Colorectal CancerPhase 2NCT01131078
A Study of Avastin (Bevacizumab) in Combination Chemotherapy in Patients With Metastatic Cancer of the Colon or Rectum
A Phase 2 study testing Bevacizumab [Avastin], Capecitabine and Irinotecan in people with Colorectal Cancer, run by Hoffmann-La Roche at 44 sites in Italy.
Trial summary
A study of Avastin (bevacizumab) in combination chemotherapy in patients with metastatic cancer of the colon or rectum. The anticipated time on study treatment is until disease progression. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- Bevacizumab [Avastin], Capecitabine and Irinotecan
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 306 participants
- Where
- 44 sitesItaly
- Study dates
- Jun 2005to Nov 2012
- Phase
- Phase 2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- adult patients >=18 years of age;
- colon or rectal cancer, with metastases;
- >=1 measurable lesion.
Who cannot join
- previous systemic treatment for advanced disease;
- radiotherapy to any site within 4 weeks before study;
- daily aspirin (>325 mg/day), anticoagulants, or other medications known to predispose to gastrointestinal ulceration;
- co-existing malignancies or malignancies diagnosed within last 5 years (except basal cell cancer or cervical cancer in situ).
Trial locations and contacts
44 sites in 1 country.
44 sites in 1 country
Italy44 sites
Study site
Ancona, The Marches, 60121
Study site
Benevento, Campania, 82100
Study site
Bologna, Emilia-Romagna, 40138
Study site
Bolzano, Trentino-Alto Adige, 39100
Study site
Brescia, Lombardy, 25123
Study site
Busto Arsizio, Lombardy, 21052
Study site
Cagliari, Sardinia, 09100
Study site
Camposampiero, Veneto, 35012
Study site
Carpi, Emilia-Romagna, 41012
Study site
Casalpusterlengo, Lombardy, 20071
Study site
Catania, Sicily, 95100
Study site
Cremona, Lombardy, 26100
Study site
Este, Veneto, 35042
Study site
Florence, Tuscany, 50139
Study site
Gorgonzola, Lombardy, 20064
Study site
Grosseto, Tuscany, 58100
Study site
Latina, Lazio, 04100
Study site
Latisana, Friuli Venezia Giulia, 33053
Study site
Lecco, Lombardy, 23900
Study site
Legnago, Lombardy, 37045
Study site
Mantua, Lombardy, 46100
Study site
Milan, Lombardy, 20121
Study site
Milan, Lombardy, 20133
Study site
Milan, Lombardy, 20142
Study site
Milan, Lombardy, 20162
Study site
Montecchio Maggiore, Veneto, 36075
Study site
Naples, Campania, 80136
Study site
Negrar, Veneto, 37024
Study site
Novara, Piedmont, 28100
Study site
Palermo, Sicily, 90127
Study site
Paola, Calabria, 87027
Study site
Pavia, Lombardy, 27100
Study site
Piacenza, Emilia-Romagna, 29100
Study site
Pisa, Tuscany, 56100
Study site
Prato, Tuscany, 59100
Study site
Rome, Lazio, 00168
Study site
Rome, Lazio, 00186
Study site
Saronno, Lombardy, 21047
Study site
Sondrio, Lombardy, 23100
Study site
Terni, Umbria, 05100
Study site
Treviglio, Lombardy, 24047
Study site
Turin, Piedmont, 10153
Study site
Udine, Friuli Venezia Giulia, 33100
Study site
Varese, Lombardy, 21100
About this study
Official title: A Randomized, Open-label Study Comparing the Effect of 3 Chemotherapy Regimens Containing Avastin on Time to Disease Progression in Patients With Metastatic Colorectal Cancer
A study of Avastin (bevacizumab) in combination chemotherapy in patients with metastatic cancer of the colon or rectum. The anticipated time on study treatment is until disease progression.
- Conditions
- Colorectal Cancer
- Being tested
- Bevacizumab [Avastin], Capecitabine, Irinotecan
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bevacizumab [Avastin]Drug
Also called Avastin
Bevacizumab was administered as a 7.5 mg/kg intravenous infusion over 30 to 90 minutes on Day 1 of each 3 week cycle.
CapecitabineDrug
Capecitabine was administered orally at a doses of 1000 or 1250, mg/m^2 twice daily (Day 2 to 15) or as 650 mg/m^2 twice daily on Days 1 to 21.
IrinotecanDrug
Irinotecan was administered as a 240 mg/m^2 intravenous infusion over 60 minutes (Day 1) every 3 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Bevacizumab + Irinotecan + Capecitabine (1000 mg/m^2) | Experimental | Bevacizumab was administered as a 7.5 mg/kg intravenous infusion over 30 to 90 minutes on Day 1 of each 3 week cycle. Irinotecan was administered as a 240 mg/m^2 intravenous infusion over 60 minutes (Day 1) every 3 weeks. Capecitabine was administered orally at a dose of 1000 mg/m^2 twice daily (Day 2 to 15). Cycle length was 3 weeks consisting of 2 weeks of capecitabine treatment followed by 1 week without treatment up to 6 cycles. After 6 cycles, participants with objective response or SD were treated with bevacizumab alone until unacceptable toxicity, PD, or participant withdrawal. Receives: Drug: Bevacizumab [Avastin]; Drug: Capecitabine; Drug: Irinotecan |
| Bevacizumab + Capecitabine (1250 mg/m^2) | Experimental | Bevacizumab was administered as a 7.5 mg/kg intravenous infusion over 30 to 90 minutes on Day 1 of each 3 week cycle in combination with capecitabine administered orally at 1250 mg/m^2 twice daily (Day 1 to 14). Cycle length was 3 weeks with 2 weeks of capecitabine treatment followed by 1 week without treatment up to 6 cycles. After 6 cycles, participants with objective response or SD were treated with bevacizumab alone until unacceptable toxicity, PD, or participant withdrawal. Receives: Drug: Bevacizumab [Avastin]; Drug: Capecitabine |
| Bevacizumab + Capecitabine (650 mg/m^2) | Experimental | Bevacizumab was administered as a 7.5 mg/kg intravenous infusion over 30 to 90 minutes on Day 1 of each 3 Week cycle in combination with capecitabine administered orally at 650 mg/m^2 twice daily (Day 1 to 21). Cycle length was 3 weeks with 3 weeks of capecitabine treatment without interruptions. Participants received the same regimen until unacceptable toxicity, PD, or participant withdrawal. Receives: Drug: Bevacizumab [Avastin]; Drug: Capecitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Disease Progression or Death
Disease progression was defined according to National Cancer Institute (NCI) guidelines and best clinical practices.
Measured: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Time to Progression (TTP)
TTP is defined as the time from date of randomization until objective tumor progression or death due to any cause. It includes deaths and thus can be correlated to overall survival.
Measured: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Secondary outcomes (15)
Percentage of Participants Who Died
Overall survival is defined as the time from date of randomization until death from any cause
Measured: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Overall Survival
Overall survival is defined as the time from date of randomization until death from any cause; Kaplan-Meier estimates were used for analysis.
Measured: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Percentage of Participants With Treatment Failure
Treatment failure is defined as discontinuation of treatment for any reason, including disease progression, death, treatment toxicity, insufficient therapeutic response, failure to return, refusing treatment, being unwilling to cooperate and withdrawing consent.
Measured: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Time to Treatment Failure
Time to treatment failure is defined as a composite endpoint measuring time from date of randomization to discontinuation of treatment for any reason, including disease progression, death, treatment toxicity, insufficient therapeutic response, failure to return, refusing treatment, being unwilling to cooperate and withdrawing consent. Analysis was performed using Kaplan-Meier estimates.
Measured: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Percentage of Participants With Progression Excluding Deaths
The failure event was defined as tumor progression excluding deaths due to any reason.
Measured: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Time to Progression Excluding Deaths
The failure event was defined as tumor progression excluding deaths due to any reason. Kaplan-Meier estimates were used for analysis.
Measured: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Percentage of Participants With Progression Excluding Deaths Not Related to Underlying Cancer
The failure event was defined as tumor progression excluding only deaths not related to underlying cancer.
Measured: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Time to Progression Excluding Deaths Not Related to Underlying Cancer
The failure event was defined as tumor progression excluding only deaths not related to underlying cancer. Kaplan-Meier estimates were used for analysis.
Measured: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Percentage of Participants by Best Overall Response
Best overall response is defined as the best response recorded from the date of randomization until disease progression or recurrence. Complete response (CR): at least 2 determinations of CR at least 4 weeks apart before progression; Partial response (PR): at least 2 determinations of PR at least 4 weeks apart before progression; Stable disease (SD): at least one SD assessment; Progressive Disease (PD): Disease progression or death due to underlying cancer. CR: Complete disappearance of all target lesions; PR: At least 30% decrease in the sum of the longest diameter of all target lesions taking as reference the baseline sum of all target lesions; PD: At least 20% decrease in the sum of the longest diameter of all target lesions taking as reference the baseline sum of longest diameter of all target lesions or the appearance of one or more new lesions; SD: Neither sufficient shrinkage to qualify for CR or PR or increase in lesions;
Measured: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Percentage of Participants With a Best Overall Response of CR or PR
CR: Complete disappearance of all target lesions; PR: At least 30% decrease in the sum of the longest diameter of all target lesions taking as reference the baseline sum of all target lesions;
Measured: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Percentage of Participants With Stable Disease
Stable disease rate was the proportion of participants who achieved CR, PR, or SD.
Measured: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Percentage of Participants With Progressive Disease Within 12 Weeks From Start of Treatment
Early progression was the proportion of participants with progressive disease within 12 weeks from the start of treatment.
Measured: Randomization, Weeks 3, 6 and 9, and 12
Duration of Overall Response
Duration of overall response included participants who achieved a CR or PR.
Measured: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Duration of Stable Disease (SD)
Duration of SD was calculated as the number of months the participants remained in CR, PR or SD. Kaplan-Meier estimates were used for analysis.
Measured: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Duration of Overall Complete Response
Duration of complete response was calculated as the time in months from the date of randomization to the date of first documentation of CR. Kaplan-Meier estimates were used for analysis.
Measured: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2010 (estimated)
- Study startJun 2005
- Primary completionNov 2012
- Study completionNov 2012
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.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 306 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study chair, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01131078
- Sponsor's protocol ID
- ML18524
- Status last verified
- Jun 2015
- First submitted
- 20 Apr 2010
- Last updated
- 4 Jun 2015
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open-label Study Comparing the Effect of 3 Chemotherapy Regimens Containing Avastin on Time to Disease Progression in Patients With Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT01131078
- Acronym / sponsor ID
- ML18524
- Conditions
- Colorectal Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 306 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- Jun 2005
- Primary completion
- Nov 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 26 May 2010 (estimated)
- Results
- Posted 31 Dec 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A study of Avastin (bevacizumab) in combination chemotherapy in patients with metastatic cancer of the colon or rectum. The anticipated time on study treatment is until disease progression.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Bevacizumab + Irinotecan + Capecitabine (1000 mg/m^2) | Experimental | Drug: Bevacizumab [Avastin], Drug: Capecitabine, Drug: IrinotecanBevacizumab was administered as a 7.5 mg/kg intravenous infusion over 30 to 90 minutes on Day 1 of each 3 week cycle. Irinotecan was administered as a 240 mg/m^2 intravenous infusion over 60 minutes (Day 1) every 3 weeks. Capecitabine was administered orally at a dose of 1000 mg/m^2 twice daily (Day 2 to 15). Cycle length was 3 weeks consisting of 2 weeks of capecitabine treatment followed by 1 week without treatment up to 6 cycles. After 6 cycles, participants with objective response or SD were treated with bevacizumab alone until unacceptable toxicity, PD, or participant withdrawal. |
| Bevacizumab + Capecitabine (1250 mg/m^2) | Experimental | Drug: Bevacizumab [Avastin], Drug: CapecitabineBevacizumab was administered as a 7.5 mg/kg intravenous infusion over 30 to 90 minutes on Day 1 of each 3 week cycle in combination with capecitabine administered orally at 1250 mg/m^2 twice daily (Day 1 to 14). Cycle length was 3 weeks with 2 weeks of capecitabine treatment followed by 1 week without treatment up to 6 cycles. After 6 cycles, participants with objective response or SD were treated with bevacizumab alone until unacceptable toxicity, PD, or participant withdrawal. |
| Bevacizumab + Capecitabine (650 mg/m^2) | Experimental | Drug: Bevacizumab [Avastin], Drug: CapecitabineBevacizumab was administered as a 7.5 mg/kg intravenous infusion over 30 to 90 minutes on Day 1 of each 3 Week cycle in combination with capecitabine administered orally at 650 mg/m^2 twice daily (Day 1 to 21). Cycle length was 3 weeks with 3 weeks of capecitabine treatment without interruptions. Participants received the same regimen until unacceptable toxicity, PD, or participant withdrawal. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- adult patients >=18 years of age;
- colon or rectal cancer, with metastases;
- >=1 measurable lesion.
Key exclusion criteria (4 listed)
- previous systemic treatment for advanced disease;
- radiotherapy to any site within 4 weeks before study;
- daily aspirin (>325 mg/day), anticoagulants, or other medications known to predispose to gastrointestinal ulceration;
- co-existing malignancies or malignancies diagnosed within last 5 years (except basal cell cancer or cervical cancer in situ).
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 |
|---|---|---|
| Bevacizumab [Avastin]Also: AvastinBevacizumab was administered as a 7.5 mg/kg intravenous infusion over 30 to 90 minutes on Day 1 of each 3 week cycle. | Drug | Bevacizumab + Capecitabine (1250 mg/m^2), Bevacizumab + Capecitabine (650 mg/m^2), Bevacizumab + Irinotecan + Capecitabine (1000 mg/m^2) |
| CapecitabineCapecitabine was administered orally at a doses of 1000 or 1250, mg/m^2 twice daily (Day 2 to 15) or as 650 mg/m^2 twice daily on Days 1 to 21. | Drug | Bevacizumab + Capecitabine (1250 mg/m^2), Bevacizumab + Capecitabine (650 mg/m^2), Bevacizumab + Irinotecan + Capecitabine (1000 mg/m^2) |
| IrinotecanIrinotecan was administered as a 240 mg/m^2 intravenous infusion over 60 minutes (Day 1) every 3 weeks. | Drug | Bevacizumab + Irinotecan + Capecitabine (1000 mg/m^2) |
Primary outcome
Percentage of Participants With Disease Progression or Death
Time frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Disease progression was defined according to National Cancer Institute (NCI) guidelines and best clinical practices.
Time to Progression (TTP)
Time frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
TTP is defined as the time from date of randomization until objective tumor progression or death due to any cause. It includes deaths and thus can be correlated to overall survival.
15 secondary outcomes
Percentage of Participants Who Died
Time frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Overall Survival
Time frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Percentage of Participants With Treatment Failure
Time frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Time to Treatment Failure
Time frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Percentage of Participants With Progression Excluding Deaths
Time frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Time to Progression Excluding Deaths
Time frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Percentage of Participants With Progression Excluding Deaths Not Related to Underlying Cancer
Time frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Time to Progression Excluding Deaths Not Related to Underlying Cancer
Time frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Percentage of Participants by Best Overall Response
Time frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Percentage of Participants With a Best Overall Response of CR or PR
Time frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Percentage of Participants With Stable Disease
Time frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Percentage of Participants With Progressive Disease Within 12 Weeks From Start of Treatment
Time frame: Randomization, Weeks 3, 6 and 9, and 12
Duration of Overall Response
Time frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Duration of Stable Disease (SD)
Time frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death
Duration of Overall Complete Response
Time frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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 chair
Hoffmann-La Roche
44 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bevacizumab [Avastin], Capecitabine and Irinotecan in people with Colorectal Cancer, run by Hoffmann-La Roche at 44 sites in Italy.
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 3 inclusion and 4 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 4 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 44 sites in Italy. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 31 Dec 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?
Percentage of Participants With Disease Progression or Death (time frame: Randomization, Weeks 3, 6 and 9, and every 3 months up to 5 years or Death). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Jun 2015.