Phase II Study of Doxorubicin and Avastin® in Sarcoma.
Condition: Sarcoma; Soft Tissue Sarcoma
MeSH terms: Sarcoma
Intervention: Avastin; Doxorubicin
Intervention description: Combination of Avastin and doxorubicin. If initial 90 +/- 15 minute infusion of Avastin is tolerated without fever and chills, the 2nd dose may be infused over 60 +/- 10 minutes. If well tolerated, all subsequent infusions may be delivered over 30 +/- 10 minutes.; The Day 1 6- hour continuous IV infusion must be done through a central venous catheter.
Intervention MeSH terms: Bevacizumab; Doxorubicin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: STS

Summary:

      This research is being done to find out if adding a drug called Avastin to an already
      approved regimen used for soft-tissue sarcoma, Doxorubicin, will improve overall survival,
      and slow disease progression. The study will also evaluate the overall safety of combining
      these drugs. It is not known if combining these drugs will improve outcome. Avastin has been
      approved for the treatment of metastatic carcinoma of the colon or rectum. It is not approved
      for the treatment of soft-tissue sarcoma when added to Doxorubicin.
    

Eligibility criteria:

        Inclusion Criteria:

          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
             age

          8. No prior use of mesna, adriamycin, ifosfamide or Avastin®.

          9. Baseline ECHO or MUGA with LVEF > or = 50-60%.

         10. Age ≥ 18

        Exclusion Criteria:

          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®
             cancer study

          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
             Appendix E)

          7. History of myocardial infarction or unstable angina within 6 months prior to study
             enrollment

          8. History of stroke or transient ischemic attack within 6 months prior to study
             enrollment

          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