A Study of Bevacizumab (Avastin) in Combination With Capecitabine (Xeloda) in Elderly Patients With Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: Bevacizumab
* Drug: Capecitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients, ≥ 70 years of age. Cancer of the colon or rectum. Metastatic disease diagnosed ≤ 6 months before enrollment. ≥ 1 measurable metastatic lesion. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bevacizumab + capecitabine<br>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. | Drug: Bevacizumab<br>* 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.<br>* Other names: Avastin;Drug: Capecitabine<br>* 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.<br>* Other names: Xeloda;|
| Active Comparator: Capecitabine<br>Participants received capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 3-week treatment cycle. | Drug: Capecitabine<br>* 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.<br>* Other names: Xeloda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline to the end of the study (up to 5 years 8 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 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. | 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. | 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. | 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. | 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. | Baseline to the end of the study (up to 5 years 8 months) | 
| AEs, Laboratory Parameters, Vital Signs |  | Throughout study |