Multicentre international study of capecitabine ± bevacizumab as adjuvant treatment of colorectal cancer

Conditions: Histologically proven stage III (stage T2, T3 or T4) and stage II (any one or more of the following – stage T4, lymphatic invasion, vascular invasion, peritoneal involvement, poor differentiation) colorectal cancer (expected ratio 70%:30%). N.B Patients can be Stage II, T3 as long as they have one of the other poor prognostic features. For the purposes of stratification, rectal cancers will be anything below the peritoneal reflection.
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2004-000629-32-AT

Lead Sponsor: niversity of Oxford

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 2240

Inclusion Criteria

1. Histologically proven stage III (stage T2, T3 or T4) and stage II (any one or more of the following – stage T4, lymphatic invasion, vascular invasion, peritoneal involvement, poor differentiation, obstruction and perforation of the primary tumor during the pre-operative period) colorectal cancer (expected ratio 70%:30%). N.B Patients can be Stage II, T3 as long as they have one of the other poor prognostic features. For the purposes of stratification, rectal cancers will be anything below the peritoneal reflection. For the purposes of randomisation/stratification rectosigmoid tumours (above the peritoneal reflection) will be categorised as colonic tumours. If you have any doubt about the staging or if the histology report is in the Dukes’
staging system refer to Appendix 15.
2. Patients must have undergone complete resection of the primary tumour without evidence of residual disease.
3. Patients must be randomised to start treatment a minimum of 28 days and maximum of 70 days after surgery. [If a subject has had a major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start, or there is the anticipated need for major surgical procedure during the course of the study they are not eligible].
4. WHO Performance Status 0 or 1.
5. Male or female outpatients age größer/gleich 18 years.
6. Written informed consent given.
7. Life expectancy of größer/gleich 5 years, in terms of non-cancer-related morbidity.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 2240
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2240

Exclusion Criteria

1. Previous chemotherapy, immunotherapy or infra-diaphragmatic radiotherapy; or patients who are expected to require radiotherapy to these sites within the next 12 months, for any reason.
2. Received any investigational drug or agent/procedure, (i.e. participation in another treatment trial) within 4 weeks of randomisation.
3. Moderate or severe renal impairment [creatinine clearance < 30ml/min (calculated according to Cockroft-Gault formula–see Appendix 4).
4. Any of the following laboratory values (tests must not have been carried out more than 2 weeks prior to randomisation):
a. Absolute neutrophil count (ANC) <1.5 x 109/L
b. Platelet count < 100 x 109/L
c. Total bilirubin > 1.5 ULN
d. ALT, AST > 2.5 x ULN
e. Alkaline phosphatase > 2.5 x ULN
(ULN = Upper Limit of Normal)
5. Patients requiring chronic use of full dose oral or parenteral anticoagulants, high dose aspirin (>325mg/day), anti-platelet drugs or known bleeding diathesis. Low dose aspirin is allowed.
6. Proteinuria > 500 mg/24 hours.
7. Known coagulopathy.
8. Clinically significant cardiovascular disease [i.e. active; or <12 months since e.g. cerebrovascular accident, myocardial infarction, unstable angina, New York Heart Association (NYHA) grade II (see Appendix 14) or greater congestive heart failure, serious cardiac arrhythmia requiring medication; or uncontrolled hypertension].
9. Concomitant treatment with sorivudine or its chemically related analogues such as brivudine.
10. Pregnant (positive pregnancy test within 7 days of starting treatment), or lactating women.
11. Sexually active patients of child bearing potential not using adequate contraception (male and female)*.
12. Previous malignancies other than adequately treated in situ carcinoma of the uterine cervix or basal or squamous cell carcinoma of the skin, unless there has been a disease free interval of at least 10 years.
13. Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome or inability to take oral medication.
14. Chronic inflammatory bowel disease and/or bowel obstruction and/or active peptic ulcer, either of which have been active or required medication in the last 2 years.
15. History of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant precluding informed consent or interfering with compliance for oral drug intake.
16. Known dihydropyrimidine dehydrogenase (DPD) deficiency.
17. Patients with known allergy to Chinese hamster ovary cell proteins or other recombinant human or humanized antibodies or to any excipients of bevacizumab formulation; or to any other study drugs.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Disease free survival (3 year);Secondary Objective: - Disease free survival for stage III patients (3 years)<br>- Overall survival (5 year)<br>- Side effect profiles<br>- Translational science<br>;Primary end point(s): Disease-free survival on all patients<br>(Time from randomisation until confirmation of relapse or death from any cause)<br>;Timepoint(s) of evaluation of this end point: from randomisation until confirmation of relapse or death fram any cause

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - disease-free survival on stage III patients<br>- overall survival<br>- side effect profile<br>- translational science;Timepoint(s) of evaluation of this end point: - DFS: 3 years after the last patient recruitment<br>- OS: from randomisation until death from any cause

Related Trials