NCT00079274
Comparison of Combination Chemotherapy Regimens With or Without Cetuximab in Treating Patients Who Have Undergone Surgery For Stage III Colon Cancer
PHASE3
COMPLETED
NCT00079274
INTERVENTIONAL
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
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.
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
Adenocarcinoma of the Colon
Stage III Colon Cancer
- TREATMENT
-
- Type: DRUG
- Name: irinotecan hydrochloride
- Description: Given IV
- Arm Group Labels: Arm B (combination chemotherapy), Arm C (combination chemotherapy), Arm E (combination chemotherapy, monoclonal antibody), Arm F (combination chemotherapy, monoclonal antibody)
-
- Type: DRUG
- Name: oxaliplatin
- Description: Given IV
- Arm Group Labels: Arm A (combination chemotherapy), Arm C (combination chemotherapy), Arm D (combination chemotherapy, monoclonal antibody), Arm F (combination chemotherapy, monoclonal antibody)
-
- Type: DRUG
- Name: leucovorin calcium
- Description: Given IV
- Arm Group Labels: 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)
-
- Type: DRUG
- Name: fluorouracil
- Description: Given IV
- Arm Group Labels: 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)
-
- Type: BIOLOGICAL
- Name: cetuximab
- Description: Given IV
- Arm Group Labels: Arm D (combination chemotherapy, monoclonal antibody), Arm E (combination chemotherapy, monoclonal antibody), Arm F (combination chemotherapy, monoclonal antibody)
-
- Type: DRUG
- Name: Locally Directed Therapy
- Description: 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.
- Arm Group Labels: Arm G (Locally directed therapy)
- National Cancer Institute (NCI)