None listed
Conditions
Brief summary
This study looks at the effects of the drug capecitabine with or without bevacizumab in the treatment of patients with stage III colorectal cancer. You can join this study if you have cancer of the back passage (rectum) or large bowel (colon). Trial details: Participants will be divided into two groups. One group will receive oral capecitabine (from day 1 to day 14, rest for 7 days then repeat every 3 weekly for a total of 8 cycles), plus intravenous(IV) bevacizumab (one dose on day 1, repeated every 3 weekly for 16 cycles). The other group will receive capecitabine alone (from day 1 to day 14, rest for 7 days then repeat every 3 weekly for a total of 8 cycles), which is standard treatment. New preventative chemotherapies have been developed to reduce the risk of relapse of colorectal cancer. QUASAR2 uses a new combination of an oral chemotherapy drug (capecitabine) and a molecularly targeted therapy (bevacizumab), to determine whether this is more effective and less toxic than capecitabine alone. Colorectal cancer is the most commonly occurring cancer in Australia (excluding non-melanomic skin cancer), and the second most common cancer-related cause of death, responsible for 4,447 deaths in 2003 (1) As many as 40% of patients who undergo potentially curative treatment will ultimately relapse and die of metastatic disease. This observation has led to the development of adjuvant chemotherapies which reduce the risk of relapse. QUASAR2 uses a new combination for adjuvant therapy: an oral chemotherapy drug (capecitabine) and a molecularly targeted therapy (bevacizumab), to define whether this is superior in efficacy and less in toxicity than capecitabine alone, which is a standard of care in this disease.
Interventions
Intervention: Capecitabine 1250mg/m2 orally twice daily(total dose 0f 2500mg/m2) from day 1 to day 14, rest for 7 days then repeat every 3 weekly. Plus Bevacizumab 7.5mg/kg intravenous(IV)_ over 30-90 minutes, one dose on day 1, repeated every 3 weekly for 16 cycles.
Sponsors
Australiasia Gastro_Intestinal Trial Group (AGITG)
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
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) 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 Organisation (WHO) Performance Status 0 or 1. (5) Male or female outpatients age greater than or equal to 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.
Exclusion criteria
(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 <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 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.
Outcome results
None listed