Condition category
Cancer
Date applied
01/12/2003
Date assigned
10/12/2003
Last edited
26/09/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Prof David J Kerr

ORCID ID

Contact details

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
+44 (0)1865 617021
quasar2@octo-oxford.org.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

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

Acronym

QUASAR 2

Study hypothesis

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

Metropolitan Multi-centre Research Ethics Committee, 03/09/2004, ref: 04/MRE11/18

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

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

Phase

Phase III

Drug names

Capecitabine, bevacizumab

Primary outcome measures

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 trial start date

01/07/2005

Overall trial end date

31/12/2011

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Target number of participants added as of 29/06/2007: 2240 patients

Participant 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.

Recruitment start date

01/07/2005

Recruitment end date

31/12/2011

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University of Oxford
Oxford
OX3 7DQ
United Kingdom

Sponsor information

Organisation

University of Oxford (UK)

Sponsor details

University Offices
Wellington Square
Oxford
OX1 2JD
United Kingdom
+44 (0)1865 270 000
research.services@admin.ox.ac.uk

Sponsor type

University/education

Website

Funders

Funder type

Industry

Funder name

Hoffman La Roche Inc. (ref: MO17092) (International)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2016 results in: https://www.ncbi.nlm.nih.gov/pubmed/27660192

Publication citations

Additional files

Editorial Notes

26/09/2016: Publication reference added.