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

ISRCTN ISRCTN50181543
DOI https://doi.org/10.1186/ISRCTN50181543
Secondary identifying numbers Final 01/12.11.07
Submission date
14/04/2008
Registration date
09/05/2008
Last edited
09/05/2008
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Jürgen Dunst
Scientific

Universitätsklinikum Schleswig-Holstein
Campus Lübeck
Ratzeburger Allee 160
Lübeck
23538
Germany

Study information

Study designOpen-label, single-arm, non-randomised, phase II study.
Primary study designInterventional
Secondary study designNon randomised controlled trial
Study setting(s)Not specified
Study typeNot Specified
Participant information sheet Not available in web format, please use the contact details below to request a patient information sheet.
Scientific titlePhase II trial: Pre-operative, long-term chemoradiation with capecitabine, oxaliplatin and bevacizumab in locally advanced rectal cancer
Study acronymBevXelOx-RT
Study objectivesEfficacy of neoadjuvant radio-chemotherapy will be improved by an additional angiogenesis-inhibiting therapy using the vascular endothelial growth factor (VEGF) antibody bevacizumab.
Ethics approval(s)Ethics Committee of the Medical Faculty, University of Lübeck. Date of approval: 26/02/2008
Health condition(s) or problem(s) studiedLocally advanced rectal cancer
InterventionAll 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 typeDrug
Pharmaceutical study type(s)
PhasePhase II
Drug / device / biological / vaccine name(s)Capecitabine, oxaliplatin, bevacizumab.
Primary outcome measureHistopathological complete remission rate at time of surgery (approximately 4 weeks following study treatment)
Secondary outcome measures1. 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 study start date01/05/2008
Completion date31/12/2009

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participants68
Key inclusion criteria1. 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
Key exclusion criteria1. 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)
Date of first enrolment01/05/2008
Date of final enrolment31/12/2009

Locations

Countries of recruitment

  • Germany

Study participating centre

Universitätsklinikum Schleswig-Holstein
Lübeck
23538
Germany

Sponsor information

University Medical Centre Schleswig-Holstein (Universitätsklinikum Schleswig-Holstein) (Germany)
Hospital/treatment centre

Campus Lübeck
Ratzeburger Allee 160
Lübeck
23538
Germany

http://www.uk-sh.de
ROR logo https://ror.org/01tvm6f46

Funders

Funder type

Hospital/treatment centre

University Medical Centre Schleswig-Holstein (Universitätsklinikum Schleswig-Holstein) (Germany)

No information available

Roche Pharma AG (Germany)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan
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