Comparison of Combination Chemotherapy Regimens With or Without Cetuximab in Treating Patients Who Have Undergone Surgery For Stage III Colon Cancer

This study has been completed.
Sponsor:
Collaborator:
Eastern Cooperative Oncology Group
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00079274
First received: March 8, 2004
Last updated: January 23, 2015
Last verified: October 2014
Results First Received: December 5, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Adenocarcinoma of the Colon
Stage III Colon Cancer
Interventions: Drug: irinotecan hydrochloride
Drug: oxaliplatin
Drug: leucovorin calcium
Drug: fluorouracil
Biological: cetuximab
Drug: Locally Directed Therapy

  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
No text entered.

Reporting Groups
  Description
Arm A (Combination Chemotherapy)

Patients received oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46-48 hours on days 1. Treatment repeated every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease.

oxaliplatin: Given IV

leucovorin calcium: Given IV

fluorouracil: Given IV

Arm B (Combination Chemotherapy)

Patients received irinotecan IV over 2 hours on day 1 and leucovorin calcium and fluorouracil as in arm A. Treatment repeated every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease.

irinotecan hydrochloride: Given IV

leucovorin calcium: Given IV

fluorouracil: Given IV

Arm C (Combination Chemotherapy)

Patients received the same treatment as in arm A for 6 courses followed by the same treatment as in arm B for 6 courses (total of 12 courses). Treatment continues in the absence of unacceptable toxicity or recurrent disease.

irinotecan hydrochloride: Given IV

oxaliplatin: Given IV

leucovorin calcium: Given IV

fluorouracil: Given IV

Arm D (Combination Chemotherapy, Monoclonal Antibody)

Patients received cetuximab IV over 1 hour on days 1 and 8 and oxaliplatin, leucovorin calcium, and fluorouracil as in arm A. Treatment repeated every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease.

oxaliplatin: Given IV

leucovorin calcium: Given IV

fluorouracil: Given IV

cetuximab: Given IV

Arm E (Combination Chemotherapy, Monoclonal Antibody)

Patients received cetuximab as in arm D and irinotecan, leucovorin calcium, and fluorouracil as in arm B. Treatment repeated every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease.

irinotecan hydrochloride: Given IV

leucovorin calcium: Given IV

fluorouracil: Given I

cetuximab: Given IV

Arm F (Combination Chemotherapy, Monoclonal Antibody)

Patients received cetuximab as in arm D and chemotherapy as in arm C.

irinotecan hydrochloride: Given IV

oxaliplatin: Given IV

leucovorin calcium: Given IV

fluorouracil: Given IV

cetuximab: Given IV

Arm G (Locally Directed Therapy)

Patients determined to have mutated Kirsten rat sarcoma (KRAS) (or KRAS not evaluable) were assigned to an event monitoring arm in which adjuvant therapy was determined and assigned by the treating oncologist. The determination of the type of therapy, duration of treatment, and dose modification was the responsibility of the treating oncologists.

Locally Directed Therapy: Patients determined to have mutated KRAS (or KRAS not evaluable) were assigned to an event monitoring arm in which adjuvant therapy was determined and assigned by the treating oncologist. The determination of the type of therapy, duration of treatment, and dose modification was the responsibility of the treating oncologists.


Participant Flow:   Overall Study
    Arm A (Combination Chemotherapy)     Arm B (Combination Chemotherapy)     Arm C (Combination Chemotherapy)     Arm D (Combination Chemotherapy, Monoclonal Antibody)     Arm E (Combination Chemotherapy, Monoclonal Antibody)     Arm F (Combination Chemotherapy, Monoclonal Antibody)     Arm G (Locally Directed Therapy)  
STARTED     1402     111     111     1350     45     46     332  
COMPLETED     1081     84     84     906     30     26     332  
NOT COMPLETED     321     27     27     444     15     20     0  
Withdrawal by Subject                 111                 10                 12                 163                 7                 8                 0  
Adverse Event                 130                 8                 8                 184                 7                 8                 0  
Recurrence                 21                 0                 1                 15                 0                 2                 0  
Alternate Treatment                 6                 1                 0                 3                 0                 0                 0  
Other Medical Problems                 6                 1                 0                 7                 0                 0                 0  
Death                 4                 0                 1                 15                 0                 0                 0  
Cytogenetic resistance                 0                 0                 0                 2                 0                 0                 0  
Not Specified                 43                 7                 5                 55                 1                 2                 0  



  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.
No text entered.

Reporting Groups
  Description
Arm A (Combination Chemotherapy)

Patients received oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46-48 hours on days 1. Treatment repeated every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease.

oxaliplatin: Given IV

leucovorin calcium: Given IV

fluorouracil: Given IV

Arm B (Combination Chemotherapy)

Patients received irinotecan IV over 2 hours on day 1 and leucovorin calcium and fluorouracil as in arm A. Treatment repeated every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease.

irinotecan hydrochloride: Given IV

leucovorin calcium: Given IV

fluorouracil: Given IV

Arm C (Combination Chemotherapy)

Patients received the same treatment as in arm A for 6 courses followed by the same treatment as in arm B for 6 courses (total of 12 courses). Treatment continues in the absence of unacceptable toxicity or recurrent disease.

irinotecan hydrochloride: Given IV

oxaliplatin: Given IV

leucovorin calcium: Given IV

fluorouracil: Given IV

Arm D (Combination Chemotherapy, Monoclonal Antibody)

Patients received cetuximab IV over 1 hour on days 1 and 8 and oxaliplatin, leucovorin calcium, and fluorouracil as in arm A. Treatment repeated every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease.

oxaliplatin: Given IV

leucovorin calcium: Given IV

fluorouracil: Given IV

cetuximab: Given IV

Arm E (Combination Chemotherapy, Monoclonal Antibody)

Patients received cetuximab as in arm D and irinotecan, leucovorin calcium, and fluorouracil as in arm B. Treatment repeated every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease.

irinotecan hydrochloride: Given IV

leucovorin calcium: Given IV

fluorouracil: Given IV

cetuximab: Given IV

Arm F (Combination Chemotherapy, Monoclonal Antibody)

Patients received cetuximab as in arm D and chemotherapy as in arm C.

irinotecan hydrochloride: Given IV

oxaliplatin: Given IV

leucovorin calcium: Given IV

fluorouracil: Given IV

cetuximab: Given IV

Arm G (Locally Directed Therapy)

Patients determined to have mutated KRAS (or KRAS not evaluable) were assigned to an event monitoring arm in which adjuvant therapy was determined and assigned by the treating oncologist. The determination of the type of therapy, duration of treatment, and dose modification was the responsibility of the treating oncologists.

Locally Directed Therapy: Patients determined to have mutated KRAS (or KRAS not evaluable) were assigned to an event monitoring arm in which adjuvant therapy was determined and assigned by the treating oncologist. The determination of the type of therapy, duration of treatment, and dose modification was the responsibility of the treating oncologists.

Total Total of all reporting groups

Baseline Measures
    Arm A (Combination Chemotherapy)     Arm B (Combination Chemotherapy)     Arm C (Combination Chemotherapy)     Arm D (Combination Chemotherapy, Monoclonal Antibody)     Arm E (Combination Chemotherapy, Monoclonal Antibody)     Arm F (Combination Chemotherapy, Monoclonal Antibody)     Arm G (Locally Directed Therapy)     Total  
Number of Participants  
[units: participants]
  1402     111     111     1350     45     46     332     3397  
Age  
[units: years]
Median (Full Range)
  58   (19 to 85)     57   (25 to 82)     60   (24 to 82)     58   (22 to 86)     59   (30 to 82)     60.5   (30 to 81)     56   (22 to 84)     58   (19 to 86)  
Gender  
[units: participants]
               
Female     662     53     50     647     20     21     160     1613  
Male     740     58     61     703     25     25     172     1784  
Ethnicity (NIH/OMB)  
[units: participants]
               
Hispanic or Latino     64     5     3     62     4     2     18     158  
Not Hispanic or Latino     1107     103     103     1060     38     41     225     2677  
Unknown or Not Reported     231     3     5     228     3     3     89     562  
Race (NIH/OMB)  
[units: participants]
               
American Indian or Alaska Native     6     1     1     7     0     0     1     16  
Asian     66     4     2     62     3     0     12     149  
Native Hawaiian or Other Pacific Islander     8     0     1     7     0     0     0     16  
Black or African American     94     6     7     96     5     2     29     239  
White     1202     98     100     1154     37     43     275     2909  
More than one race     3     2     0     3     0     0     1     9  
Unknown or Not Reported     23     0     0     21     0     1     14     59  
Region of Enrollment  
[units: participants]
               
United States     1258     109     109     1224     44     46     303     3093  
Canada     138     2     2     124     1     0     28     295  
Jamaica     1     0     0     0     0     0     0     1  
Puerto Rico     5     0     0     2     0     0     1     8  
Positive Nodes [1]
[units: participants]
               
1-3     816     71     70     790     29     28     203     2007  
4+     586     40     41     560     16     18     129     1390  
Tumor Stage [2]
[units: participants]
               
T1 or T2     198     18     14     213     5     5     56     509  
T3     1046     78     93     983     35     39     214     2488  
T4     158     15     4     153     4     2     62     398  
Not Availabe     0     0     0     1     1     0     0     2  
Histologic Grade [3]
[units: participants]
               
High     357     25     28     345     10     12     60     837  
Low     1045     86     83     1005     35     34     272     2560  
KRAS Status  
[units: participants]
               
Unknown     56     6     6     51     3     4     6     132  
Mutant     391     33     43     345     15     13     326     1166  
Wildtype     955     72     62     954     27     29     0     2099  
[1] Number of positive nodes
[2]

T1: Tumor invades submucosa

T2: Tumor invades muscularis propria

T3: Tumor invades through the muscularis propria into the subserosa or into non-peritonealized pericolic or perirectal tissues

T4: (T4a+) Tumor perforates the visceral peritoneum without adherence to or invasion of other organs or structures or (T4b) Tumor is adherent to or directly invades other organs or structures

[3] High=poorly differentiated or undifferentiated > Low=well or moderately differentiated



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Disease-free Survival (Arms A and D: Wild-type KRAS Patients)   [ Time Frame: At 3 years ]

2.  Secondary:   Disease-free Survival (Arms A and D: Mutant KRAS Patients)   [ Time Frame: At 3 years ]

3.  Secondary:   Disease-free Survival   [ Time Frame: Up to 5 years ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No

4.  Secondary:   Overall Survival   [ Time Frame: Up to 8 years ]
Results not yet reported.   Anticipated Reporting Date:   01/2018   Safety Issue:   No

5.  Secondary:   Toxicity   [ Time Frame: Assessed up to 8 years ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   Yes


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
Accrual to arms A and D terminated early based on the results of the planned 2nd interim analysis. Sample sizes limit statistical conclusions for data from the irinotecan treated patients as those treatment arms were discontinued early in the study.


  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 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.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Dr. Steven Alberts
Organization: North Central Cancer Treatment Group
phone: 507-284-8432
e-mail: alberts.steven@mayo.edu


No publications provided by National Cancer Institute (NCI)

Publications automatically indexed to this study:

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00079274     History of Changes
Obsolete Identifiers: NCT00170092
Other Study ID Numbers: NCI-2009-00639, N0147, U10CA025224, CDR0000355132
Study First Received: March 8, 2004
Results First Received: December 5, 2013
Last Updated: January 23, 2015
Health Authority: United States: Food and Drug Administration