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

• ClinicalTrials.gov Identifier: NCT00484939
• Recruitment Status: Completed
• First Posted: June 12, 2007
• Results First Posted: June 10, 2014
• Last Update Posted: January 8, 2015
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: June 11, 2007
• First Posted Date: June 12, 2007
• Results First Submitted Date: March 7, 2014
• Results First Posted Date: June 10, 2014
• Last Update Posted Date: January 8, 2015
• Study Start Date: July 2007
• Actual Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 28, 2014)

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.

• Original Primary Outcome Measures (submitted: June 11, 2007): Progression-free survival

Current Secondary Outcome Measures (submitted: January 7, 2015)

• Best Overall Response (BOR) [ Time Frame: Baseline to the end of the study (up to 5 years 8 months) ]
  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.
• Duration of Response [ Time Frame: Baseline to the end of the study (up to 5 years 8 months) ]
  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.
• Time to Response [ Time Frame: Baseline to the end of the study (up to 5 years 8 months) ]
  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.
• Overall Survival [ Time Frame: Baseline to the end of the study (up to 5 years 8 months) ]
  Overall survival was defined as the time in months from randomization to death from any cause.
• 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). ]
  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.
• Percentage of Participants Requiring Additional Treatment for Malignancy [ Time Frame: Baseline to the end of the study (up to 5 years 8 months) ]
  Reported is the percentage of participants requiring additional treatment for malignancy in the survival follow-up period.
• Duration of Follow-up [ Time Frame: Baseline to the end of the study (up to 5 years 8 months) ]
  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.
• AEs, Laboratory Parameters, Vital Signs [ Time Frame: Throughout study ]

• Original Secondary Outcome Measures (submitted: June 11, 2007): Efficacy: Best overall response, duration of response, time to response, overall survival. Safety: Adverse events, laboratory parameters, vital signs.
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

Brief 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. 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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Colorectal Cancer

Intervention

• 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 Name: 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 Name: Xeloda

Study Arms

• 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.
  Interventions:

  • Drug: Bevacizumab
  • Drug: Capecitabine
• Active Comparator: Capecitabine
  Participants received capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.
  Intervention: Drug: Capecitabine

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 28, 2014): 280
• Original Enrollment: Not Provided
• Actual Study Completion Date: March 2013
• Actual Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 70 Years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, Canada, Greece, Hungary, Italy, Korea, Republic of, Mexico, Netherlands, Poland, Slovenia, Spain, United Kingdom

Administrative Information

• NCT Number: NCT00484939
• Other Study ID Numbers: MO19286
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Not Provided
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: January 2015