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

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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Bevacizumab; Drug: Capecitabine

• Study Type: Interventional
• Enrollment (Actual): 280
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria, 6020
  • Linz, Austria, 4010
  • Salzburg, Austria, 5020
  • Wien, Austria, 1160
  • Wien, Austria, 1220
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
  • Ontario
    • London, Ontario, Canada, N6A 4L6
    • Ottawa, Ontario, Canada, K1H 8L6
    • Toronto, Ontario, Canada, M4N 3M5
    • Toronto, Ontario, Canada, M5B 1W8
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
• Greece
  • Larissa, Greece, 41 110
  • Piraeus, Greece, 18537
• Hungary
  • Budapest, Hungary, 1122
  • Budapest, Hungary, 1083
  • Gyor, Hungary, 9023
  • Zalaegerszeg-Pozva, Hungary, 8900
• Italy
  • Emilia-Romagna
    • Reggio Emilia, Emilia-Romagna, Italy, 42100
  • Lazio
    • Roma, Lazio, Italy, 00144
  • Puglia
    • Lecce, Puglia, Italy, 73100
  • Toscana
    • Firenze, Toscana, Italy, 50139
• Korea, Republic of
  • Gyeonggi-do, Korea, Republic of, 410-769
  • Incheon, Korea, Republic of, 405-760
  • Seoul, Korea, Republic of, 110-744
  • Seoul, Korea, Republic of, 135-710
• Mexico
  • Leon, Mexico, 37000
  • Mexico City, Mexico, 14000
  • Mexico City, Mexico, 14140
  • Mexico City, Mexico, 16200
  • Puebla, Mexico, 72530
• Netherlands
  • Apeldoorn, Netherlands, 7334 DZ
  • Eindhoven, Netherlands, 5623 EJ
  • Utrecht, Netherlands, 3527 CE
• Poland
  • Krakow, Poland, 30-501
  • Krakow, Poland, 31-826
  • Warszawa, Poland, 02-097
• Slovenia
  • Ljubljana, Slovenia, 1000
• Spain
  • Barcelona, Spain, 08041
  • Jaen, Spain, 23007
  • Madrid, Spain, 28040
  • Murcia, Spain, 30120
  • Zaragoza, Spain, 50009
  • Las Palmas
    • Las Palmas de Gran Canaria, Las Palmas, Spain, 35016
  • Madrid
    • Leganes, Madrid, Spain, 28911
• United Kingdom
  • Bristol, United Kingdom, BS2 8ED
  • Colchester, United Kingdom, CO3 3NB
  • Glasgow, United Kingdom, G12 0YN
  • Leicester, United Kingdom, LE1 5WW
  • London, United Kingdom, W2 1NY
  • Manchester, United Kingdom, M20 4BX
  • Nottingham, United Kingdom, NG5 1PB
  • Rhyl, United Kingdom, LL18 5UJ
  • Sutton, United Kingdom, SM2 5PT

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: June 11, 2007
• First Submitted That Met QC Criteria: June 11, 2007
• First Posted (Estimate): June 12, 2007

Study Record Updates

• Last Update Posted (Estimate): January 8, 2015
• Last Update Submitted That Met QC Criteria: January 7, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Capecitabine; Bevacizumab
• Other Study ID Numbers: MO19286

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No