Clinical trial NCT00449163: Combination Chemotherapy and Bevacizumab in Treating Patients With Stage IV Colorectal Cancer
Official title: Phase II Study of Avastin, Irinotecan, High Dose 24 Hour Continuous Intravenous Infusion of Floxuridine and Leucovorin in Patients With Previously Untreated Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: stage IV colon cancer
stage IV rectal cancer
adenocarcinoma of the colon
adenocarcinoma of the rectum
Lead sponsor: University of Miami
Sponsor class: OTHER
First posted: 2007-03-19
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Overall Survival up to 2 Years
timeFrame: 2 years
Secondary outcomes:
measure: Response Rate (Complete Response and Partial Response)
timeFrame: 2 years
measure: Median Progression-free Survival in Months
timeFrame: 2 years
measure: Rate of Toxicity in Study Participants
timeFrame: 2 years
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami
state: Florida
Study officials:
affiliation: University of Miami
name: Bach Ardalan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Phase II study of bevacizumab (B), camptosar (I), high-dose 24-hour continuous intravenous infusion of floxuridine (F) and leucovorin (L) in patients with previously untreated metastatic colon cancer. (B-IFL) B. Ardalan, M. Feagans, D. Mezentsev, C. Jones, P. R. Subbarayan, G. Walker, M. Sapp, K. Stephenson, J. Ness, D. Franceschi, and A. Livingstone Journal of Clinical Oncology 2009 27:15S, e15114-e15114