Combination Chemotherapy With or Without Bevacizumab in Treating Patients Who Have Undergone Surgery for High Risk Stage II or Stage III Colon Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00112918
First received: June 2, 2005
Last updated: June 19, 2013
Last verified: June 2013
Results First Received: June 1, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Colorectal Cancer
Interventions: Biological: Bevacizumab
Drug: Capecitabine
Drug: 5-Fluorouracil (5-FU)
Drug: Leucovorin calcium
Drug: Oxaliplatin

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Randomization was stratified according to geographic region and disease stage (high-risk stage II or stage III N1 or stage III N2). The primary analysis population consisted of patients with Stage III disease.

Reporting Groups
  Description
FOLFOX4

Weeks 1-24: Oxaliplatin was administered as an 85 mg/m^2 intravenous infusion over 2 hours concomitantly with leucovorin as a 200 mg/m^2 infusion over 2 hours, followed by 5-fluorouracil (5-FU), given as a 400 mg/m^2 bolus injection, and then as a 600 mg/m^2 continuous infusion over 22 hours. Leucovorin 200 mg/m^2 (alone), followed by 5-FU 400 mg/m^2 bolus injection, and 5-FU 600 mg/m^2 continuous infusion were repeated on day 2. Cycle length was 2 weeks and cycles were repeated every second week for a total of 12 cycles (24 weeks).

Weeks 25-48: Observation only.

FOLFOX4 + Bv

Weeks 1-24: Bevacizumab 5 mg/kg was administered as an intravenous infusion over 30 - 90 minutes followed by oxaliplatin, administered as an 85 mg/m^2 intravenous infusion over 2 hours (on day 1 only) concomitantly with leucovorin, as a 200 mg/m^2 infusion over 2 hours, followed by 5-FU, given as a 400 mg/m^2 bolus injection, and then as a 600 mg/m^2 continuous infusion over 22 hours. Leucovorin 200 mg/m^2 (alone), followed by 5-FU 400 mg/m^2 bolus injection, and 5-FU 600 mg/m^2 continuous infusion are repeated on day 2. Cycle length is 2 weeks and cycles were repeated every second week for a total of 12 cycles (24 weeks).

Weeks 25-48: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 minutes. Cycle length was 3 weeks. Cycles were repeated every 3 weeks for a total of 8 cycles (24 weeks).

XELOX+Bv

Weeks 1-24: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 - 90 minutes followed by oxaliplatin administered as a 130 mg/m^2 intravenous infusion over 2 hours (day 1 every 3 weeks) in combination with capecitabine, which was administered orally at a dose of 1000 mg/m^2 twice daily (equivalent to a total daily dose of 2000 mg/m^2), with first dose the evening of day 1 and last dose the morning of day 15, given as intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment), for a total of 8 cycles (24 weeks).

Weeks 25-48: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 minutes. Cycle length was 3 weeks. Cycles were repeated every 3 weeks for a total of 8 cycles (24 weeks).


Participant Flow:   Overall Study
    FOLFOX4     FOLFOX4 + Bv     XELOX+Bv  
STARTED     1151     1155     1145  
Received Treatment     1126     1145 [1]   1135  
Stage III Disease Population     955     960     952  
COMPLETED     854 [2]   810 [2]   846 [2]
NOT COMPLETED     297     345     299  
[1] Includes two patients from FOLFOX4 who received Bv and were assigned to FOLFOX4+Bv safety analysis
[2] Represents patients alive in follow-up at the time of final data cut-off (30 June 2012)



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Baseline Measures are based on the Intent-to-Treat - Stage III Disease Patient Population.

Reporting Groups
  Description
FOLFOX4

Weeks 1-24: Oxaliplatin was administered as an 85 mg/m^2 intravenous infusion over 2 hours concomitantly with leucovorin as a 200 mg/m^2 infusion over 2 hours, followed by 5-fluorouracil (5-FU), given as a 400 mg/m^2 bolus injection, and then as a 600 mg/m^2 continuous infusion over 22 hours. Leucovorin 200 mg/m^2 (alone), followed by 5-FU 400 mg/m^2 bolus injection, and 5-FU 600 mg/m^2 continuous infusion were repeated on day 2. Cycle length was 2 weeks and cycles were repeated every second week for a total of 12 cycles (24 weeks).

Weeks 25-48: Observation only.

FOLFOX4 + Bv

Weeks 1–24: Bevacizumab 5 mg/kg was administered as an intravenous infusion over 30 – 90 minutes followed by oxaliplatin, administered as an 85 mg/m^2 intravenous infusion over 2 hours (on day 1 only) concomitantly with leucovorin, as a 200 mg/m^2 infusion over 2 hours, followed by 5-FU, given as a 400 mg/m^2 bolus injection, and then as a 600 mg/m^2 continuous infusion over 22 hours. Leucovorin 200 mg/m^2 (alone), followed by 5-FU 400 mg/m^2 bolus injection, and 5-FU 600 mg/m^2 continuous infusion are repeated on day 2. Cycle length is 2 weeks and cycles were repeated every second week for a total of 12 cycles (24 weeks).

Weeks 25–48: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 minutes. Cycle length was 3 weeks. Cycles were repeated every 3 weeks for a total of 8 cycles (24 weeks).

XELOX+Bv

Weeks 1–24: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 – 90 minutes followed by oxaliplatin administered as a 130 mg/m^2 intravenous infusion over 2 hours (day 1 every 3 weeks) in combination with capecitabine, which was administered orally at a dose of 1000 mg/m^2 twice daily (equivalent to a total daily dose of 2000 mg/m^2), with first dose the evening of day 1 and last dose the morning of day 15, given as intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment), for a total of 8 cycles (24 weeks).

Weeks 25–48: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 minutes. Cycle length was 3 weeks. Cycles were repeated every 3 weeks for a total of 8 cycles (24 weeks).

Total Total of all reporting groups

Baseline Measures
    FOLFOX4     FOLFOX4 + Bv     XELOX+Bv     Total  
Number of Participants  
[units: participants]
  955     960     952     2867  
Age, Customized  
[units: participants]
       
<40     77     74     68     219  
40-65     603     625     588     1816  
>=65     275     261     296     832  
Gender  
[units: participants]
       
Female     425     473     432     1330  
Male     530     487     520     1537  
Race/Ethnicity, Customized  
[units: participants]
       
American Indian or Alaska Native     1     1     0     2  
Asian     139     115     123     377  
Black or African American     6     13     14     33  
White     791     813     795     2399  
Other     18     18     20     56  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Disease-free Survival in Stage III Cancer Patients - Time to Event   [ Time Frame: From first patient randomized until the data cut-off date of 30 June 2010 (36 months after the last patient randomized). ]

2.  Primary:   Disease-free Survival in Stage III Cancer Patients - Number of Events   [ Time Frame: From first patient randomized until the data cut-off date of 30 June 2010 (36 months after the last patient randomized). ]

3.  Secondary:   Overall Survival in Stage III Cancer Patients - Time to Event   [ Time Frame: From first patient randomized until the clinical data cut-off date of 30 June 2010 (36 months after the last patient randomized). ]
  Hide Outcome Measure 3

Measure Type Secondary
Measure Title Overall Survival in Stage III Cancer Patients - Time to Event
Measure Description Overall survival was defined as the time between date of randomization and date of death due to any cause. Patients not reported as having died at the time of the analysis were censored at the date they were last known to be alive.
Time Frame From first patient randomized until the clinical data cut-off date of 30 June 2010 (36 months after the last patient randomized).  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT patients with Stage III disease.

Reporting Groups
  Description
FOLFOX4

Weeks 1-24: Oxaliplatin was administered as an 85 mg/m^2 intravenous infusion over 2 hours concomitantly with leucovorin as a 200 mg/m^2 infusion over 2 hours, followed by 5-FU, given as a 400 mg/m^2 bolus injection, and then as a 600 mg/m^2 continuous infusion over 22 hours. Leucovorin 200 mg/m^2 (alone), followed by 5-FU 400 mg/m^2 bolus injection, and 5-FU 600 mg/m^2 continuous infusion were repeated on day 2. Cycle length was 2 weeks and cycles were repeated every second week for a total of 12 cycles (24 weeks).

Weeks 25-48: Observation only.

FOLFOX4 + Bv

Weeks 1-24: Bevacizumab 5 mg/kg was administered as an intravenous infusion over 30 - 90 minutes followed by oxaliplatin, administered as an 85 mg/m^2 intravenous infusion over 2 hours (on day 1 only) concomitantly with leucovorin, as a 200 mg/m^2 infusion over 2 hours, followed by 5-FU, given as a 400 mg/m^2 bolus injection, and then as a 600 mg/m^2 continuous infusion over 22 hours. Leucovorin 200 mg/m^2 (alone), followed by 5-FU 400 mg/m^2 bolus injection, and 5-FU 600 mg/m^2 continuous infusion are repeated on day 2. Cycle length is 2 weeks and cycles were repeated every second week for a total of 12 cycles (24 weeks).

Weeks 25-48: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 minutes. Cycle length was 3 weeks. Cycles were repeated every 3 weeks for a total of 8 cycles (24 weeks).

XELOX+Bv

Weeks 1-24: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 - 90 minutes followed by oxaliplatin administered as a 130 mg/m^2 intravenous infusion over 2 hours (day 1 every 3 weeks) in combination with capecitabine, which was administered orally at a dose of 1000 mg/m^2 twice daily (equivalent to a total daily dose of 2000 mg/m^2), with first dose the evening of day 1 and last dose the morning of day 15, given as intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment), for a total of 8 cycles (24 weeks).

Weeks 25-48: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 minutes. Cycle length was 3 weeks. Cycles were repeated every 3 weeks for a total of 8 cycles (24 weeks).


Measured Values
    FOLFOX4     FOLFOX4 + Bv     XELOX+Bv  
Number of Participants Analyzed  
[units: participants]
  955     960     952  
Overall Survival in Stage III Cancer Patients - Time to Event  
[units: months]
Median ( 95% Confidence Interval )
  NA  
  ( NA to NA ) [1]
  NA  
  ( NA to NA ) [1]
  NA  
  ( NA to NA ) [1]
[1] Median time to event and 95% confidence intervals could not be estimated due to the low number of events.

No statistical analysis provided for Overall Survival in Stage III Cancer Patients - Time to Event



4.  Secondary:   Overall Survival in Stage III Cancer Patients - Number of Events   [ Time Frame: From first patient randomized until the clinical data cut-off date of 30 June 2010 (36 months after the last patient randomized). ]

5.  Secondary:   Overall Survival in Stage III Cancer Patients - Time to Event: Final Analysis   [ Time Frame: From first patient randomized until the final data cut-off date of 30 June 2012 (5 years after the last patient randomized). ]

6.  Secondary:   Overall Survival in Stage III Cancer Patients - Number of Events: Final Analysis   [ Time Frame: From first patient randomized until the final data cut-off date of 30 June 2012 (5 years after the last patient randomized). ]
  Hide Outcome Measure 6

Measure Type Secondary
Measure Title Overall Survival in Stage III Cancer Patients - Number of Events: Final Analysis
Measure Description An overall survival event was death due to any cause.
Time Frame From first patient randomized until the final data cut-off date of 30 June 2012 (5 years after the last patient randomized).  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT patients with Stage III disease.

Reporting Groups
  Description
FOLFOX4

Weeks 1-24: Oxaliplatin was administered as an 85 mg/m^2 intravenous infusion over 2 hours concomitantly with leucovorin as a 200 mg/m^2 infusion over 2 hours, followed by 5-FU, given as a 400 mg/m^2 bolus injection, and then as a 600 mg/m^2 continuous infusion over 22 hours. Leucovorin 200 mg/m^2 (alone), followed by 5-FU 400 mg/m^2 bolus injection, and 5-FU 600 mg/m^2 continuous infusion were repeated on day 2. Cycle length was 2 weeks and cycles were repeated every second week for a total of 12 cycles (24 weeks).

Weeks 25-48: Observation only.

FOLFOX4 + Bv

Weeks 1-24: Bevacizumab 5 mg/kg was administered as an intravenous infusion over 30 - 90 minutes followed by oxaliplatin, administered as an 85 mg/m^2 intravenous infusion over 2 hours (on day 1 only) concomitantly with leucovorin, as a 200 mg/m^2 infusion over 2 hours, followed by 5-FU, given as a 400 mg/m^2 bolus injection, and then as a 600 mg/m^2 continuous infusion over 22 hours. Leucovorin 200 mg/m^2 (alone), followed by 5-FU 400 mg/m^2 bolus injection, and 5-FU 600 mg/m^2 continuous infusion are repeated on day 2. Cycle length is 2 weeks and cycles were repeated every second week for a total of 12 cycles (24 weeks).

Weeks 25-48: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 minutes. Cycle length was 3 weeks. Cycles were repeated every 3 weeks for a total of 8 cycles (24 weeks).

XELOX+Bv

Weeks 1-24: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 - 90 minutes followed by oxaliplatin administered as a 130 mg/m^2 intravenous infusion over 2 hours (day 1 every 3 weeks) in combination with capecitabine, which was administered orally at a dose of 1000 mg/m^2 twice daily (equivalent to a total daily dose of 2000 mg/m^2), with first dose the evening of day 1 and last dose the morning of day 15, given as intermittent treatment (3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment), for a total of 8 cycles (24 weeks).

Weeks 25-48: Bevacizumab 7.5 mg/kg was administered as an intravenous infusion over 30 minutes. Cycle length was 3 weeks. Cycles were repeated every 3 weeks for a total of 8 cycles (24 weeks).


Measured Values
    FOLFOX4     FOLFOX4 + Bv     XELOX+Bv  
Number of Participants Analyzed  
[units: participants]
  955     960     952  
Overall Survival in Stage III Cancer Patients - Number of Events: Final Analysis  
[units: participants]
     
Patients with events     161     202     182  
Patients without events     794     758     770  

No statistical analysis provided for Overall Survival in Stage III Cancer Patients - Number of Events: Final Analysis




  Serious Adverse Events


  Other Adverse Events


  More Information
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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 agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Medical Communications
Organization: Hoffman-LaRoche
phone: 800-821-8590


No publications provided by Hoffmann-La Roche

Publications automatically indexed to this study:

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00112918     History of Changes
Other Study ID Numbers: CDR0000427299, P30CA016042, UCLA-0412086-01, ROCHE-BO17920A
Study First Received: June 2, 2005
Results First Received: June 1, 2012
Last Updated: June 19, 2013
Health Authority: United States: Food and Drug Administration