one mm or less from the mesorectal fascia. o Enlarged lateral nodes, > 1 cm (lat LN+). • Staging done within 5 weeks before randomization. • No contraindications to chemotherapy, including adequate blood counts: - white blood count ?4.0 x 109/L - platelet count ?100 x 109/L - clinically acceptable haemoglobin levels - creatinine levels indicating renal clearance of ?50 ml/min - bilirubin ?35 µmol/l. • ECOG performance score ? 1, see appendix B. • Patient is considered to be mentally and physically fit for chemotherapy as judged by the oncologist. • Age ? 18 years • Written informed consent. • Adequate potential for follow-up. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Extensive growth into cranial part of the sacrum (above S3) or the lumbosacral nerve roots indicating that surgery will never be possible even if substantial tumour down-sizing is seen. • Presence of metastatic disease or recurrent rectal tumour. Familial Adenomatosis Polyposis coli (FAP), Hereditary Non-Polyposis Colorectal Cancer (HNPCC), active Crohn’s disease or active ulcerative Colitis. • Concomitant malignancies, except for adequately treated basocellular carcinoma of the skin or in situ carcinoma of the cervix uteri. Subjects with prior malignancies must be disease-free for at least 5 years. • Known DPD deficiency. • Any contraindications to MRI (e.g. patients with pacemakers). • Medical or psychiatric conditions that compromise the patient’s ability to give informed consent. • Concurrent uncontrolled medical conditions. • Any investigational treatment for rectal cancer within the past month. • Pregnancy or breast feeding. • Patients with known malabsorption syndromes or a lack of physical integrity of the upper gastrointestinal tract. • Clinically significant (i.e. active) cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac dysrhythmia, e.g. atrial fibrillation, even if controlled with medication) or myocardial infarction within the past 12 months. • Patients with symptoms or history of peripheral neuropathy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To increase the disease-free survival after 3 years follow-up;Secondary Objective: • To describe the toxicity profile of the combined modality treatment in schedule. • To determine the completion rate of the neo-adjuvant treatment. • To determine the fraction of patients with a radical resection (negative CRM) • To determine the pathological complete response rate (pCR). • To determine the postoperative complications • To describe the local recurrence rate after 3 years follow-up. • To evaluate quality of life. • To evaluate functional outcome. • To increase overall survival after 5 years of follow-up. ;Primary end point(s): 3-year disease-free survival | — |
Countries
Netherlands, Slovenia, Spain, Sweden
Outcome results
None listed