Colon Cancer
Conditions
Keywords
Colon Cancer
Brief summary
This trial will evaluate the combination of modified infusional 5-fluorouracil/ leucovorin, oxaliplatin (FOLFOX6), bevacizumab, and cetuximab in patients with metastatic colorectal cancer. FOLFOX6 has proven to be a safe and effective regimen in first line treatment of advanced colorectal cancer. The role of epidermal growth factor (EGFR) inhibitors in an earlier treatment setting in combination with optimal chemotherapy regimens is an important emerging question.
Detailed description
All patients received cetuximab: 400 mg/m2 (first cycle only) administered intravenously (IV) on day 1 and 250 mg/m2 IV on day 8 with all subsequent cycles 250 mg/m2 IV on days 1 and 8. Day 1 cetuximab was immediately followed by bevacizumab 5 mg/kg IV, oxaliplatin 85 mg/m2 IV, and 5-fluorouracil 400 mg/m2 IV bolus, followed by 2400 mg/m2 administered as a continuous infusion over 46 hours via a pump (outpatient) and leucovorin 350 mg IV (modified FOLFOX6). Cycles were 14 days.
Interventions
DRUGBevacizumab
5 mg/kg IV
DRUGCetuximab
400 mg/m2 (first cycle only) IV on day 1 and 250 mg/m2 IV on day 8 with all subsequent cycles 250 mg/m2 IV on days 1 and 8
DRUG5-fluorouracil
400 mg/m2 bolus IV bolus followed by 2400 mg/m2 administered as continuous IV infusion over 46 hours via pump (outpatient)
DRUGLeucovorin
350 mg IV
DRUGOxaliplatin
85 mg/m2 IV
Sponsors
Bristol-Myers Squibb
SCRI Development Innovations, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
To be included in the study, you must meet the following criteria: * Metastatic colorectal cancer confirmed by a biopsy sample * 18 years of age or older * Evidence of disease progression at time of study entry * At least one prior adjuvant chemotherapy regimen * No prior therapy for metastatic disease * Measurable disease * Able to perform activities of daily living with minimal assistance * Adequate bone marrow, kidney, and liver function * Tumor tissue available for assessment of EGFR * Signed informed consent
Exclusion criteria
You cannot participate in the study if any of the following apply to you: * Treatment with a previous regimen for metastatic disease * Prior treatment with any EGFR inhibitor or anti-angiogenic agents * Brain or nervous system metastases * History of severe thromboembolic event * Clinical evidence or history of bleeding or coagulopathy * History of stroke or heart attack within six months * Poorly controlled hypertension * Non-healing wound, ulcer, or bone fracture * History of abdominal fistula, perforation, or abscess within six months * Other uncontrolled or significant disease or medical condition Please note: There are additional inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment | 18 months | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease | 18 months | Progression Free Survival (PFS) is defined as the interval between the start date of treatment and the date of occurrence of progressive disease or death. |
| Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death | 36 months | Measured from the date of first treatment until the date of death from any cause |
| Number of Patients With Adverse Events as a Measure of Safety With FOLFOX6 Combined With Bevacizumab and Cetuximab | 18 months | The toxicity assessments were made according to the common terminology criteria for adverse events (CTCAE version 3.0) of the National Cancer Institute. Number of participants with Grade 1 to 5 adverse events are reported here. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bevacizumab/Cetuximab/FOLFOX Bevacizumab 5 mg/kg IV Cetuximab 400 mg/m2 (first cycle only) IV on day 1 and 250 mg/m2 IV on day 8 with all subsequent cycles 250 mg/m2 IV on days 1 and 8 5-Fluorouracil 400 mg/m2 bolus IV bolus followed by 2400 mg/m2 administered as continuous IV infusion over 46 hours via pump (outpatient) Leucovorin 350 mg IV Oxaliplatin 85 mg/m2 IV | 36 |
| Total | 36 |
Baseline characteristics
| Characteristic | Bevacizumab/Cetuximab/FOLFOX |
|---|---|
| Age, Continuous | 55 years |
| Region of Enrollment United States | 36 participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 31 / 31 | 5 / 5 |
| serious Total, serious adverse events | 14 / 31 | 2 / 5 |
Outcome results
Primary
Overall Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: 18 months
Population: This study was originally designed as a randomized study with patients receiving FOLFOX and bevacizumab with or without cetuximab. Following an amendment, all patients received cetuximab, FOLFOX and bevacizumab. The 5 patients randomized prior to the amendment that did not receive cetuximab are excluded from the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab/Cetuximab/FOLFOX | Overall Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment | 55 percentage of patients |
Secondary
Number of Patients With Adverse Events as a Measure of Safety With FOLFOX6 Combined With Bevacizumab and Cetuximab
The toxicity assessments were made according to the common terminology criteria for adverse events (CTCAE version 3.0) of the National Cancer Institute. Number of participants with Grade 1 to 5 adverse events are reported here.
Time frame: 18 months
Population: This study was originally designed as a randomized study with patients receiving FOLFOX and bevacizumab with or without cetuximab. Following an amendment, all patients received cetuximab, FOLFOX and bevacizumab. The 5 patients randomized prior to the amendment that did not receive cetuximab are excluded from the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Bevacizumab/Cetuximab/FOLFOX | Number of Patients With Adverse Events as a Measure of Safety With FOLFOX6 Combined With Bevacizumab and Cetuximab | 31 Participants |
Secondary
Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death
Measured from the date of first treatment until the date of death from any cause
Time frame: 36 months
Population: This study was originally designed as a randomized study with patients receiving FOLFOX and bevacizumab with or without cetuximab. Following an amendment, all patients received cetuximab, FOLFOX and bevacizumab. The 5 patients randomized prior to the amendment that did not receive cetuximab are excluded from the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab/Cetuximab/FOLFOX | Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death | 25.7 months |
Secondary
Progression Free Survival (PFS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease
Progression Free Survival (PFS) is defined as the interval between the start date of treatment and the date of occurrence of progressive disease or death.
Time frame: 18 months
Population: This study was originally designed as a randomized study with patients receiving FOLFOX and bevacizumab with or without cetuximab. Following an amendment, all patients received cetuximab, FOLFOX and bevacizumab. The 5 patients randomized prior to the amendment that did not receive cetuximab are excluded from the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab/Cetuximab/FOLFOX | Progression Free Survival (PFS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease | 9 months |