A Study of Avastin (Bevacizumab) in Combination With XELOX in Patients With Metastatic Colorectal Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00700570
First received: June 17, 2008
Last updated: July 1, 2016
Last verified: July 2016
  Purpose
This single arm study will assess the resection rate of liver metastasis, time to disease progression, and safety of neoadjuvant treatment with Avastin in combination with oxaliplatin and capecitabine (XELOX) in patients with metastatic colorectal cancer with unresectable liver metastasis. Patients will receive Avastin 5mg/kg iv on day 1 of every 2 week cycle, oxaliplatin 85mg/m2 iv on day 1 of every 2 week cycle, and capecitabine 1000mg/m2 on days 1-5 and 8-12 of every 2 week cycle. The anticipated time on study treatment is 3-12 months, and the target sample size is <100 individuals.

Condition Intervention Phase
Colorectal Cancer
Drug: bevacizumab [Avastin]
Drug: capecitabine [Xeloda]
Drug: oxaliplatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label Study to Assess the Resection Rate of Liver Metastases Following Neoadjuvant Therapy With Avastin in Combination With Oxaliplatin and Capecitabine (XELOX) in Patients With Metastatic Colorectal Cancer With Unresectable Liver Metastasis

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With Conversion From Unresectable to Resectable Liver Metastases [ Time Frame: After 5 cycles of neoadjuvant treatment (10 weeks) ] [ Designated as safety issue: No ]
    Participants were assessed via microscopic and macroscopic examination for tumor resectability after completion of 5 cycles of neoadjuvant treatment. Unresectable participants exhibited any of the following criteria: greater than or equal to (≥) 4 liver metastases; location and/or distribution of metastatic disease within the liver considered unsuitable for resection with clear margins; liver involvement precluding resection, in the setting of adequate parenchymal volume for otherwise viable liver function in the immediate postoperative period; and inability to maintain adequate circulation for viable liver function. Participants who had not met any of the above criteria at the end of 5 cycles underwent surgical resection. The percentage of participants with conversion from initially unresectable to resectable liver metastases was calculated as [number of participants eligible for surgical resection divided by the number analyzed] multiplied by 100.


Secondary Outcome Measures:
  • Percentage of Participants With Disease Progression [ Time Frame: Up to approximately 3 years (at Baseline, end of Cycle 5, time of surgery, and within 4 weeks of end of treatment [EOT]) ] [ Designated as safety issue: No ]
    Objective tumor response was assessed using RECIST version 1.1. Disease progression was defined as a ≥20 percent (%) increase in the sum of longest diameters of target lesions, taking as reference the smallest sum obtained at previous tumor assessment, or the appearance of any new lesions. The percentage of participants with disease progression was calculated as [number of participants meeting the above criteria divided by the number analyzed] multiplied by 100.

  • Time to Disease Progression [ Time Frame: Up to approximately 3 years (at Baseline, end of Cycle 5, time of surgery, and within 4 weeks of EOT) ] [ Designated as safety issue: No ]
    Objective tumor response was assessed using RECIST version 1.1. Disease progression was defined as a ≥20% increase in the sum of longest diameters of target lesions, taking as reference the smallest sum obtained at previous tumor assessment, or the appearance of any new lesions. Time to disease progression was defined as the time from first dose to time of disease progression. Participants without progression were censored at the time of last tumor assessment. Time to disease progression was estimated using Kaplan-Meier analysis and expressed in months.

  • Percentage of Participants With a Best Overall Tumor Response of Complete Response (CR) or PR According to RECIST Version 1.1 [ Time Frame: Up to approximately 3 years (at Baseline, end of Cycle 5, time of surgery, within 4 weeks of EOT, and at least 4 weeks after initial response) ] [ Designated as safety issue: No ]
    Objective tumor response was assessed using RECIST version 1.1. CR was defined as the disappearance of all target lesions, and PR was defined as a ≥30% decrease in the sum of longest diameters compared to Baseline. Response was confirmed at a minimum of 4 weeks after the first documented response. The percentage of participants with confirmed CR or PR was calculated as [number of participants meeting the respective criteria divided by the number analyzed] multiplied by 100.

  • Percentage of Participants by Best Overall Tumor Response According to RECIST Version 1.1 [ Time Frame: Up to approximately 3 years (at Baseline, end of Cycle 5, time of surgery, within 4 weeks of EOT, and at least 4 weeks after initial response) ] [ Designated as safety issue: No ]
    Objective tumor response was assessed using RECIST version 1.1. CR was defined as the disappearance of all target lesions, and PR was defined as a ≥30% decrease in the sum of longest diameters compared to Baseline. Response was to be confirmed at a minimum of 4 weeks after the first documented response. Stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, as well as no new target lesions. Disease progression or PD was defined as a ≥20% increase in the sum of longest diameters of target lesions, taking as reference the smallest sum obtained at previous tumor assessment, or the appearance of any new lesions. Non-evaluability for tumor assessment was also documented when applicable. The percentage of participants with each level of response was calculated as [number of participants meeting the respective criteria divided by the number analyzed] multiplied by 100.


Enrollment: 45
Study Start Date: August 2008
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: bevacizumab [Avastin]
5mg/kg iv on day 1 of each 2 week cycle.
Drug: capecitabine [Xeloda]
1000mg/m2 iv on days 1-5 and 8-12 of each 2 week cycle
Drug: oxaliplatin
85mg/m2 iv on day 1 of each 2 week cycle

  Eligibility

Ages Eligible for Study:   up to 75 Years   (Child, Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • adult patients, <=75 years of age;
  • chemotherapy-naive for stage IV colorectal cancer with unresectable liver metastasis;
  • >=1 measurable lesion;
  • ECOG status 0-2.

Exclusion Criteria:

  • prior exposure to Avastin;
  • clinical or radiological evidence of CNS metastases;
  • uncontrolled hypertension, or clinically significant cardiovascular disease;
  • ongoing treatment with aspirin (>325mg/day) or other medications known to predispose to gastrointestinal ulceration.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00700570

Locations
Taiwan
Kaohsiung, Taiwan, 00833
Kaohsiung, Taiwan, 807
Taichung, Taiwan, 407
Taipei, Taiwan, 00112
Taipei, Taiwan, 112
Taoyuan County, Taiwan, 333
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00700570     History of Changes
Other Study ID Numbers: ML21209 
Study First Received: June 17, 2008
Results First Received: August 19, 2015
Last Updated: July 1, 2016
Health Authority: Taiwan: Department of Health

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Bevacizumab
Oxaliplatin
Capecitabine
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 28, 2016