Locally advanced rectal cancer Cancer Malignant neoplasm of rectum
Conditions
Interventions
All participants will receive the following (single-arm study):
1. Radiotherapy: 5 × weekly 1.8 Gy to a total dose of 50.4 Gy
2. Chemotherapy: Capecitabine 1,650 mg/sqm orally (p.o.), (divided in 2 s
oxaliplatin 50 mg/sqm intravenously (i.v.) on days 1, 8, 22, 29 over a 120-min infusion with 500 ml 5% glucose
bevacizumab 5 mg/kg i.v. as short time infusion (30-90 min) prior to oxaliplatin administration on days 1, 15, 29.
Sponsors
University Medical Centre Schleswig-Holstein (Universitätsklinikum Schleswig-Holstein) (Germany)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age >18 years, both males and females 2. Patients with histologically proven adenocarcinoma of the rectum, tumour = 16 cm from the anal verge, u T3-4 or uN+ or Mason III/IV, staging will must be done by endorectal ultrasound and magnetic resonance imaging (MRI) or by endorectal unltrasound and high resolution computed tomography, no evidence of metastatic disease 3. No prior treatment, except for ileostomy (if necessary due to ileus) 4. No fistulas near the tumour 5. Eastern Cooperative Oncology Group (ECOG) Performance Status 10.0 g/dL, leucocyte count > 3.5 x 109/L, absolute neutrophil count >1.5 x 109/L, platelet count >100 x 109/L 6.2. Alkaline phosphatase, alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT) 50 mL/min 6.5. Creatinine <= 1.5 x ULN 7. Patients must have understood the contents of the protocol and signed written informed consent
Exclusion criteria
Exclusion criteria: 1. No presence of adequate contraception in fertile patients 2. Pregnant or breastfeeding women 3. Previous or persistent alcohol or drug abuses 4. Prior radiotherapy or chemotherapy to the pelvis, for any reason 5. Treatment with any investigational drug, agent nor procedure, (i.e. did not participate in another trial) within 4 weeks before entry in this trial 6. Treatment with other anti-cancer agents 7. Patients not able or willing to comply with the protocol treatment and investigations 8. Patients with uncontrolled severe somatic or psychological diseases, e.g.: 8.1. Despite medication uncontrolled cardiac diseases, myocardial infarction within the last 6 months prior to enrolment 8.2. Neurological or psychiatric disorders including seizures and dementia 8.3. Active, uncontrolled infection and sepsis 9. Symptomatic peripheral neuropathy >= grade 2 (National Cancer Institute - Common Terminology Criteria for Adverse Events [NCI CTCAE]) 10. Concurrent malignancies, with the exception of successfully treated cone-biopsied in situ carcinoma of the cervix or basal cell carcinoma of the skin 11. Chronic diarrhoea > grade 1 (NCI CTCAE) 12. Chronic inflammatory bowel disease or other pre-existing condition which would deter resorption of drugs (e.g. dumping syndrome, evidence of accelerated small bowel passage, evidence of deterred resorption due to gastric or bowel surgery) 13. Known hypersensitivity to platinum-containing drugs 14. Concurrent use of the antiviral agent sorivudine or chemically related analogues 15. Known dihydropyrimidine dehydrogenase deficiency 16. Known allergy to any of the study drugs or its ingredients 17. Interstitial pneumonia or extensive, symptomatic lung fibrosis 18. Organ allograft requiring immunosuppressive therapy 19. Severe, non-healing wounds, ulcers or fractures 20. Thrombosis or severe bleeding (except for bleeding of the tumour) within 6 months prior to enrolment 21. Bleeding diathesis or thrombophilia 22. Therapeutic anticoagulation (with marcumar or heparin) 23. Acetylsalicylic acid >325 mg per day or routine use of non-steroidal anti-inflammatory drugs which inhibit the function of platelets 24. Ascites nescessitating puncture 25. Patients with proteinuria >= 1+ at baseline, as long as a 24?hour urine collection demonstrates >500 mg of protein/ 24 hr 26. Concurrent treatment with St. John's wort 27. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the preoperative chemoradiation (exceptions: protective ileostomy and the planned resection of the rectal cancer)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Histopathological complete remission rate at time of surgery (approximately 4 weeks following study treatment) | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Pathological downstaging at time of surgery (approximately 4 weeks following study treatment) 2. Regression grading (according to Dvorak) at time of surgery (approximately 4 weeks following study treatment) 3. Sphincter preservation at time of surgery (approximately 4 weeks following study treatment) 4. Acute and subacute toxicity during study treatment, especially: 4.1. (Post)operative complications 4.2. Gastrointestinal perforation 4.3. Wound healing complications 4.4. Bleeding complications | — |
Countries
Germany
Outcome results
None listed