Phase II Study of Doxorubicin and Avastin® for Patients With Advanced Soft-tissue Sarcomas.
1. Pathologically confirmed intermediate or high grade locally advanced or metastatic
soft tissue sarcoma.
2. The presence of measurable disease
3. Normal renal function (spot dipstick <2** or urine protein: creatinine ratio >1.0
4. Normal Hepatic function (total bilirubin within JOHC normal limits, transaminases
(AST and ALT <3 times upper limit of normal
5. Hematologic parameters as defined as ANC >1500/mm³ and Platelets > 100,000/mm³.
6. Performance status 0-1 on ECOG scale
7. Use of effective means of contraception (men and women) in subjects of child-bearing
8. No prior use of mesna, adriamycin, ifosfamide or Avastin®.
9. Baseline ECHO or MUGA with LVEF > or = 50-60%.
10. Age ≥ 18
1. Major surgery within 28 days
2. History of proteinuria > 1+
3. Current, recent (within 4 weeks of the first infusion of this study), or planned
participation in an experimental drug study other than a Genentech-sponsored Avastin®
4. Inadequately controlled hypertension (defined as systolic blood pressure >150 and/or
diastolic blood pressure > 100 mmHg on antihypertensive medications)
5. Any prior history of hypertensive crisis or hypertensive encephalopathy
6. New York Heart Association (NYHA) Grade II or greater congestive heart failure (see
7. History of myocardial infarction or unstable angina within 6 months prior to study
8. History of stroke or transient ischemic attack within 6 months prior to study
9. Symptomatic peripheral vascular disease
10. Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
11. Evidence of bleeding diathesis or coagulopathy
12. Current or recent (within 10 days of enrollment) use of aspirin (>325 mg/day) or
chronic use of other NSAIDs
13. Current, ongoing treatment with full-dose warfarin or its equivalent (i.e.,
unfractionated and/or low molecular weight heparin).
14. Known central nervous system or brain metastases
15. 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
16. Core biopsy or other minor surgical procedure, excluding placement of a vascular
access device, within 7 days prior to study enrollment
17. Pregnant (positive pregnancy test) or lactating
18. Proteinuria :creatinine (UPC) ratio ≥ 1.0 at screening or Urine dipstick for
proteinuria ≥ 2+ (patients discovered to have ≥2+ proteinuria on dipstick urinalysis
at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1g of
protein in 24 hours to be eligible).
19. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 6 months prior to Day 0
20. Serious, non-healing wound, ulcer, or bone fracture
21. Known hypersensitivity to any component of Avastin®
22. Inability to comply with study and/or follow-up procedures