Colorectal Cancer
Conditions
Keywords
stage IV colon cancer, stage IV rectal cancer, adenocarcinoma of the colon, adenocarcinoma of the rectum
Brief summary
RATIONALE: Drugs used in chemotherapy, such as irinotecan, floxuridine, and leucovorin, 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, 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 may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with bevacizumab works in treating patients with stage IV colorectal cancer.
Detailed description
For the purpose of this study treatment cycle consist of six weeks, 2 weeks of consecutive treatment followed by 1 week of rest and 2 weeks of treatment followed by one week of rest. Treatment will be administered weekly, 4 out 6 weeks, on days 1, 8, 22 and 29 according to the schedule. There will be no treatment delivered on weeks 3 & 6 (Days 15 and 36). Disease will be evaluated by CT scan at the completion of every two cycles. Patients with complete response (CR), or partial response (PR), will be evaluated for possible surgical resection. Patients who become operable will continue to be evaluated for survival and disease relapse. Patients with stable disease (SD), and those with less than pCR after surgery should continue chemotherapy until radiographic evidence of tumor progression is identified or unacceptable side effects.
Interventions
BIOLOGICALBevacizumab
DRUGFloxuridine
DRUGIrinotecan
DRUGLeucovorin
Sponsors
University of Miami
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
1. Patients must have stage IV, histologically confirmed diagnosis of Adenocarcinoma of the colon. 2. Patients must have bi-dimensionally measurable disease since the purpose of this study is to determine efficacy of treatment. 3. Patients must be previously untreated. 4. Patients must be over the age of 18 years. 5. Patients may not be pregnant. Patients of childbearing years must be using contraception. 6. Patients must have ECOG performance status of 0-1 or KPS of at least 70. 7. Patients must have life expectancy of ≥ two months. 8. Patients must have a white blood cell count of ≥1000/mm³ ANC \> 1.0, platelets \> 100,000/mm³. 9. Patients must have adequate renal function as documented by a serum creatinine of ≤ 1.5 mg/dl. 10. Patients must have a bilirubin of ≤ 1.5 mg/dl and an SGOT of ≤ three times normal for patients with no liver disease, and ≤ five times normal for those with liver metastases. 11. Patients must be informed of the investigational nature of the study and give written informed consent. 12. Patients must have indwelling central venous catheter or good peripheral intravenous catheter, preferably a port-a-cath. 13. Patients may have had prior surgery for their colorectal cancer. Patients must be at least 8 weeks beyond surgery and recovered from all effects of surgery. 14. Patients enrolled in this study may have a history of prior malignancy (5 years ago) provided that the patient is currently disease-free.
Exclusion criteria
1. Patients who have had prior chemotherapy or radiation therapy for their colorectal cancer, with exception of adjuvant chemo/radiation therapy. 2. Patients receiving concomitant radiation, hormonal therapy, chemotherapy, or immunotherapy. 3. Patients receiving any investigational drug within 30 days prior to start of this study. 4. Patients with serious underlying medical illnesses (including Congestive Heart Failure New York Heart Association Functional Classification 2-4) or active infection. 5. Patients with central nervous system metastasis must have completed radiation prior to entry into this protocol. 6. Patients with psychiatric conditions or associated conditions which would make participating in this study dangerous to their health. 7. Patients with uncontrolled hypertension.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival up to 2 Years | 2 years | Percentage of patients with overall survival times of up to 2 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate (Complete Response and Partial Response) | 2 years | Percentage of patients achieving complete response or partial response per RECIST criteria ver 1.0 |
| Median Progression-free Survival in Months | 2 years | Median number of months subjects achieved progression-free survival |
| Rate of Toxicity in Study Participants | 2 years | Evaluation the safety and toxicities of protocol regimen as evidenced by the rate of serious adverse events in study participants. |
Countries
United States
Participant flow
Pre-assignment details
A total of 25 subjects were enrolled however; data were analyzed for only 22 of the subjects enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Combination Chemotherapy and Bevacizumab Treatment cycle is 6 weeks, 2 weeks of consecutive treatment followed by 1 week of rest and 2 weeks of treatment followed by one week of rest. Treatment will be administered weekly, 4 out 6 weeks, on days 1, 8, 22 and 29:
* Bevacizumab: 7.5mg/kg via intravenous (IV) infusion on Days 1 and 22;
* Irinotecan: 110 mg/m\^2 via IV infusion on Days 1, 8, 22, 29;
* Leucovorin: 500 mg/m\^2 via IV infusion on Days 1, 8, 22 and 29;
* Floxuridine: 120 mg/kg over continuous infusion on Days 1, 8, 22 and 29. | 22 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 3 |
Baseline characteristics
| Characteristic | Combination Chemotherapy and Bevacizumab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 6 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants |
| Age, Continuous | 57 years |
| Region of Enrollment United States | 22 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 5 / 22 |
| other Total, other adverse events | 0 / 22 |
| serious Total, serious adverse events | 11 / 22 |
Outcome results
Primary
Overall Survival up to 2 Years
Percentage of patients with overall survival times of up to 2 years
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combination Chemotherapy and Bevacizumab | Overall Survival up to 2 Years | 61 percentage of participants |
Secondary
Median Progression-free Survival in Months
Median number of months subjects achieved progression-free survival
Time frame: 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Combination Chemotherapy and Bevacizumab | Median Progression-free Survival in Months | 13 months |
Secondary
Rate of Toxicity in Study Participants
Evaluation the safety and toxicities of protocol regimen as evidenced by the rate of serious adverse events in study participants.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combination Chemotherapy and Bevacizumab | Rate of Toxicity in Study Participants | 50 percentage of participants |
Secondary
Response Rate (Complete Response and Partial Response)
Percentage of patients achieving complete response or partial response per RECIST criteria ver 1.0
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combination Chemotherapy and Bevacizumab | Response Rate (Complete Response and Partial Response) | 67 percentage of participants |