Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
Final 01/12.11.07
Study information
Scientific title
Phase II trial: Pre-operative, long-term chemoradiation with capecitabine, oxaliplatin and bevacizumab in locally advanced rectal cancer
Acronym
BevXelOx-RT
Study hypothesis
Efficacy of neoadjuvant radio-chemotherapy will be improved by an additional angiogenesis-inhibiting therapy using the vascular endothelial growth factor (VEGF) antibody bevacizumab.
Ethics approval
Ethics Committee of the Medical Faculty, University of Lübeck. Date of approval: 26/02/2008
Study design
Open-label, single-arm, non-randomised, phase II study.
Primary study design
Interventional
Secondary study design
Non randomised controlled trial
Trial setting
Not specified
Trial type
Not Specified
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet.
Condition
Locally advanced rectal cancer
Intervention
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 single doses) daily on days 1-14 and 22-35; 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.
Intervention type
Drug
Phase
Phase II
Drug names
Capecitabine, oxaliplatin, bevacizumab.
Primary outcome measure
Histopathological complete remission rate at time of surgery (approximately 4 weeks following study treatment)
Secondary outcome measures
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
Overall trial start date
01/05/2008
Overall trial end date
31/12/2009
Reason abandoned (if study stopped)
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
68
Participant 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 24hour 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)
Recruitment start date
01/05/2008
Recruitment end date
31/12/2009
Locations
Countries of recruitment
Germany
Trial participating centre
Universitätsklinikum Schleswig-Holstein
Lübeck
23538
Germany
Sponsor information
Organisation
University Medical Centre Schleswig-Holstein (Universitätsklinikum Schleswig-Holstein) (Germany)
Sponsor details
Campus Lübeck
Ratzeburger Allee 160
Lübeck
23538
Germany
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Hospital/treatment centre
Funder name
University Medical Centre Schleswig-Holstein (Universitätsklinikum Schleswig-Holstein) (Germany)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Roche Pharma AG (Germany)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list