Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 92 of 978 for:    colon cancer AND resection

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00700570
Recruitment Status : Completed
First Posted : June 18, 2008
Results First Posted : October 1, 2015
Last Update Posted : November 2, 2016
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Colorectal Cancer
Interventions Drug: bevacizumab [Avastin]
Drug: capecitabine [Xeloda]
Drug: oxaliplatin
Enrollment 45
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Resected Unresected
Hide Arm/Group Description Participants with unresectable liver metastases secondary to colorectal cancer (CRC) were assigned to receive neoadjuvant treatment of intravenous (IV) bevacizumab with oral (PO) capecitabine and IV oxaliplatin (XELOX). Bevacizumab was given as 5 milligrams per kilogram (mg/kg) on Day 1 of each 14-day cycle during Cycles 1 to 5 and/or Cycles 8 to 12. During Cycles 1 to 12, IV oxaliplatin was given as 85 milligrams per meter-squared (mg/m^2) on Day 1, and PO capecitabine as 1000 mg/m^2 twice daily on Days 1 to 5 and 8 to 12. Resectability was assessed at completion of Cycle 5. Resectable participants followed a new algorithm: complete Cycle 6 (XELOX), rest for 4 weeks, undergo surgery, rest for 4 weeks, complete adjuvant therapy during Cycles 7 (XELOX) and 8 to 12 (bevacizumab plus XELOX), and continue an additional 6 cycles with capecitabine and bevacizumab per Investigator discretion. Participants could be withdrawn at any point for unacceptable toxicity. Participants with unresectable liver metastases secondary to CRC were assigned to receive neoadjuvant treatment of IV bevacizumab with XELOX. Bevacizumab was given as 5 mg/kg on Day 1 of each 14-day cycle during Cycles 1 to 5 and/or Cycles 8 to 12. During Cycles 1 to 12, IV oxaliplatin was given as 85 mg/m^2 on Day 1, and PO capecitabine as 1000 mg/m^2 twice daily on Days 1 to 5 and 8 to 12. Resectability was assessed at completion of Cycle 5. Unresectable participants with partial response (PR) or stable disease (SD), according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, repeated neoadjuvant treatment until documented resectability or progressive disease (PD). Participants could be withdrawn at any point for unacceptable toxicity.
Period Title: Overall Study
Started 19 26
Completed 8 0
Not Completed 11 26
Reason Not Completed
Adverse Event             2             6
Discretion of Investigator or Sponsor             0             3
Disease Progression             8             11
Withdrawal by Subject             1             6
Arm/Group Title Resected Unresected Total
Hide Arm/Group Description Participants with unresectable liver metastases secondary to CRC were assigned to receive neoadjuvant treatment of IV bevacizumab with XELOX. Bevacizumab was given as 5 mg/kg on Day 1 of each 14-day cycle during Cycles 1 to 5 and/or Cycles 8 to 12. During Cycles 1 to 12, IV oxaliplatin was given as 85 mg/m^2 on Day 1, and PO capecitabine as 1000 mg/m^2 twice daily on Days 1 to 5 and 8 to 12. Resectability was assessed at completion of Cycle 5. Resectable participants followed a new algorithm: complete Cycle 6 (XELOX), rest for 4 weeks, undergo surgery, rest for 4 weeks, complete adjuvant therapy during Cycles 7 (XELOX) and 8 to 12 (bevacizumab plus XELOX), and continue an additional 6 cycles with capecitabine and bevacizumab per Investigator discretion. Participants could be withdrawn at any point for unacceptable toxicity. Participants with unresectable liver metastases secondary to CRC were assigned to receive neoadjuvant treatment of IV bevacizumab with XELOX. Bevacizumab was given as 5 mg/kg on Day 1 of each 14-day cycle during Cycles 1 to 5 and/or Cycles 8 to 12. During Cycles 1 to 12, IV oxaliplatin was given as 85 mg/m^2 on Day 1, and PO capecitabine as 1000 mg/m^2 twice daily on Days 1 to 5 and 8 to 12. Resectability was assessed at completion of Cycle 5. Unresectable participants with PR or SD, according to RECIST version 1.1, repeated neoadjuvant treatment until documented resectability or PD. Participants could be withdrawn at any point for unacceptable toxicity. Total of all reporting groups
Overall Number of Baseline Participants 19 26 45
Hide Baseline Analysis Population Description
Intent-to-Treat (ITT) Population: All enrolled participants who received at least one dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 19 participants 26 participants 45 participants
55.0  (11.6) 55.1  (10.4) 55.08  (11.2)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 26 participants 45 participants
Female
6
  31.6%
12
  46.2%
18
  40.0%
Male
13
  68.4%
14
  53.8%
27
  60.0%
1.Primary Outcome
Title Percentage of Participants With Conversion From Unresectable to Resectable Liver Metastases
Hide Description 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.
Time Frame After 5 cycles of neoadjuvant treatment (10 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population.
Arm/Group Title All Participants
Hide Arm/Group Description:
Participants with unresectable liver metastases secondary to CRC were assigned to receive neoadjuvant treatment of IV bevacizumab with XELOX. Bevacizumab was given as 5 mg/kg on Day 1 of each 14-day cycle during Cycles 1 to 5 and/or Cycles 8 to 12. During Cycles 1 to 12, IV oxaliplatin was given as 85 mg/m^2 on Day 1, and PO capecitabine as 1000 mg/m^2 twice daily on Days 1 to 5 and 8 to 12. Resectability was assessed at completion of Cycle 5. Resectable participants followed a new algorithm: complete Cycle 6 (XELOX), rest for 4 weeks, undergo surgery, rest for 4 weeks, complete adjuvant therapy during Cycles 7 (XELOX) and 8 to 12 (bevacizumab plus XELOX), and continue an additional 6 cycles with capecitabine and bevacizumab per Investigator discretion. Unresectable participants with PR or SD, according to RECIST version 1.1, repeated neoadjuvant treatment until documented resectability or PD. Participants could be withdrawn at any point for unacceptable toxicity.
Overall Number of Participants Analyzed 45
Measure Type: Number
Unit of Measure: percentage of participants
42.2
2.Secondary Outcome
Title Percentage of Participants With Disease Progression
Hide Description 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 Frame Up to approximately 3 years (at Baseline, end of Cycle 5, time of surgery, and within 4 weeks of end of treatment [EOT])
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population.
Arm/Group Title Resected Unresected
Hide Arm/Group Description:
Participants with unresectable liver metastases secondary to CRC were assigned to receive neoadjuvant treatment of IV bevacizumab with XELOX. Bevacizumab was given as 5 mg/kg on Day 1 of each 14-day cycle during Cycles 1 to 5 and/or Cycles 8 to 12. During Cycles 1 to 12, IV oxaliplatin was given as 85 mg/m^2 on Day 1, and PO capecitabine as 1000 mg/m^2 twice daily on Days 1 to 5 and 8 to 12. Resectability was assessed at completion of Cycle 5. Resectable participants followed a new algorithm: complete Cycle 6 (XELOX), rest for 4 weeks, undergo surgery, rest for 4 weeks, complete adjuvant therapy during Cycles 7 (XELOX) and 8 to 12 (bevacizumab plus XELOX), and continue an additional 6 cycles with capecitabine and bevacizumab per Investigator discretion. Participants could be withdrawn at any point for unacceptable toxicity.
Participants with unresectable liver metastases secondary to CRC were assigned to receive neoadjuvant treatment of IV bevacizumab with XELOX. Bevacizumab was given as 5 mg/kg on Day 1 of each 14-day cycle during Cycles 1 to 5 and/or Cycles 8 to 12. During Cycles 1 to 12, IV oxaliplatin was given as 85 mg/m^2 on Day 1, and PO capecitabine as 1000 mg/m^2 twice daily on Days 1 to 5 and 8 to 12. Resectability was assessed at completion of Cycle 5. Unresectable participants with PR or SD, according to RECIST version 1.1, repeated neoadjuvant treatment until documented resectability or PD. Participants could be withdrawn at any point for unacceptable toxicity.
Overall Number of Participants Analyzed 19 26
Measure Type: Number
Unit of Measure: percentage of participants
52.6 46.2
3.Secondary Outcome
Title Time to Disease Progression
Hide Description 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.
Time Frame Up to approximately 3 years (at Baseline, end of Cycle 5, time of surgery, and within 4 weeks of EOT)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population.
Arm/Group Title Resected Unresected
Hide Arm/Group Description:
Participants with unresectable liver metastases secondary to CRC were assigned to receive neoadjuvant treatment of IV bevacizumab with XELOX. Bevacizumab was given as 5 mg/kg on Day 1 of each 14-day cycle during Cycles 1 to 5 and/or Cycles 8 to 12. During Cycles 1 to 12, IV oxaliplatin was given as 85 mg/m^2 on Day 1, and PO capecitabine as 1000 mg/m^2 twice daily on Days 1 to 5 and 8 to 12. Resectability was assessed at completion of Cycle 5. Resectable participants followed a new algorithm: complete Cycle 6 (XELOX), rest for 4 weeks, undergo surgery, rest for 4 weeks, complete adjuvant therapy during Cycles 7 (XELOX) and 8 to 12 (bevacizumab plus XELOX), and continue an additional 6 cycles with capecitabine and bevacizumab per Investigator discretion. Participants could be withdrawn at any point for unacceptable toxicity.
Participants with unresectable liver metastases secondary to CRC were assigned to receive neoadjuvant treatment of IV bevacizumab with XELOX. Bevacizumab was given as 5 mg/kg on Day 1 of each 14-day cycle during Cycles 1 to 5 and/or Cycles 8 to 12. During Cycles 1 to 12, IV oxaliplatin was given as 85 mg/m^2 on Day 1, and PO capecitabine as 1000 mg/m^2 twice daily on Days 1 to 5 and 8 to 12. Resectability was assessed at completion of Cycle 5. Unresectable participants with PR or SD, according to RECIST version 1.1, repeated neoadjuvant treatment until documented resectability or PD. Participants could be withdrawn at any point for unacceptable toxicity.
Overall Number of Participants Analyzed 19 26
Median (95% Confidence Interval)
Unit of Measure: months
10.1
(7.0 to 20.4)
8.7
(5.0 to 14.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Resected, Unresected
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1341
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants With a Best Overall Tumor Response of Complete Response (CR) or PR According to RECIST Version 1.1
Hide Description 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.
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)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population.
Arm/Group Title Resected Unresected
Hide Arm/Group Description:
Participants with unresectable liver metastases secondary to CRC were assigned to receive neoadjuvant treatment of IV bevacizumab with XELOX. Bevacizumab was given as 5 mg/kg on Day 1 of each 14-day cycle during Cycles 1 to 5 and/or Cycles 8 to 12. During Cycles 1 to 12, IV oxaliplatin was given as 85 mg/m^2 on Day 1, and PO capecitabine as 1000 mg/m^2 twice daily on Days 1 to 5 and 8 to 12. Resectability was assessed at completion of Cycle 5. Resectable participants followed a new algorithm: complete Cycle 6 (XELOX), rest for 4 weeks, undergo surgery, rest for 4 weeks, complete adjuvant therapy during Cycles 7 (XELOX) and 8 to 12 (bevacizumab plus XELOX), and continue an additional 6 cycles with capecitabine and bevacizumab per Investigator discretion. Participants could be withdrawn at any point for unacceptable toxicity.
Participants with unresectable liver metastases secondary to CRC were assigned to receive neoadjuvant treatment of IV bevacizumab with XELOX. Bevacizumab was given as 5 mg/kg on Day 1 of each 14-day cycle during Cycles 1 to 5 and/or Cycles 8 to 12. During Cycles 1 to 12, IV oxaliplatin was given as 85 mg/m^2 on Day 1, and PO capecitabine as 1000 mg/m^2 twice daily on Days 1 to 5 and 8 to 12. Resectability was assessed at completion of Cycle 5. Unresectable participants with PR or SD, according to RECIST version 1.1, repeated neoadjuvant treatment until documented resectability or PD. Participants could be withdrawn at any point for unacceptable toxicity.
Overall Number of Participants Analyzed 19 26
Measure Type: Number
Unit of Measure: percentage of participants
47.4 34.6
5.Secondary Outcome
Title Percentage of Participants by Best Overall Tumor Response According to RECIST Version 1.1
Hide Description 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.
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)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population.
Arm/Group Title Resected Unresected
Hide Arm/Group Description:
Participants with unresectable liver metastases secondary to CRC were assigned to receive neoadjuvant treatment of IV bevacizumab with XELOX. Bevacizumab was given as 5 mg/kg on Day 1 of each 14-day cycle during Cycles 1 to 5 and/or Cycles 8 to 12. During Cycles 1 to 12, IV oxaliplatin was given as 85 mg/m^2 on Day 1, and PO capecitabine as 1000 mg/m^2 twice daily on Days 1 to 5 and 8 to 12. Resectability was assessed at completion of Cycle 5. Resectable participants followed a new algorithm: complete Cycle 6 (XELOX), rest for 4 weeks, undergo surgery, rest for 4 weeks, complete adjuvant therapy during Cycles 7 (XELOX) and 8 to 12 (bevacizumab plus XELOX), and continue an additional 6 cycles with capecitabine and bevacizumab per Investigator discretion. Participants could be withdrawn at any point for unacceptable toxicity.
Participants with unresectable liver metastases secondary to CRC were assigned to receive neoadjuvant treatment of IV bevacizumab with XELOX. Bevacizumab was given as 5 mg/kg on Day 1 of each 14-day cycle during Cycles 1 to 5 and/or Cycles 8 to 12. During Cycles 1 to 12, IV oxaliplatin was given as 85 mg/m^2 on Day 1, and PO capecitabine as 1000 mg/m^2 twice daily on Days 1 to 5 and 8 to 12. Resectability was assessed at completion of Cycle 5. Unresectable participants with PR or SD, according to RECIST version 1.1, repeated neoadjuvant treatment until documented resectability or PD. Participants could be withdrawn at any point for unacceptable toxicity.
Overall Number of Participants Analyzed 19 26
Measure Type: Number
Unit of Measure: percentage of participants
CR 36.8 0
PR 10.5 34.6
SD 0 15.4
PD 52.6 46.2
Non-evaluable 0 3.8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Resected, Unresected
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0010
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Time Frame Up to approximately 3 years (continuously until 4 weeks after EOT)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title All Participants
Hide Arm/Group Description Participants with unresectable liver metastases secondary to CRC were assigned to receive neoadjuvant treatment of IV bevacizumab with XELOX. Bevacizumab was given as 5 mg/kg on Day 1 of each 14-day cycle during Cycles 1 to 5 and/or Cycles 8 to 12. During Cycles 1 to 12, IV oxaliplatin was given as 85 mg/m^2 on Day 1, and PO capecitabine as 1000 mg/m^2 twice daily on Days 1 to 5 and 8 to 12. Resectability was assessed at completion of Cycle 5. Resectable participants followed a new algorithm: complete Cycle 6 (XELOX), rest for 4 weeks, undergo surgery, rest for 4 weeks, complete adjuvant therapy during Cycles 7 (XELOX) and 8 to 12 (bevacizumab plus XELOX), and continue an additional 6 cycles with capecitabine and bevacizumab per Investigator discretion. Unresectable participants with PR or SD, according to RECIST version 1.1, repeated neoadjuvant treatment until documented resectability or PD. Participants could be withdrawn at any point for unacceptable toxicity.
All-Cause Mortality
All Participants
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
All Participants
Affected / at Risk (%)
Total   11/45 (24.44%) 
Gastrointestinal disorders   
Diarrhoea * 1  3/45 (6.67%) 
Enteritis * 1  1/45 (2.22%) 
Gastrointestinal haemorrhage * 1  1/45 (2.22%) 
Ileus * 1  2/45 (4.44%) 
General disorders   
Pyrexia * 1  2/45 (4.44%) 
Infections and infestations   
Enterocolitis infectious * 1  1/45 (2.22%) 
Perihepatic abscess * 1  1/45 (2.22%) 
Injury, poisoning and procedural complications   
Intestinal anastomosis complication * 1  1/45 (2.22%) 
Metabolism and nutrition disorders   
Hypoglycaemia * 1  1/45 (2.22%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Tumour associated fever * 1  1/45 (2.22%) 
Tumour necrosis * 1  1/45 (2.22%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (15.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
All Participants
Affected / at Risk (%)
Total   45/45 (100.00%) 
Blood and lymphatic system disorders   
Anaemia * 1  5/45 (11.11%) 
Leukopenia * 1  6/45 (13.33%) 
Neutropenia * 1  11/45 (24.44%) 
Thrombocytopenia * 1  19/45 (42.22%) 
Gastrointestinal disorders   
Abdominal pain * 1  8/45 (17.78%) 
Constipation * 1  5/45 (11.11%) 
Diarrhoea * 1  16/45 (35.56%) 
Nausea * 1  14/45 (31.11%) 
Stomatitis * 1  7/45 (15.56%) 
Vomiting * 1  17/45 (37.78%) 
General disorders   
Fatigue * 1  18/45 (40.00%) 
Mucosal inflammation * 1  8/45 (17.78%) 
Pyrexia * 1  8/45 (17.78%) 
Infections and infestations   
Paronychia * 1  3/45 (6.67%) 
Urinary tract infection * 1  3/45 (6.67%) 
Investigations   
Weight decreased * 1  4/45 (8.89%) 
Metabolism and nutrition disorders   
Decreased appetite * 1  20/45 (44.44%) 
Nervous system disorders   
Dizziness * 1  3/45 (6.67%) 
Hypoaesthesia * 1  3/45 (6.67%) 
Neuropathy peripheral * 1  19/45 (42.22%) 
Peripheral sensory neuropathy * 1  9/45 (20.00%) 
Psychiatric disorders   
Insomnia * 1  9/45 (20.00%) 
Renal and urinary disorders   
Proteinuria * 1  15/45 (33.33%) 
Respiratory, thoracic and mediastinal disorders   
Epistaxis * 1  4/45 (8.89%) 
Hiccups * 1  5/45 (11.11%) 
Skin and subcutaneous tissue disorders   
Palmar-plantar erythrodysaesthesia syndrome * 1  35/45 (77.78%) 
Pigmentation disorder * 1  4/45 (8.89%) 
Rash * 1  4/45 (8.89%) 
Vascular disorders   
Hypertension * 1  8/45 (17.78%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (15.1)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Name/Title: Medical Communications
Organization: Hoffmann-LaRoche
Phone: 800-821-8590
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00700570     History of Changes
Other Study ID Numbers: ML21209
First Submitted: June 17, 2008
First Posted: June 18, 2008
Results First Submitted: August 19, 2015
Results First Posted: October 1, 2015
Last Update Posted: November 2, 2016