| Exclusion Criteria: | 1) Patients with bilateral hydronephrosis which cannot be alleviated by ureteral stents or percutaneous drainage.
2) Patients previously treated with chemotherapy except when used concurrently with radiation therapy. Patients who have received concurrent paclitaxel and/or concurrent topotecan with radiation therapy are ineligible.
3) Patients with craniospinal metastases.
4) Patients with a concomitant malignancy other than non-melanoma skin cancer.
5) Patients with a prior invasive malignancy (except non-melanoma skin cancer) who have had any evidence of disease within the last 5 years or whose prior malignancy treatment contraindicates the current protocol therapy.
6) Patients with serious non-healing wound, ulcer, or bone fracture. This includes history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess for which an interval of 3 to 6 months must pass before study entry. In addition, the patient must have undergone correction (or spontaneous healing) of the perforation/fistula and/or the underlying process causing the fistula/perforation. Patients with granulating incisions healing by secondary intention with no evidence of fascial dehiscence or infection are eligible but require weekly wound examinations.
7) Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels.
8) Patients with history or evidence upon physical examination of CNS disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of treatment on this study.
9) Clinically significant cardiovascular disease includes: 1) Uncontrolled hypertension, defined as systolic > 150 mm Hg or diastolic > 90 mm Hg. 2) Myocardial infarction or unstable angina < 6 mo. prior to regis. 3) New York Heart Association (NYHA) Grade II or greater congestive heart failure. 4) Serious cardiac arrhythmia req. medication. Does not include asymptomatic, atrial fibrillation w/ controlled ventricular rate. 5) CTCAE Grade 2 > peripheral vascular disease (at least brief (<24 hrs) episodes of ischemia managed non-surgically & w/out permanent deficit). 6) History of CVA within 6 mos.
10) Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies.
11) Patients with or anticipating invasive procedures: 1) Major surg.procedure, open biopsy or significant traumatic injury w/in 28 D prior to 1st date of bevacizumab TX. 2) Major surg.procedure anticipated during course of study. Includes, not limited to abdominal surg. (laparotomy or laparoscopy) prior to disease progression, (colostomy or enterostomy reversal, interval or secondary cytoreductive surgery, or 2nd look surgery). Consult Study Chair prior to pt. entry for questions related to classification of surg.procedures. 3) Core biopsy, w/in 7 D prior to randomization.
12) Pregnant or nursing patients. Bevacizumab specifically inhibits VEGF, which is responsible for formation of new blood vessels during development & antibodies can cross the placenta. Bevacizimab should not be administered to pregnant or nursing women. Subjects will be apprised of large potential risk to a developing fetus. Patients of childbearing potential must agree to use contraceptive measures during study therapy & for at least 6 mos. after completion of bevacizumab therapy.
13) Patients who have received prior therapy with any anti-VEGF drug, including bevacizumab.
14) Patients with clinical symptoms or signs of gastrointestinal obstruction and who require parenteral hydration and/or nutrition.
15) Patients with medical history or conditions not otherwise previously specified which in the opinion of the investigator should exclude participation in this study. The investigator should feel free to consult the Study Chair or Study Co-Chairs for uncertainty in this regard.
16) Patients with significant peripheral vascular disease.
17) Patients with pre-existing Grade 2 or greater peripheral neuropathy. |