| Exclusion Criteria: | 1) Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental therapeutic drug study other than this protocol.
2) Prior full field radiotherapy less than/equal to 4 weeks or limited field radiotherapy less than/equal to 2 weeks prior to treatment.
3) History or presence of central nervous system metastases.
4) Female patients who are pregnant or lactating or men and women of reproductive potential not willing to employ an effective method of birth control during treatment and for 3 months after discontinuing study treatment.
5) A history of prior treatment with bevacizumab or other agents targeting VEGF.
6) Known dihydropyrimidine dehydrogenase deficiency.
7) Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to bevacizumab, irinotecan, 5-FU, or leucovorin.
8) Serious non-healing wound, ulcer, or active bone fracture.
9) Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day 0; anticipation of need for major surgical procedure during the course of the study.
10) Fine needle aspirations or core biopsies within 7days prior to Day 0.
11) For patients who agree to Optional DCE-MRI studies: Cardiac pacemaker, neurostimulator, metal implants other than those specifically approved as safe for use in MR scanners at the magnetic field strength used for these studies, claustrophobia, obesity (weight exceeding equipment limits).
12) Current or recent use of full-dose warfarin (except as required to maintain patency of preexisting, permanent indwelling IV catheters) for subjects receiving warfarin, INR should be < 1.5). Patients may have prophylactic use of low molecular weight heparin, however therapeutic use of heparin or low molecular weight heparin is not acceptable.
13) Evidence of bleeding diathesis or coagulopathy.
14) Patients with a history of another primary malignancy less than/equal to 5 years, with the exception of non-melanoma skin cancer, and carcinoma in situ of uterine cervix.
15) History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0, unless affected area has been removed surgically.
16) Any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study: Uncontrolled high blood pressure, history of labile hypertension, or history of poor compliance with an antihypertensive regimen; Unstable angina; New York Heart Association (NYHA) greater than/equal to grade 2 congestive heart failure
17) Myocardial infarction within 6 months of study enrollment; History of stroke within 6 months of study enrollment; Unstable symptomatic arrhythmia requiring medication (Patients with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal supraventricular tachycardia are eligible); Clinically significant peripheral vascular disease; Uncontrolled diabetes; Serious active or uncontrolled infection
18) History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications.
19) Inability to comply with study and/or follow-up procedures. |