A Multi-Institutional, Open-Label, Phase II Study Of Doxorubicin And Bevacizumab (Anti-VEFG Monoclonal Antibody, NSC 704865) For Patients With Advanced Or Metastatic Soft-Tissue Sarcoma

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed soft tissue sarcoma

- Locally recurrent or metastatic disease

- At least 1 unidimensionally measurable lesion

- At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan

- No prior or concurrent known brain metastases

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- Karnofsky 80-100% OR

- ECOG 0-1

Life expectancy

- Not specified

Hematopoietic

- Absolute neutrophil count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

- No bleeding diathesis or coagulopathy

Hepatic

- Bilirubin no greater than 1.2 mg/dL

- AST and ALT no greater than 2.5 times upper limit of normal

- PT and aPTT normal

Renal

- Creatinine no greater than 1.5 mg/dL OR

- Creatinine clearance at least 60 mL/min

- No proteinuria (must be less than 500 mg protein per 24 hours)

Cardiovascular

- Cardiac ejection fraction at least 50% by echocardiogram or MUGA

- No history of deep vein thrombosis

- No clinically significant cardiovascular disease

- No uncontrolled hypertension

- No myocardial infarction

- No unstable angina

- No New York Heart Association grade II-IV congestive heart failure

- No serious cardiac arrhythmia requiring medication

- No grade II or greater peripheral vascular disease within the past year

Pulmonary

- No history of pulmonary embolism

Other

- No symptomatic peripheral neuropathy grade 2 or greater

- No other neoplastic disease within the past 5 years except curatively treated basal
cell skin cancer or carcinoma in situ of the cervix

- No prior allergic reactions attributed to compounds of similar chemical or biological
composition to bevacizumab (including products derived from Chinese hamster ovary
cells), doxorubicin, or dexrazoxane

- No HIV-positive patients receiving combination antiretroviral therapy

- No ongoing or active infection

- No psychiatric illness or social situations that would preclude study entry

- No other uncontrolled concurrent illness

- No serious, non-healing wound ulcer or bone fracture

- No significant traumatic injury within the past 3 weeks

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

- See Chemotherapy

- At least 4 weeks since prior immunotherapy and recovered

- No other concurrent immunotherapy

Chemotherapy

- No prior doxorubicin or any other anthracyclines

- No more than 1 prior chemotherapy regimen

- The following are not considered prior chemotherapy:

- Immunotherapy, including cytokines

- Peroxisome-proliferator-activated receptor gamma agonists or thalidomide

- At least 4 weeks since prior chemotherapy (6 weeks for carmustine or mitomycin) and
recovered

- No other concurrent chemotherapy

Endocrine therapy

- Not specified

Radiotherapy

- At least 4 weeks since prior radiotherapy and recovered

- No concurrent radiotherapy

Surgery

- At least 3 weeks since prior major surgical procedure or open biopsy

- At least 1 week since prior needle biopsy

Other

- No other concurrent investigational agents

- No concurrent full-dose anticoagulants (except to maintain patency of preexisting,
permanent indwelling IV catheters) or thrombolytic agent

- Concurrent warfarin allowed if INR less than 1.5

- No concurrent chronic daily aspirin (more than 325 mg/day) or nonsteroidal anti
-inflammatory medications known to inhibit platelet function

- No other concurrent investigational or commercial agents or therapies for this
malignancy