Multicentre international study of capecitabine ± bevacizumab as adjuvant treatment of colorectal cancer
| ISRCTN | ISRCTN45133151 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN45133151 |
| Secondary identifying numbers | N/A |
- Submission date
- 01/12/2003
- Registration date
- 10/12/2003
- Last edited
- 02/09/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Contact information
Prof David J Kerr
Scientific
Scientific
QUASAR 2
Oncology Clinical Trials Office (OCTO)
Department of Clinical Pharmacology
Old Road Campus Research Building
University of Oxford
Old Road Campus
off Roosevelt Drive
Headington
Oxford
OX3 7DQ
United Kingdom
| Phone | +44 (0)1865 617021 |
|---|---|
| quasar2@octo-oxford.org.uk |
Study information
| Study design | Randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | Multicentre international study of capecitabine ± bevacizumab as adjuvant treatment of colorectal cancer |
| Study acronym | QUASAR 2 |
| Study objectives | Study hypothesis added as of 18/07/2007: Treatment with a combination of capecitabine plus bevacizumab results in better disease-free survival (DFS) than treatment with capecitabine alone. Please note that the trial title provided at time of registration was "QUASAR 2 Multicentre international study of capecitabine +/- bevacizumab as adjuvant treatment of colon cancer". The current trial title was added as of 02/07/2007. |
| Ethics approval(s) | Metropolitan Multi-centre Research Ethics Committee, 03/09/2004, ref: 04/MRE11/18 |
| Health condition(s) or problem(s) studied | Colorectal cancer |
| Intervention | 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 daily dose 5000 mg]). Treatment is repeated every 3 weeks for a total of eight cycles (24 weeks). One cycle = 3 weeks. Arm B (experimental 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 daily [max total daily dose 5000 mg]).Treatment is repeated every 3 weeks for a total of eight cycles (24 weeks). One cycle = 3 weeks. Bevacizumab 7.5 mg/kg will be administered initially over a 90 (±15) minute period on day 1. The infusion will be repeated every 3 weeks for a total of 16 cycles (48 weeks). One cycle = three weeks. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Capecitabine, bevacizumab |
| Primary outcome measure | Primary outcome measure added as of 28/06/2007: Disease-free survival at 3 years. |
| Secondary outcome measures | 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 |
| Overall study start date | 01/07/2005 |
| Completion date | 31/12/2011 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Target number of participants added as of 29/06/2007: 2240 patients |
| Total final enrolment | 1952 |
| Key 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 |
| Key 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 <30 ml/min [calculated according to Cockroft-Gault formula]). 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 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 ml/min [calculated according to Cockroft-Gault formula]) 4. Any of the following laboratory values (tests should not have been carried out more than two weeks prior to randomisation): 4.1. Absolute neutrophil count (ANC) <1.5 x 10^9/l 4.2. Platelet count <100 x 10^9/l 4.3. Total bilirubin >1.5 Upper Limit of Normal (ULN) 4.4. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) >2.5 x ULN 4.5. Alkaline phosphatase >2.5 x ULN 5. Subjects 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 seven 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 ten 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. 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 18. 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. |
| Date of first enrolment | 01/07/2005 |
| Date of final enrolment | 31/12/2011 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
University of Oxford
Oxford
OX3 7DQ
United Kingdom
OX3 7DQ
United Kingdom
Sponsor information
University of Oxford (UK)
University/education
University/education
University Offices
Wellington Square
Oxford
OX1 2JD
England
United Kingdom
| Phone | +44 (0)1865 270 000 |
|---|---|
| research.services@admin.ox.ac.uk | |
"ROR" |
https://ror.org/052gg0110 |
Funders
Funder type
Industry
Hoffman La Roche Inc. (ref: MO17092) (International)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan | Not provided at time of registration |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/11/2016 | Yes | No | |
| Plain English results | 02/09/2022 | No | Yes |
Editorial Notes
02/09/2022: Cancer Research UK plain English results link and total final enrolment added.
26/09/2016: Publication reference added.
