Adenocarcinoma of the Rectum, Mucinous Adenocarcinoma of the Colon, Recurrent Colon Cancer, Recurrent Rectal Cancer, Signet Ring Adenocarcinoma of the Colon, Stage IV Colon Cancer, Stage IV Rectal Cancer
Conditions
Brief summary
Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab and cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of colorectal cancer by blocking blood flow to the tumor. Giving combination chemotherapy together with bevacizumab and cetuximab may kill more tumor cells. This phase II trial is studying how well giving combination chemotherapy together with bevacizumab and cetuximab works in treating patients with stage IV colorectal cancer that cannot be removed by surgery.
Detailed description
PRIMARY OBJECTIVES: I. To determine the safety, feasibility of administration, response rates and progression free survival among chemotherapy naïve patients with advanced colorectal cancer treated with FOLFOX6 plus bevacizumab and cetuximab (FBC). II. To determine the survival of patients with advanced colorectal cancer treated with FBC. III. To determine the safety of the current regimen in selected patients who have had prior MoAb therapy. OUTLINE: This is a multicenter study. Patients receive cetuximab IV over 60-120 minutes on day 1 in weeks 1-8. Patients also receive bevacizumab IV over 30-90 minutes, oxaliplatin IV over 2 hours, and leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV continuously over 48 hours on days 1 and 2 of weeks 1, 3, 5, and 7. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. Patients are followed for survival. PROJECTED ACCRUAL: A total of 40-67 patients will be accrued for this study.
Interventions
DRUGfluorouracil
Given IV
BIOLOGICALbevacizumab
Given IV
DRUGoxaliplatin
Given IV
DRUGleucovorin calcium
Given IV
BIOLOGICALcetuximab
Given IV
Sponsors
National Cancer Institute (NCI)
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
* Histologically or cytologically confirmed adenocarcinoma of the colon or rectum which is beyond the scope of surgical resection (MEDRA code:Colorectal neoplasms malignant,Colorectal cancer stage IV,10010035) * Measurable disease, * Life expectancy of greater than 3 months * ECOG performance status =\< 1 * Leukocytes \>= 3,500/uL * Absolute neutrophil count \>= 1,500/uL * Platelets \>= 150,000/uL * Total bilirubin within normal institutional limits * AST(SGOT)/ALT(SGPT) =\< 2.5 X institutional upper limit of normal * Creatinine within normal institutional limits * Patients may not have received prior therapy with bevacizumab or cetuximab * Ability to understand and the willingness to sign a written informed consent document
Exclusion criteria
* Patients who have had radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to radiotherapy administered more than 4 weeks earlier * Patients may not be receiving any other investigational agents * Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events * History of allergic reactions attributed to compounds of similar chemical or biologic composition to any of the agents used in the study * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * Pregnant or lactating women * Serious or non-healing wound, ulcer or bone fracture * Invasive procedures defined as follows: * Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day 1 therapy * Anticipation of need for major surgical procedures during the course of the study * Core biopsy within 7 days prior to D1 therapy * If a patient is on full-dose anticoagulants, the following criteria should be met for enrollment: * The subject must have an in-range INR (usually between 2 and 3) on a stable dose of warfarin or on stable dose of LMW heparin * The subject must not have active bleeding or pathological conditions that carry high risk of bleeding (e.g. tumor involving major vessels, known varices) * Active infection requiring parental antibiotics on D1 * Proteinuria at baseline; subjects unexpectedly discovered to have \>= 1+ proteinuria will undergo a 24-hour urine collection, which will be \< 1000 mg protein/ 24 hours to be allowed participation in the study * No currently active second malignancy other than non-melanoma skin cancer or carcinoma in-situ of the cervix; patients are not considered to have a currently active malignancy if they have completed therapy and have no evidence of recurrence for at least 5 years * Patients with clinically significant cardiovascular disease: * Uncontrolled hypertension * Myocardial infarction or unstable angina \< 6 months prior to registration * New York heart association grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, unstable angina pectoris * Grade II or greater peripheral vascular disease * CVA within 6 months of study entry
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Severe Adverse Event (SAE) Rate | The duration of the study | The primary objective is to evaluate safety in all treated patients specifically the rate of serious adverse events which were defined as grade 5 events, grade 4 hemorrhage or thrombosis or bowel perforation |
| Progression Free Survival Rate | From randomization to the first documented disease progression | — |
Countries
United States
Participant flow
Recruitment details
A total of 67 patients were enrolled from between December 2004 and November 2006
Pre-assignment details
One patient was enrolled but never started treatment
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Combination Chemotherapy) Patients receive cetuximab IV over 60-120 minutes on day 1 in weeks 1-8. Patients also receive bevacizumab IV over 30-90 minutes, oxaliplatin IV over 2 hours, and leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV continuously over 48 hours on days 1 and 2 of weeks 1, 3, 5, and 7. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.
cetuximab: Given IV
bevacizumab: Given IV
oxaliplatin: Given IV
leucovorin calcium: Given IV
fluorouracil: Given IV | 66 |
| Total | 66 |
Baseline characteristics
| Characteristic | Treatment (Combination Chemotherapy) |
|---|---|
| Age, Continuous | 57 years |
| Race/Ethnicity, Customized Asian | 2 participants |
| Race/Ethnicity, Customized Black | 10 participants |
| Race/Ethnicity, Customized Hispanic | 3 participants |
| Race/Ethnicity, Customized White | 51 participants |
| Sex: Female, Male Female | 31 Participants |
| Sex: Female, Male Male | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 63 / 66 |
| serious Total, serious adverse events | 54 / 66 |
Outcome results
Primary
Progression Free Survival Rate
Time frame: From randomization to the first documented disease progression
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Combination Chemotherapy) | Progression Free Survival Rate | 9.6 months |
Primary
Severe Adverse Event (SAE) Rate
The primary objective is to evaluate safety in all treated patients specifically the rate of serious adverse events which were defined as grade 5 events, grade 4 hemorrhage or thrombosis or bowel perforation
Time frame: The duration of the study
Population: 66 patients treated with cetuximab
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (Combination Chemotherapy) | Severe Adverse Event (SAE) Rate | Grade 5 Death | 2 participants |
| Treatment (Combination Chemotherapy) | Severe Adverse Event (SAE) Rate | Grade 4 venous thrombosis | 2 participants |