Adenocarcinoma of the Colon, Stage III Colon Cancer
Conditions
Brief 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.
Interventions
DRUGirinotecan hydrochloride
Given IV
DRUGoxaliplatin
Given IV
DRUGleucovorin calcium
Given IV
DRUGfluorouracil
Given IV
BIOLOGICALcetuximab
Given IV
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.
Sponsors
National Cancer Institute (NCI)
Eastern Cooperative Oncology Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease-free Survival (Arms A and D: Wild-type KRAS Patients) | At 3 years | The primary endpoint for this study was to compare the disease-free survival (DFS) in patients with stage III colon cancer who are KRAS wild-type randomized to one of two treatment regimens: 1) oxaliplatin, leucovorin calcium, and fluorouracil (Arm A) or 2) oxaliplatin, leucovorin calcium, fluorouracil and cetuximab (Arm D). Participants treated according to Arms B, C, E, and F treatment schedules received treatment which included irinotecan hydrochloride and therefore were not analyzed for this endpoint. Disease-free survival is defined as the time from randomization until tumor recurrence or death, whichever is first. Estimated by the method of Kaplan and Meier. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease-free Survival (Arms A and D: Mutant KRAS Patients) | At 3 years | A secondary endpoint for this study was to investigate the disease-free survival (DFS) in patients with stage III colon cancer who are KRAS mutant (or KRAS-nonevaluable) and randomized to one of two treatment regimens: 1) oxaliplatin, leucovorin calcium, and fluorouracil (Arm A) or 2) oxaliplatin, leucovorin calcium, fluorouracil and cetuximab (Arm D). Participants treated according to Arms B, C, E, and F treatment schedules received treatment which included irinotecan hydrochloride and therefore were not analyzed for this endpoint. Disease-free survival is defined as the time from randomization until tumor recurrence or death, whichever is first. Estimated by the method of Kaplan and Meier. |
| Overall Survival as Measured by the 3-year Event-free Rate (Arms A and D: Wild-type KRAS Patients) | Up to 3 years | Evidence of death from any cause within 3 years counted as events in the time to event- Kaplan Meier analysis of overall survival for patients with stage III colon cancer who are KRAS wild-type randomized to one of two treatment regimens: 1) oxaliplatin, leucovorin calcium, and fluorouracil (Arm A) or 2) oxaliplatin, leucovorin calcium, fluorouracil and cetuximab (Arm D). Participants treated according to Arms B, C, E, and F treatment schedules received treatment which included irinotecan hydrochloride and therefore were not analyzed for this endpoint. The 3-year event free rates (percentage) are reported below for Wild-type KRAS Patients. |
| Overall Survival as Measured by the 3-year Event-free Rate (Arms A and D: Mutant KRAS Patients) | Up to 3 years | Evidence of death from any cause within 3 years counted as events in the time to event- Kaplan Meier analysis of overall survival for patients with stage III colon cancer who are KRAS mutant (or KRAS-nonevaluable) and randomized to one of two treatment regimens: 1) oxaliplatin, leucovorin calcium, and fluorouracil (Arm A) or 2) oxaliplatin, leucovorin calcium, fluorouracil and cetuximab (Arm D). Participants treated according to Arms B, C, E, and F treatment schedules received treatment which included irinotecan hydrochloride and therefore were not analyzed for this endpoint. The 3-year event-free rates (percentage) are report below for mutant KRAS patients. |
| Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (v3) (Arms A and D: Wild-type KRAS Patients) | Assessed up to 8 years | The maximum grade for each type of toxicity will be recorded for each patient with stage III colon cancer who are KRAS wild-type randomized to one of two treatment regimens: 1) oxaliplatin, leucovorin calcium, and fluorouracil (Arm A) or 2) oxaliplatin, leucovorin calcium, fluorouracil and cetuximab (Arm D). The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below. |
| Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (v3) (Arms A and D: Mutant KRAS Patients) | Assessed up to 8 years | The maximum grade for each type of toxicity will be recorded for each patient with stage III colon cancer who are KRAS mutant (or KRAS-nonevaluable) and randomized to one of two treatment regimens: 1) oxaliplatin, leucovorin calcium, and fluorouracil (Arm A) or 2) oxaliplatin, leucovorin calcium, fluorouracil and cetuximab (Arm D). The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below. |
Countries
Canada, Puerto Rico, United States
Contacts
PRINCIPAL_INVESTIGATORSteven A Alberts, MD
North Central Cancer Treatment Group
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 | 1,402 |
| 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 | 111 |
| 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 | 111 |
| 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 | 1,350 |
| 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 | 45 |
| 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 | 46 |
| 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. | 332 |
| Total | 3,397 |
Baseline characteristics
| Characteristic | 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 |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 58 years | 57 years | 60 years | 58 years | 59 years | 60.5 years | 56 years | 58 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 64 Participants | 5 Participants | 3 Participants | 62 Participants | 4 Participants | 2 Participants | 18 Participants | 158 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1107 Participants | 103 Participants | 103 Participants | 1060 Participants | 38 Participants | 41 Participants | 225 Participants | 2677 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 231 Participants | 3 Participants | 5 Participants | 228 Participants | 3 Participants | 3 Participants | 89 Participants | 562 Participants |
| Histologic Grade High | 357 participants | 25 participants | 28 participants | 345 participants | 10 participants | 12 participants | 60 participants | 837 participants |
| Histologic Grade Low | 1045 participants | 86 participants | 83 participants | 1005 participants | 35 participants | 34 participants | 272 participants | 2560 participants |
| KRAS Status Mutant | 391 participants | 33 participants | 43 participants | 345 participants | 15 participants | 13 participants | 326 participants | 1166 participants |
| KRAS Status Unknown | 56 participants | 6 participants | 6 participants | 51 participants | 3 participants | 4 participants | 6 participants | 132 participants |
| KRAS Status Wildtype | 955 participants | 72 participants | 62 participants | 954 participants | 27 participants | 29 participants | 0 participants | 2099 participants |
| Positive Nodes 1-3 | 816 participants | 71 participants | 70 participants | 790 participants | 29 participants | 28 participants | 203 participants | 2007 participants |
| Positive Nodes 4+ | 586 participants | 40 participants | 41 participants | 560 participants | 16 participants | 18 participants | 129 participants | 1390 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 6 Participants | 1 Participants | 1 Participants | 7 Participants | 0 Participants | 0 Participants | 1 Participants | 16 Participants |
| Race (NIH/OMB) Asian | 66 Participants | 4 Participants | 2 Participants | 62 Participants | 3 Participants | 0 Participants | 12 Participants | 149 Participants |
| Race (NIH/OMB) Black or African American | 94 Participants | 6 Participants | 7 Participants | 96 Participants | 5 Participants | 2 Participants | 29 Participants | 239 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 2 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 9 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 8 Participants | 0 Participants | 1 Participants | 7 Participants | 0 Participants | 0 Participants | 0 Participants | 16 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 23 Participants | 0 Participants | 0 Participants | 21 Participants | 0 Participants | 1 Participants | 14 Participants | 59 Participants |
| Race (NIH/OMB) White | 1202 Participants | 98 Participants | 100 Participants | 1154 Participants | 37 Participants | 43 Participants | 275 Participants | 2909 Participants |
| Region of Enrollment Canada | 138 participants | 2 participants | 2 participants | 124 participants | 1 participants | 0 participants | 28 participants | 295 participants |
| Region of Enrollment Jamaica | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Region of Enrollment Puerto Rico | 5 participants | 0 participants | 0 participants | 2 participants | 0 participants | 0 participants | 1 participants | 8 participants |
| Region of Enrollment United States | 1258 participants | 109 participants | 109 participants | 1224 participants | 44 participants | 46 participants | 303 participants | 3093 participants |
| Sex: Female, Male Female | 662 Participants | 53 Participants | 50 Participants | 647 Participants | 20 Participants | 21 Participants | 160 Participants | 1613 Participants |
| Sex: Female, Male Male | 740 Participants | 58 Participants | 61 Participants | 703 Participants | 25 Participants | 25 Participants | 172 Participants | 1784 Participants |
| Tumor Stage Not Availabe | 0 participants | 0 participants | 0 participants | 1 participants | 1 participants | 0 participants | 0 participants | 2 participants |
| Tumor Stage T1 or T2 | 198 participants | 18 participants | 14 participants | 213 participants | 5 participants | 5 participants | 56 participants | 509 participants |
| Tumor Stage T3 | 1046 participants | 78 participants | 93 participants | 983 participants | 35 participants | 39 participants | 214 participants | 2488 participants |
| Tumor Stage T4 | 158 participants | 15 participants | 4 participants | 153 participants | 4 participants | 2 participants | 62 participants | 398 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| other Total, other adverse events | 688 / 1,378 | 53 / 108 | 60 / 108 | 928 / 1,326 | 26 / 42 | 33 / 44 | 0 / 0 |
| serious Total, serious adverse events | 93 / 1,378 | 9 / 108 | 11 / 108 | 150 / 1,326 | 4 / 42 | 5 / 44 | 0 / 0 |
Outcome results
Primary
Disease-free Survival (Arms A and D: Wild-type KRAS Patients)
The primary endpoint for this study was to compare the disease-free survival (DFS) in patients with stage III colon cancer who are KRAS wild-type randomized to one of two treatment regimens: 1) oxaliplatin, leucovorin calcium, and fluorouracil (Arm A) or 2) oxaliplatin, leucovorin calcium, fluorouracil and cetuximab (Arm D). Participants treated according to Arms B, C, E, and F treatment schedules received treatment which included irinotecan hydrochloride and therefore were not analyzed for this endpoint. Disease-free survival is defined as the time from randomization until tumor recurrence or death, whichever is first. Estimated by the method of Kaplan and Meier.
Time frame: At 3 years
Population: The analysis was performed using intention to treat principles. All patients that were wild-type KRAS and received randomized treatment according to the Arm A or Arm D intervention schedule were evaluated for this endpoint. Any patient receiving irinotecan was not included in the evaluation of this endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Wild-type KRAS Arm A | Disease-free Survival (Arms A and D: Wild-type KRAS Patients) | 74.6 percentage of participants |
| Wild-type KRAS Arm D | Disease-free Survival (Arms A and D: Wild-type KRAS Patients) | 71.5 percentage of participants |
Secondary
Disease-free Survival (Arms A and D: Mutant KRAS Patients)
A secondary endpoint for this study was to investigate the disease-free survival (DFS) in patients with stage III colon cancer who are KRAS mutant (or KRAS-nonevaluable) and randomized to one of two treatment regimens: 1) oxaliplatin, leucovorin calcium, and fluorouracil (Arm A) or 2) oxaliplatin, leucovorin calcium, fluorouracil and cetuximab (Arm D). Participants treated according to Arms B, C, E, and F treatment schedules received treatment which included irinotecan hydrochloride and therefore were not analyzed for this endpoint. Disease-free survival is defined as the time from randomization until tumor recurrence or death, whichever is first. Estimated by the method of Kaplan and Meier.
Time frame: At 3 years
Population: The analysis was performed using intention to treat principles. All patients that were KRAS mutant (or not evaluable for KRAS) and received randomized treatment according to the Arm A or Arm D intervention schedule were evaluated for this endpoint. Any patient receiving irinotecan was not included in the evaluation of this endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Wild-type KRAS Arm A | Disease-free Survival (Arms A and D: Mutant KRAS Patients) | 67.1 percentage of participants |
| Wild-type KRAS Arm D | Disease-free Survival (Arms A and D: Mutant KRAS Patients) | 65.0 percentage of participants |
Secondary
Overall Survival as Measured by the 3-year Event-free Rate (Arms A and D: Mutant KRAS Patients)
Evidence of death from any cause within 3 years counted as events in the time to event- Kaplan Meier analysis of overall survival for patients with stage III colon cancer who are KRAS mutant (or KRAS-nonevaluable) and randomized to one of two treatment regimens: 1) oxaliplatin, leucovorin calcium, and fluorouracil (Arm A) or 2) oxaliplatin, leucovorin calcium, fluorouracil and cetuximab (Arm D). Participants treated according to Arms B, C, E, and F treatment schedules received treatment which included irinotecan hydrochloride and therefore were not analyzed for this endpoint. The 3-year event-free rates (percentage) are report below for mutant KRAS patients.
Time frame: Up to 3 years
Population: The analysis was performed using intention to treat principles. All patients that were KRAS mutant (or not evaluable for KRAS) and received randomized treatment according to the Arm A or Arm D intervention schedule were evaluated for this endpoint. Any patient receiving irinotecan was not included in the evaluation of this endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Wild-type KRAS Arm A | Overall Survival as Measured by the 3-year Event-free Rate (Arms A and D: Mutant KRAS Patients) | 87.9 percentage of participants |
| Wild-type KRAS Arm D | Overall Survival as Measured by the 3-year Event-free Rate (Arms A and D: Mutant KRAS Patients) | 82.7 percentage of participants |
p-value: 0.2595% CI: [0.85, 1.92]Regression, Cox
Secondary
Overall Survival as Measured by the 3-year Event-free Rate (Arms A and D: Wild-type KRAS Patients)
Evidence of death from any cause within 3 years counted as events in the time to event- Kaplan Meier analysis of overall survival for patients with stage III colon cancer who are KRAS wild-type randomized to one of two treatment regimens: 1) oxaliplatin, leucovorin calcium, and fluorouracil (Arm A) or 2) oxaliplatin, leucovorin calcium, fluorouracil and cetuximab (Arm D). Participants treated according to Arms B, C, E, and F treatment schedules received treatment which included irinotecan hydrochloride and therefore were not analyzed for this endpoint. The 3-year event free rates (percentage) are reported below for Wild-type KRAS Patients.
Time frame: Up to 3 years
Population: The analysis was performed using intention to treat principles. All patients that were wild-type KRAS and received randomized treatment according to the Arm A or Arm D intervention schedule were evaluated for this endpoint. Any patient receiving irinotecan was not included in the evaluation of this endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Wild-type KRAS Arm A | Overall Survival as Measured by the 3-year Event-free Rate (Arms A and D: Wild-type KRAS Patients) | 87.3 percentage of participants |
| Wild-type KRAS Arm D | Overall Survival as Measured by the 3-year Event-free Rate (Arms A and D: Wild-type KRAS Patients) | 85.6 percentage of participants |
p-value: 0.1595% CI: [0.92, 1.68]Regression, Cox
Secondary
Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (v3) (Arms A and D: Mutant KRAS Patients)
The maximum grade for each type of toxicity will be recorded for each patient with stage III colon cancer who are KRAS mutant (or KRAS-nonevaluable) and randomized to one of two treatment regimens: 1) oxaliplatin, leucovorin calcium, and fluorouracil (Arm A) or 2) oxaliplatin, leucovorin calcium, fluorouracil and cetuximab (Arm D). The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below.
Time frame: Assessed up to 8 years
Population: All patients that were mutant KRAS and received randomized treatment according to the Arm A or Arm D intervention schedule and completed the adverse event form at least once were evaluated for this endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Wild-type KRAS Arm A | Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (v3) (Arms A and D: Mutant KRAS Patients) | 55.6 percentage of patients |
| Wild-type KRAS Arm D | Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (v3) (Arms A and D: Mutant KRAS Patients) | 72.3 percentage of patients |
p-value: <0.001Chi-squared
Secondary
Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (v3) (Arms A and D: Wild-type KRAS Patients)
The maximum grade for each type of toxicity will be recorded for each patient with stage III colon cancer who are KRAS wild-type randomized to one of two treatment regimens: 1) oxaliplatin, leucovorin calcium, and fluorouracil (Arm A) or 2) oxaliplatin, leucovorin calcium, fluorouracil and cetuximab (Arm D). The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below.
Time frame: Assessed up to 8 years
Population: All patients that were wild-type KRAS and received randomized treatment according to the Arm A or Arm D intervention schedule and completed the adverse event form at least once were evaluated for this endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Wild-type KRAS Arm A | Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (v3) (Arms A and D: Wild-type KRAS Patients) | 51.1 percentage of patients |
| Wild-type KRAS Arm D | Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (v3) (Arms A and D: Wild-type KRAS Patients) | 73.3 percentage of patients |
p-value: <0.001Chi-squared