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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 
Overall Participants Analyzed 
[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 
[1] Number of positive nodes
Tumor Stage [1] 
[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 
[1]

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

Histologic Grade [1] 
[Units: Participants]
               
High   357   25   28   345   10   12   60   837 
Low   1045   86   83   1005   35   34   272   2560 
[1] High=poorly differentiated or undifferentiated > Low=well or moderately differentiated
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 


  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


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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 ( US NIH Grant/Contract Award Number )
CDR0000355132 ( Registry Identifier: PDQ (Physician Data Query) )
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