NCT00079274

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

A Randomized Phase III Trial of Oxaliplatin (OXAL) Plus 5-Fluorouracil (5-FU)/Leucovorin (CF) With or Without Cetuximab (C225) After Curative Resection for Patients With Stage III Colon Cancer

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 3,397 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years – 99 Years
• Healthy volunteers: Not accepted

Summary

This randomized phase III trial was originally designed to compare three different combination chemotherapy regimens to see how well they work. As of September 1, 2004, the study was expanded to a total of 6 arms (the original 3 arms (A, B, C) and 3 additional arms which were the same as the first 3 but with cetuximab) in treating patients who have undergone surgery for stage III colon cancer. Drugs used in chemotherapy, such as irinotecan hydrochloride, fluorouracil, leucovorin calcium, and oxaliplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as cetuximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining more than one chemotherapy drug with monoclonal antibody therapy and giving them after surgery may kill any remaining tumor cells. It was not known at the time this study was developed which combination chemotherapy regimen is more effective after surgery in treating colon cancer. This study had several key changes, based on the results of other phase III trials. As of 6/1/2005, patients no longer received irinotecan on this study and treatment arms B, C, E, and F were discontinued. Patients on arms B and C crossed to arm A. Patients on arms E and F crossed to arm D. Patients on arms C and F who had not gotten to irinotecan continued on arms A and D, respectively. As of 8/18/2008, pre-screening for Kirsten rat sarcoma (KRAS) status was added with mutant KRAS (or KRAS not evaluable) patients put on arm G and wild-type KRAS patients randomized between arm A and arm D. Patients on arm G were treated per physician discretion and followed for disease and survival status. KRAS was determined in a central laboratory and was process for all patients on this study. The primary endpoint of this study was modified on 8/18/2008 to focus on patients having wild-type KRAS tumors. All modifications were approved by the Central Institution Review Board, local Institutional Review Boards, NCI, and the NCCTG Data Safety Monitoring Board.

Detailed description

PRIMARY OBJECTIVES: I. Disease-free Survival (Arms A and D: Wild-type KRAS Patients) SECONDARY OBJECTIVES: I. Disease-free Survival (Arms A and D: Mutant KRAS Patients) II. Disease-free Survival III. Overall Survival IV. Toxicity OUTLINE: This is a randomized, multicenter study. Patients are stratified according to positive lymph node involvement (1-3 vs 4 or more), histology (high \[poorly differentiated or undifferentiated\] vs low \[well to moderately differentiated\]), and clinical T stage (T1 or T2 vs T3 vs T4). Patients are randomized to 1 of 6 treatment arms (as of 6/1/2005, patients are randomized to treatment arms I and IV only; arms II, III, V, and VI are closed to accrual). As of 8/18/2008, pre-screening for KRAS status was added with mutant KRAS (or KRAS not evaluable) patients put on arm G and wild-type KRAS patients randomized between arm A and arm D. ARM A: Patients receive oxaliplatin intravenously (IV) over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46-48 hours on days 1. Treatment repeats every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease. ARM B (closed to accrual as of 6/1/2005--currently enrolled patients may cross over to arm I for remainder of therapy): Patients receive irinotecan hydrochloride IV over 2 hours on day 1 and leucovorin calcium and fluorouracil as in arm A. Treatment repeats every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease. ARM C (closed to accrual as of 6/1/2005--currently enrolled patients may cross over to arm I for remainder of therapy): Patients receive 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. ARM D: Patients receive cetuximab\* IV over 1 hour on days 1 and 8 and oxaliplatin, leucovorin calcium, and fluorouracil as in arm A. Treatment repeats every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease. ARM E (closed to accrual as of 6/1/2005--currently enrolled patients may cross over to arm D for remainder of therapy): Patients receive cetuximab\* as in arm D and irinotecan hydrochloride, leucovorin calcium, and fluorouracil as in arm B. Treatment repeats every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease. ARM F (closed to accrual as of 6/1/2005--currently enrolled patients may cross over to arm D for remainder of therapy): Patients receive cetuximab\* as in arm D and chemotherapy as in arm C. ARM G (added as of 8/18/2008, mutant KRAS (or KRAS not evaluable) patients): Locally directed therapy. NOTE: \*Cetuximab is administered over 2 hours at a higher dose on day 1 of course 1 only. Quality of life (QOL) is assessed at baseline, 3 months, and at the end of therapy. As of 8/18/2008, QOL was discontinued. Patients are followed for a maximum of 8 years from randomization.

Conditions

• Adenocarcinoma of the Colon
• Stage III Colon Cancer

Interventions

Type	Name	Description
DRUG	irinotecan hydrochloride	Given IV
DRUG	oxaliplatin	Given IV
DRUG	leucovorin calcium	Given IV
DRUG	fluorouracil	Given IV
BIOLOGICAL	cetuximab	Given IV
DRUG	Locally Directed Therapy	Patients determined to have mutated KRAS (or KRAS not evaluable) will be assigned to an event monitoring arm in which adjuvant therapy will be determined and assigned by the treating oncologist. The determination of the type of therapy, duration of treatment, and dose modification will be the responsibility of the treating oncologists.

Timeline

• Start date: 2004-02-01
• Primary completion: 2012-11-01
• Completion: 2012-11-01
• First posted: 2004-03-10
• Last updated: 2020-05-13
• Results posted: 2015-02-09

Locations

894 sites across 3 countries: United States, Canada, Puerto Rico