Primary rectal cancer with high risk of failing locally and/or systemically. Keywords: rectal cancer, neoadjuvant chemotherapy, short course radiotherapy
Conditions
Interventions
Patients will be randomized between an experimental group in which short course 5 x 5 Gy radiation scheme is followed by six cycles of combination chemotherapy (capecitabine and oxaliplatin) and surge
Sponsors
University Medical Center Groningen, PO BOX 3001 , 9700 RB , Groningen , The Netherlands
Eligibility
Inclusion criteria
Inclusion criteria: Primary tumour characteristics: 1. Histological proof of newly diagnosed primary adenocarcinoma of the rectum; 2. Locally advanced tumour fulfilling at least one of the following criteria on pelvic MRI indicating high risk of failing locally and/or systemically (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), cT4b, i.e. peritoneal involvement, extramural vascular invasion (EMVI+). 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. Positive MRF (previously named CRM), i.e. tumor or lymph node 1 cm (lat LN+).
Exclusion criteria
Exclusion criteria: 1. 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; 2. Presence of metastatic disease or recurrent rectal tumour; 3. Familial Adenomatosis Polyposis coli (FAP), Hereditary Non-Polyposis Colorectal Cancer (HNPCC), active Crohn's disease or active ulcerative Colitis; 4. 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; 5. Known DPD deficiency; 6. Any contraindications to MRI (e.g. patients with pacemakers); 7. Medical or psychiatric conditions that compromise the patient's ability to give informed consent; 8. Concurrent uncontrolled medical conditions; 9. Any investigational treatment for rectal cancer within the past month; 10. Pregnancy or breast feeding; 11. Patients with known malabsorption syndromes or a lack of physical integrity of the upper gastrointestinal tract; 12. 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; 13. Patients with symptoms or history of peripheral neuropathy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Disease related Treatment Failure (3-years after surgery) | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Overall survival; 2. CRM negative (margin > 1 mm) rate; 3. Pathological complete response (pCR) rate; 4. Short and long-term toxicity; 5. Surgical complications; 6. Quality of life. | — |
Contacts
Public ContactElma Meershoek - Klein Kranenbarg
Leiden University Medical center Dept. of Surgery, Clinical Research Center, K6-R P.O. Box 9600
Outcome results
None listed