Completed

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

0 criteria met from your profileSee at a glance how your profile meets each eligibility criteria.
What is being tested

irinotecan hydrochloride

+ leucovorin calcium

+ fluorouracil

DrugBiological
Who is being recruted

Colonic Diseases+8

+ Colonic Neoplasms

+ Digestive System Diseases

From 18 to 99 Years
See all eligibility criteria
How is the trial designed

Treatment Study

Phase 3
Interventional
Study Start: February 2004
See protocol details

Summary

Principal SponsorNational Cancer Institute (NCI)
Last updated: January 14, 2026
Sourced from a government-validated database.Claim as a partner

Study start date: February 1, 2004

Actual date on which the first participant was enrolled.

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.

Official TitleA 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 
NCT00170092NCT00079274
Principal SponsorNational Cancer Institute (NCI)
Last updated: January 14, 2026
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.
Design Details

3397 patients to be enrolled

Total number of participants that the clinical trial aims to recruit.

Treatment Study

These studies test new ways to treat a disease, condition, or health issue. The goal is to see if a new drug, therapy, or approach works better or has fewer side effects than existing options.



Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria

Any sex

Biological sex of participants that are eligible to enroll.

From 18 to 99 Years

Range of ages for which participants are eligible to join.

Healthy volunteers not allowed

If individuals who are healthy and do not have the condition being studied can participate.

Conditions

Pathology

Colonic DiseasesColonic NeoplasmsDigestive System DiseasesDigestive System NeoplasmsGastrointestinal DiseasesGastrointestinal NeoplasmsIntestinal DiseasesIntestinal NeoplasmsNeoplasmsNeoplasms by SiteColorectal Neoplasms

Criteria

Inclusion Criteria: * Histologically confirmed adenocarcinoma of the colon * Stage III disease * No resected stage IV disease * No rectal cancer * Gross inferior (caudad) margin of the primary tumor must be ≥ 12 cm from the anal verge by rigid proctoscopy * Stage III tumor must have been completely resected within the past 56 days * Must have documented en bloc resection in patients with tumor adherence to adjacent structures * Tumor-related obstructions and colonic perforation are allowed * Tumor samples must be available * At least 1 pathologically confirmed positive lymph node * No evidence of residual involved lymph node disease * Synchronous primary colon cancer allowed * No distant metastatic disease * Performance status - Eastern Cooperative Oncology Group (ECOG) 0-2 * Absolute neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Hemoglobin ≥ 9 g/dL * Bilirubin ≤ 1.5 times upper limit of normal (ULN) * Creatinine ≤ 1.5 times ULN * No uncontrolled high blood pressure * No unstable angina * No symptomatic congestive heart failure * No myocardial infarction with the past 6 months * No New York Heart Association class III or IV heart disease * No symptomatic pulmonary fibrosis * No symptomatic interstitial pneumonitis * No prior allergic reaction (known sensitivity) to chimerized or murine monoclonal antibody therapy * No known allergy to platinum compounds * No documented presence of human anti-mouse antibodies (HAMA) * No active uncontrolled bacterial, viral, or systemic fungal infection * HIV negative * No clinically defined AIDS * Not pregnant or nursing * Negative pregnancy test * No men or women of childbearing potential who are unwilling to employ adequate contraception * No inadequately treated gastrointestinal bleeding * No ≥ grade 2 pre-existing peripheral sensory or motor neuropathy * No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or lobular carcinoma in situ in 1 breast * No other concurrent medical condition that would preclude study participation * No concurrent biologic therapy * No prior chemotherapy for colon cancer * No other concurrent chemotherapy * No prior radiotherapy for colon cancer * No concurrent targeted agents * No prior agents directed against epidermal growth factor-receptor * No other concurrent anticancer therapy

Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.
Treatment Groups
Study Objectives

7 intervention groups are designated in this study

This study does not include a placebo group 

Treatment Groups

Group I

Experimental
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.

Group II

Experimental
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.

Group III

Experimental
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.

Group IV

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

Group 5

Experimental
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.

Group 6

Experimental
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.

Group 7

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.

Study Objectives

Primary Objectives

Secondary Objectives

Study Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.

This study has 894 locations

Suspended

Northeast Alabama Regional Medical Center

Anniston, United StatesSee the location
Suspended

Clearview Cancer Institute

Huntsville, United States
Suspended

Mobile Infirmary Medical Center

Mobile, United States
Suspended

Providence Hospital

Mobile, United States
Completed894 Study Centers