Colorectal CancerPhase 3NCT00484939
A Study of Bevacizumab (Avastin) in Combination With Capecitabine (Xeloda) in Elderly Patients With Metastatic Colorectal Cancer
A Phase 3 study testing Bevacizumab and Capecitabine in people with Colorectal Cancer, run by Hoffmann-La Roche at 55 sites in 12 countries.
Trial summary
This 2-arm study assessed the efficacy and safety of bevacizumab (Avastin) in combination with capecitabine (Xeloda), compared with capecitabine alone, in elderly patients with metastatic colorectal cancer. Read more about this study
- Who is it for?
- Ages 70 years and older
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- Bevacizumab and Capecitabine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 280 participants
- Where
- 55 sitesin 12 countries
- Study dates
- Jul 2007to Mar 2013
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 70 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Adult patients, ≥ 70 years of age.
- Cancer of the colon or rectum.
- Metastatic disease diagnosed ≤ 6 months before enrollment.
- ≥ 1 measurable metastatic lesion.
Who cannot join
- Adjuvant anti-vascular endothelial growth factor (VEGF) treatment.
- Prior chemotherapeutic treatment for metastatic colorectal cancer.
- Past or current history of other malignancies (with the exception of basal and squamous cell cancer of the skin, or in situ cancer of the cervix).
- Clinically significant cardiovascular disease.
- Current or recent daily use of aspirin (> 325 mg/day) or other non-steroidal anti-inflammatory drug (NSAID), or full dose anticoagulants.
Trial locations and contacts
55 sites in 12 countries.
55 sites in 12 countries
United Kingdom9 sites
Study site
Bristol, BS2 8ED
Study site
Colchester, CO3 3NB
Study site
Glasgow, G12 0YN
Study site
Leicester, LE1 5WW
Study site
London, W2 1NY
Study site
Manchester, M20 4BX
Study site
Nottingham, NG5 1PB
Study site
Rhyl, LL18 5UJ
Study site
Sutton, SM2 5PT
Canada8 sites
Study site
Calgary, Alberta, T2N 4N2
Study site
Halifax, Nova Scotia, B3H 2Y9
Study site
London, Ontario, N6A 4L6
Study site
Montreal, Quebec, H3T 1E2
Study site
Ottawa, Ontario, K1H 8L6
Study site
Toronto, Ontario, M4N 3M5
Study site
Toronto, Ontario, M5B 1W8
Study site
Vancouver, British Columbia, V5Z 4E6
Spain7 sites
Study site
Barcelona, Barcelona, 08041
Study site
Jaén, Jaen, 23007
Study site
Las Palmas de Gran Canaria, Las Palmas, 35016
Study site
Leganés, Madrid, 28911
Study site
Madrid, Madrid, 28040
Study site
Murcia, Murcia, 30120
Study site
Zaragoza, Zaragoza, 50009
Austria5 sites
Study site
Innsbruck, 6020
Study site
Linz, 4010
Study site
Salzburg, 5020
Study site
Vienna, 1160
Study site
Vienna, 1220
Mexico5 sites
Study site
León, 37000
Study site
Mexico City, 14000
Study site
Mexico City, 14140
Study site
Mexico City, 16200
Study site
Puebla City, 72530
Hungary4 sites
Study site
Budapest, 1083
Study site
Budapest, 1122
Study site
Győr, 9023
Study site
Zalaegerszeg-Pozva, 8900
Italy4 sites
Study site
Florence, Tuscany, 50139
Study site
Lecce, Apulia, 73100
Study site
Reggio Emilia, Emilia-Romagna, 42100
Study site
Rome, Lazio, 00144
South Korea4 sites
Study site
Gyeonggi-do, 410-769
Study site
Incheon, 405-760
Study site
Seoul, 110-744
Study site
Seoul, 135-710
Netherlands3 sites
Study site
Apeldoorn, 7334 DZ
Study site
Eindhoven, 5623 EJ
Study site
Utrecht, 3527 CE
Poland3 sites
Study site
Krakow, 30-501
Study site
Krakow, 31-826
Study site
Warsaw, 02-097
About this study
Official title: A Randomised, Open-label Phase III Study to Assess Efficacy and Safety of Bevacizumab in Combination With Capecitabine as First-line Treatment for Elderly Patients With Metastatic Colorectal Cancer
This 2-arm study assessed the efficacy and safety of bevacizumab (Avastin) in combination with capecitabine (Xeloda), compared with capecitabine alone, in elderly patients with metastatic colorectal cancer. Patients were randomized to receive either bevacizumab (7.5 mg/kg intravenously on Day 1 of each 3-week cycle) in combination with capecitabine (1000 mg/m^2 orally twice a day on Days 1-14 of each 3-week cycle) or capecitabine (1000 mg/m^2 orally twice a day on Days 1-14 of each 3-week cycle) alone.
No notable trends or interactions in laboratory values, electrocardiogram, or vital signs suggesting an effect in either direction for capecitabine/bevacizumab combination therapy or capecitabine monotherapy were observed during the study.
- Conditions
- Colorectal Cancer
- Being tested
- Bevacizumab, Capecitabine
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BevacizumabDrug
Also called Avastin
Treatment continued until unacceptable toxicity, withdrawal of consent, disease progression, or a decision to terminate at the discretion of the Investigator if medically indicated. Bevacizumab was supplied in single-use vials.
CapecitabineDrug
Also called Xeloda
Treatment continued until unacceptable toxicity, withdrawal of consent, disease progression, or a decision to terminate at the discretion of the Investigator if medically indicated. Capecitabine was supplied as tablets.
| Study group | Role | What they receive |
|---|---|---|
| Bevacizumab + capecitabine | Experimental | Participants received bevacizumab 7.5 mg/kg intravenously on Day 1 of each 3-week treatment cycle. In addition, participants received capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 3-week treatment cycle. Receives: Drug: Bevacizumab; Drug: Capecitabine |
| Capecitabine | Active comparator | Participants received capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 3-week treatment cycle. Receives: Drug: Capecitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival
Progression-free survival was defined as the time in months from the date of randomization to the date of disease progression or death from any cause, whichever occurred first. All measurable lesions (maximum of 5 per organ and 10 in total, those with the longest diameter and suitability for accurate repeated measurements) were identified as target lesions (TL). A sum of the longest diameter for all TLs was calculated and reported as the baseline sum longest diameter (SLD). All other lesions were identified as non-TLs and recorded at baseline. PD was defined as ≥ 20% increase in the sum of the longest diameter of TLs, taking as reference the smallest SLD recorded since treatment started, the unequivocal progression of existing non-TLs, or the appearance of 1 or more new lesions.
Measured: Baseline to the end of the study (up to 5 years 8 months)
Secondary outcomes (8)
Best Overall Response (BOR)
BOR was defined as the best response (complete response [CR], partial response [PR], stable disease [SD], progressive disease [PD], not evaluable [NE], or not assessed [NA]) recorded from the start of study treatment until disease progression (PD) or death. CR was defined as the disappearance of all target (TL) and non-target lesions (non-TL). PR was defined as ≥ 30% decrease in the sum of the longest diameter (SLD) of TLs, taking as reference the baseline SLD, or the persistence of 1 or more non-TLs. For TLs, SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SLD since treatment started. For non-TLs, SD was defined as the persistence of 1 or more lesions. PD was defined as ≥ 20% increase in the sum of the longest diameter of TLs, taking as reference the smallest SLD recorded since treatment started, the unequivocal progression of existing non-TLs, or the appearance of 1 or more new lesions.
Measured: Baseline to the end of the study (up to 5 years 8 months)
Duration of Response
Duration of response was defined as the time in months from the first confirmed complete response (CR) or partial response (PR) until disease progression or death from any cause, whichever occurred first. CR was defined as the disappearance of all target (TL) and non-target lesions (non-TL). PR was defined as ≥ 30% decrease in the sum of the longest diameter (SLD) of TLs, taking as reference the baseline SLD, or the persistence of 1 or more non-TLs.
Measured: Baseline to the end of the study (up to 5 years 8 months)
Time to Response
Time to response was defined as the time in months from the date of first study treatment to the date of the first documentation of complete response (CR) or partial response (PR), whichever occurred first. CR was defined as the disappearance of all target (TL) and non-target lesions (non-TL). PR was defined as ≥ 30% decrease in the sum of the longest diameter (SLD) of TLs, taking as reference the baseline SLD, or the persistence of 1 or more non-TLs. Participants who did not have a confirmed response were censored at the date of the last evaluable tumor assessment, or if that was unavailable, at the date of the first dose of study medication.
Measured: Baseline to the end of the study (up to 5 years 8 months)
Overall Survival
Overall survival was defined as the time in months from randomization to death from any cause.
Measured: Baseline to the end of the study (up to 5 years 8 months)
Eastern Cooperative Oncology Group (ECOG) Performance Status
The ECOG performance status is a scale used to quantify cancer patients' general well-being and activities of daily life. The scale ranges from 0 to 5, with 0 denoting perfect health and 5 indicating death. The 6 categories are 0=Asymptomatic (Fully active, able to carry on all predisease activities without restriction), 1=Symptomatic but completely ambulatory (Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature), 2=Symptomatic, < 50% in bed during the day (Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours), 3=Symptomatic, > 50% in bed, but not bedbound (Capable of only limited self-care, confined to bed or chair 50% or more of waking hours), 4=Bedbound (Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair), 5=Death. Reported is the percentage of participants in each of the 6 ECOG performance status categories.
Measured: Baseline to the Safety Follow-up which occurred 28 days after the last dose of treatment (up to 5 years 8 months).
Percentage of Participants Requiring Additional Treatment for Malignancy
Reported is the percentage of participants requiring additional treatment for malignancy in the survival follow-up period.
Measured: Baseline to the end of the study (up to 5 years 8 months)
Duration of Follow-up
Duration of follow-up is defined as the time in days from randomization until disease progression or death, or time to censoring for overall survival.
Measured: Baseline to the end of the study (up to 5 years 8 months)
AEs, Laboratory Parameters, Vital Signs
Measured: Throughout study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2007 (estimated)
- Study startJul 2007
- Primary completionMar 2013
- Study completionMar 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 280 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00484939
- Sponsor's protocol ID
- MO19286
- Status last verified
- Jan 2015
- First submitted
- 11 Jun 2007
- Last updated
- 8 Jan 2015
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Cunningham D, Lang I, Marcuello E, Lorusso V, Ocvirk J, Shin DB, Jonker D, Osborne S, Andre N, Waterkamp D, Saunders MP; AVEX study investigators. Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial. Lancet Oncol. 2013 Oct;14(11):1077-1085. doi: 10.1016/S1470-2045(13)70154-2. Epub 2013 Sep 10.
PubMed 24028813
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Open-label Phase III Study to Assess Efficacy and Safety of Bevacizumab in Combination With Capecitabine as First-line Treatment for Elderly Patients With Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT00484939
- Acronym / sponsor ID
- MO19286
- Conditions
- Colorectal Cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 280 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- Jul 2007
- Primary completion
- Mar 2013 (actual)
- Study completion
- Mar 2013 (actual)
- First posted
- 12 Jun 2007 (estimated)
- Results
- Posted 10 Jun 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This 2-arm study assessed the efficacy and safety of bevacizumab (Avastin) in combination with capecitabine (Xeloda), compared with capecitabine alone, in elderly patients with metastatic colorectal cancer. Patients were randomized to receive either bevacizumab (7.5 mg/kg intravenously on Day 1 of each 3-week cycle) in combination with capecitabine (1000 mg/m^2 orally twice a day on Days 1-14 of each 3-week cycle) or capecitabine (1000 mg/m^2 orally twice a day on Days 1-14 of each 3-week cycle) alone.
No notable trends or interactions in laboratory values, electrocardiogram, or vital signs suggesting an effect in either direction for capecitabine/bevacizumab combination therapy or capecitabine monotherapy were observed during the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Bevacizumab + capecitabine | Experimental | Drug: Bevacizumab, Drug: CapecitabineParticipants received bevacizumab 7.5 mg/kg intravenously on Day 1 of each 3-week treatment cycle. In addition, participants received capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 3-week treatment cycle. |
| Capecitabine | Active comparator | Drug: CapecitabineParticipants received capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 3-week treatment cycle. |
Who may qualify
- Ages
- 70 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (4 listed)
- Adult patients, ≥ 70 years of age.
- Cancer of the colon or rectum.
- Metastatic disease diagnosed ≤ 6 months before enrollment.
- ≥ 1 measurable metastatic lesion.
Key exclusion criteria (5 listed)
- Adjuvant anti-vascular endothelial growth factor (VEGF) treatment.
- Prior chemotherapeutic treatment for metastatic colorectal cancer.
- Past or current history of other malignancies (with the exception of basal and squamous cell cancer of the skin, or in situ cancer of the cervix).
- Clinically significant cardiovascular disease.
- Current or recent daily use of aspirin (> 325 mg/day) or other non-steroidal anti-inflammatory drug (NSAID), or full dose anticoagulants.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BevacizumabAlso: AvastinTreatment continued until unacceptable toxicity, withdrawal of consent, disease progression, or a decision to terminate at the discretion of the Investigator if medically indicated. Bevacizumab was supplied in single-use vials. | Drug | Bevacizumab + capecitabine |
| CapecitabineAlso: XelodaTreatment continued until unacceptable toxicity, withdrawal of consent, disease progression, or a decision to terminate at the discretion of the Investigator if medically indicated. Capecitabine was supplied as tablets. | Drug | Bevacizumab + capecitabine, Capecitabine |
Primary outcome
Progression-free Survival
Time frame: Baseline to the end of the study (up to 5 years 8 months)
Progression-free survival was defined as the time in months from the date of randomization to the date of disease progression or death from any cause, whichever occurred first. All measurable lesions (maximum of 5 per organ and 10 in total, those with the longest diameter and suitability for accurate repeated measurements) were identified as target lesions (TL). A sum of the longest diameter for all TLs was calculated and reported as the baseline sum longest diameter (SLD). All other lesions were identified as non-TLs and recorded at baseline. PD was defined as ≥ 20% increase in the sum of the longest diameter of TLs, taking as reference the smallest SLD recorded since treatment started, the unequivocal progression of existing non-TLs, or the appearance of 1 or more new lesions.
8 secondary outcomes
Best Overall Response (BOR)
Time frame: Baseline to the end of the study (up to 5 years 8 months)
Duration of Response
Time frame: Baseline to the end of the study (up to 5 years 8 months)
Time to Response
Time frame: Baseline to the end of the study (up to 5 years 8 months)
Overall Survival
Time frame: Baseline to the end of the study (up to 5 years 8 months)
Eastern Cooperative Oncology Group (ECOG) Performance Status
Time frame: Baseline to the Safety Follow-up which occurred 28 days after the last dose of treatment (up to 5 years 8 months).
Percentage of Participants Requiring Additional Treatment for Malignancy
Time frame: Baseline to the end of the study (up to 5 years 8 months)
Duration of Follow-up
Time frame: Baseline to the end of the study (up to 5 years 8 months)
AEs, Laboratory Parameters, Vital Signs
Time frame: Throughout study
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24028813Cunningham D, Lang I, Marcuello E, Lorusso V, Ocvirk J, Shin DB, Jonker D, Osborne S, Andre N, Waterkamp D, Saunders MP; AVEX study investigators. Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial. Lancet Oncol. 2013 Oct;14(11):1077-1085. doi: 10.1016/S1470-2045(13)70154-2. Epub 2013 Sep 10.
Related trials for Colorectal Cancer
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingObservational study
Pre- and On-treatment Multi-omics Profiling of Locally Advanced Rectal Cancer
Rectal Neoplasms
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 2
Tislelizumab in People With Colorectal Cancer
Colorectal Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
55 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Bevacizumab and Capecitabine in people with Colorectal Cancer, run by Hoffmann-La Roche at 55 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jan 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 55 sites in United Kingdom, Canada, Spain, Austria, Mexico and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Jun 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free Survival (time frame: Baseline to the end of the study (up to 5 years 8 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00484939, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2015.