Radiation therapy plus capecitabine and oxaliplatin chemotherapy and bevacizumab anti-angiogenetic therapy in locally advanced rectal cancer

Completed

Conditions: ocally advanced rectal cancer
Cancer
Malignant neoplasm of rectum

Registration Number: ISRCTN50181543

Lead Sponsor: niversity Medical Centre Schleswig-Holstein (Universitätsklinikum Schleswig-Holstein) (Germany)

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: All

Target Recruitment: 68

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 <= 1
6. Adequate bone marrow, hepatic and renal function:
6.1. Haemoglobin >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) <3 x upper limit of normal (ULN)
6.3. Total bilirubin <= 2 mg/dL
6.4. Creatinine clearance >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

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)