• Antitumor effect by Kaposi's sarcoma (KS) response criteria in patients with HIV-associated KS [ Designated as safety issue: No ]
  

• Antitumor effect by Kaposi's sarcoma (KS) response criteria in patients with classic KS [ Designated as safety issue: No ]
  
• Toxicity profile by NCI CTC version 2.0 in patients with HIV-associated KS or classic KS [ Designated as safety issue: Yes ]
  
• Progression-free survival [ Designated as safety issue: No ]
  
• Response as measured by changes in SDF-1 expression [ Designated as safety issue: No ]
  
• Changes in HHV-8 viral load in peripheral blood mononuclear cells [ Designated as safety issue: No ]
  
• Changes in serum vascular endothelial growth factor (VEGF) levels [ Designated as safety issue: No ]
  
• Changes in viral interleukin-6 levels [ Designated as safety issue: No ]
  

OBJECTIVES:

• Determine, preliminarily, the antitumor effect of bevacizumab in patients with classic or epidemic (AIDS-associated) Kaposi's sarcoma.
• Determine the toxicity of this drug in these patients.
• Determine, preliminarily, the progression-free survival of patients treated with this drug.

OUTLINE: Patients receive a loading dose of bevacizumab IV over 90 minutes. Beginning 1 week later, patients receive bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed at 3 to 6 weeks.

PROJECTED ACCRUAL: A total of 8-27 patients will be accrued for this study within 1 year.

DISEASE CHARACTERISTICS:

• Histologically confirmed Kaposi's sarcoma (KS) by Center for Cancer Research (CCR)
• At least 5 assessable cutaneous lesions previously untreated by local therapy
• No symptomatic, extensive pulmonary involvement
• No symptomatic visceral KS, excluding the oral cavity

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• More than 6 months

Hematopoietic

• WBC > 1,000/mm^3
• Absolute neutrophil count > 750/mm^3
• Platelet count > 75,000/mm^3
• Hemoglobin > 9 g/dL
• No coagulopathy

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN) except for patients receiving protease inhibitor therapy known to be associated with increased bilirubin (e.g., indinavir, ritonavir, nelfinavir, or atazanavir); in this case, total bilirubin ≤ 7.5 mg/dL and the direct fraction ≤ 0.7 mg/dL
• AST/ALT ≤ 2.5 times ULN
• PT and PTT ≤ 120% of control (unless due to the presence of a lupus anticoagulant)
• INR ≤ 1.5 OR
• INR 2-3 for patients receiving stable-dose warfarin or low molecular weight heparin AND no active bleeding or pathological conditions that carry a high risk of bleeding (tumor-involving major vessels)

Renal

• Creatinine ≤ 1.5 mg/dL OR
• Creatinine clearance ≥ 60 mL/min
• Urine protein < 1+ OR
• 24-hour urine protein < 500 mg

Cardiovascular

• No history of deep vein or arterial thrombosis
• No clinically significant cardiovascular disease
• No clinically significant peripheral artery disease
• No cardiovascular accident within the past 6 months
• No transient ischemic attack within the past 6 months
• No uncontrolled hypertension (systolic blood pressure must be < 160 mm Hg and diastolic blood pressure < 95 mm Hg)
• No unstable angina
• No myocardial infarction
• No New York Heart Association grade II or greater congestive heart failure
• No cardiac arrhythmia requiring medication
• No grade II or greater peripheral vascular disease

Pulmonary

• See Disease Characteristics

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

• No substantial CNS disease, including the following:

  • History of CNS bleeding
  • Mass lesions of the brain
  • Uncontrolled seizure disorder
• No other prior or concurrent malignant tumors except completely resected basal cell skin cancer, in situ squamous cell carcinoma of the cervix or anus, or any other cancer in complete remission for at least 1 year
• No history of gastrointestinal bleeding
• No evidence of a severe or life-threatening infection within the past 2 weeks
• No concurrent condition requiring IV antibiotics
• No surgical or other nonhealing wound unrelated to KS
• No unstable bone fractures that are not stress/weight bearing able

• No other abnormality that would be scored as a grade 3 toxicity except for the following:

  • Lymphopenia
  • Direct manifestations of KS
  • Direct manifestations of HIV
  • Direct manifestations of HIV therapy (i.e., hyperbilirubinemia associated with protease inhibitors)
  • Asymptomatic hyperuricemia
• No known hypersensitivity to bevacizumab
• No known hypersensitivity to Chinese hamster ovary cell products
• No known hypersensitivity to other recombinant human or humanized antibodies
• No other condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• HIV-positive patients must be willing to comply with a regimen of highly active antiretroviral therapy (HAART) and meet 1 of the following criteria:

  • Be on a regimen of HAART selected for best potential efficacy for at least 1 month with evidence of KS progression on the regimen
  • Be on an optimized regimen of HAART for at least 4 months with no evidence of KS progression
• More than 30 days since prior IV immunoglobulin or monoclonal antibody therapy
• No prior bevacizumab
• No concurrent immunomodulatory agents
• No concurrent cytokines except epoetin alfa or filgrastim (G-CSF)

Chemotherapy

• More than 3 weeks since prior chemotherapy
• No concurrent cytotoxic chemotherapy for KS

Endocrine therapy

• More than 3 weeks since prior supraphysiologic doses of corticosteroids
• No concurrent systemic glucocorticoid steroids

Radiotherapy

• No concurrent radiotherapy for KS

Surgery

• More than 4 weeks since prior major surgery (including periodontal)

Other

• See Hepatic
• No prior SU5416 (semaxanib)
• No other concurrent anticoagulation therapy
• No concurrent chronic daily aspirin (325 mg or more per day) or nonsteroidal anti-inflammatory medication interfering with platelet function
• No concurrent IV antibiotics on day of study drug infusion
• No concurrent topical anti-KS medications
• No other concurrent therapies for KS