Colorectal cancer Cancer Colorectal cancer
Conditions
Interventions
Randomised to:
Arm A (standard arm)
Capecitabine 1250 mg/m^2, twice daily 12 hours apart (total daily dose 2500 mg/m^2) for 14 days (max 2500 mg twice a day [bd] [total
Sponsors
University of Oxford (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria amended as of 02/07/2007: 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) 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. 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. World Health Organization Performance Status 0 or 1. 5. Male or female outpatients age 18 years. 6. Written informed consent given. 7. Life expectancy of greater than or equal to 5 years, in terms of non-cancer-related morbidity. *Calculation of these dates is based on date of surgery being day 1. Inclusion criteria provided at time of registration: 1. Histologically proven stage III and high risk stage II (any of the following - stage T4, or lymphatic invasion, vascular invasion, peritoneal involvement) colon cancer (expected ratio 70%:30%) 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. World Health Organisation (WHO) Performance Status 0 or 1 5. Male or female outpatients age =18 years 6. Written informed consent given 7. Life expectancy of =5 years
Exclusion criteria
Exclusion criteria: Exclusion criteria amended as of 02/07/2007: 1. Previous chemotherapy, immunotherapy or infra-diaphragmatic radiotherapy. 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 1.5 Upper Limit of Normal (ULN) d. Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) > 2.5 x ULN e. Alkaline phosphatase > 2.5 x ULN 5. Patients requiring chronic use of full dose oral or parenteral anticoagulants, high dose aspirin (>325 mg/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 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. 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. 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. ** Women of childbearing potential randomised to receive bevacizumab are required to have a serum pregnancy test at baseline (i.e. prior to starting treatment). Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential. Exclusion criteria provided at time of registration: 1. Previous chemotherapy or immunotherapy 2. Received any investigational drug or agent/procedure i.e. participation in another treatment trial within four weeks of randomisation 3. Moderate or severe renal impairment (creatinine clearance =30
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary outcome measure added as of 28/06/2007: Disease-free survival at 3 years. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary outcome measures added as of 28/06/2007: 1. Disease-free survival for stage III patients at 3 years 2. Overall survival at 5 years 3. Side effect profiles 4. Translational science | — |
Countries
England, United Kingdom
Outcome results
None listed