EudraCT number: 2005-000629-32
Sponsor: University of Oxford
A multicentre international study of capecitabine ± bevacizumab as adjuvant treatment of colorectal cancer.
QUASAR 2 is a study comparing 'standard' chemotherapy using capecitabine, against capecitabine + Avastin® (bevacizumab) with the expectation that adding bevacizumab to capecitabine may have the potential for improved relapse free and overall survival compared to capecitabine alone.
Summary of Results:
Recruitment into QUASAR 2 is now closed.
Primary endpoint: (3Y DFS stage II & III) target of 1892 patients: met 26 May 2010.
Secondary endpoint: (3Y DFS stage III only) target of 1411 stage III patients: 1206 randomised by close of recruitment (Oct 2010).
Number of sites: UK - 116, Non-UK - 54
- 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 tumour 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. N.B. Recruitment of stage II patients closed
- Patients must have undergone complete resection of the primary tumour without evidence of residual disease.
- 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].
- WHO Performance Status 0 or 1.
- Male or female outpatients age >= 18 years.
- Written informed consent given.
- Life expectancy of >=5 years, in terms of non-cancer-related morbidity.
- 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.
- Received any investigational drug or agent/procedure, (i.e. participation in another treatment trial) within 4 weeks of randomisation.
- Moderate or severe renal impairment [creatinine clearance <30ml/min (calculated according to Cockroft-Gault formula–see Appendix 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)
- 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. Low dose clopidogrel (≤75mg) is allowed.
- Proteinuria > 500 mg/24 hours.
- Known coagulopathy.
- 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].
Concomitant treatment with sorivudine or its chemically related analogues such as brivudine.
- Pregnant (positive pregnancy test within 7 days of starting treatment), or lactating women.
- Sexually active patients of child bearing potential not using adequate contraception (male and female)**.
- 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.
- Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome or inability to take oral medication.
- 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.
- 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.
- 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.
* Calculation of these dates is based on date of surgery being day 1.
** 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.
- Disease free survival
- Overall survival Side effect profile
Accrual completion: September 2010
Trial completion: September 2014