Pilot Study of Liposomal Doxorubicin Combined With Bevacizumab Followed by Bevacizumab Monotherapy in Adults With Advanced Kaposi's Sarcoma

Inclusion Criteria

-INCLUSION CRITERIA:

1. Age greater than or equal to 18 years

2. Kaposi's sarcoma pathologically confirmed by CCR pathology

3. Evaluable KS involving the skin and/or viscera, including at least one of the
following:

- KS of the skin with greater than or equal to 5 KS lesions that are evaluable by
non-invasive methods that have not been treated with local therapeutic
modalities

- Pulmonary KS evaluable by CT scan

- Gastrointestinal KS evaluable by direct visualization or fiberoptic
instrumentation

- Biopsy proven lymph node involvement measurable by CT scan

4. ECOG performance status less than or equal to 2

5. Life expectancy > 6 months

6. At least one of the following indications for therapy:

- Pulmonary involvement

- Visceral involvement

- Pain

- Edema

- Substantial lymph node involvement

- Ulcerating lesions

- Decreased range of joint motion due to KS

- Multiple lesions not amenable to local therapy

- Significant psychological impact leading to social withdrawal

7. Patients with HIV infection must be willing to comply with a regimen of highly active
antiretroviral therapy (HAART).

8. Patients may have received any number of prior therapies, including monotherapy with
liposomal doxorubicin or bevacizumab

9. Blood pressure

-SBP < 150 mm/Hg

-DBP < 90 mm/Hg

- Patients receiving anti-hypertensive medicines must be on a stable regimen for at
least 1 month

10. EF > 50% by MUGA

11. The following hematologic parameters:

-Hemoglobin > 9 g/dl

-WBC > 1000/mm(3)

-ANC > 750/mm(3)

-Platelets > 75,000/mm(3)

-PT and PTT less than or equal to 120% of control, unless patient has the presence of
a lupus anticoagulant

12. The following hepatic parameters:

-Bilirubin less than or equal to 1.5 times ULN unless the patient is receiving
protease inhibitor therapy (i.e. indinavir, ritonavir, nelfinavir, and atazanavir)
known to be associated with increased bilirubin: in this case total bilirubin less
than or equal to 7.5 mg/dl and the direct fraction is less than or equal to 0.7
mg/dl.

-AST/GOT less than or equal to 2.5 times the upper limit of normal

13. Either serum creatinine less than or equal to 1.5 mg/dL or measured creatinine
clearance greater than or equal to 60 mL/min

14. Either urine protein < 1+ or measured 24 hour urine protein < 500 milligram

15. Able to take aspirin 81mg daily.

16. Study participant must use birth control measure prior to study entry (during
screening), during study participation, and for 12 weeks after bevacizumab is
discontinued.

17. Inclusion of women and minorities: Both men and women and members of all races and
ethnic groups are eligible for this trial.

EXCLUSION CRITERIA:

1. Inability to provide informed consent.

2. KS therapy other than HAART within 3 weeks.

3. History of cumulative doxorubicin or liposomal doxorubicin dose > 430 mg/m(2).

4. Supraphysiologic doses of corticosteroids within 3 weeks.

5. Major surgical procedure (including periodontal) within 4 weeks.

6. Surgical or other non-healing wounds, other than KS ulcers.

7. Pregnancy (because of unknown potential for fetal malformation).

.8. Breast feeding (because of unknown potential for adverse infant developmental
consequences).

9. Has an uncontrolled illness including, but not limited to, ongoing or active infection
requiring IV antibiotics, symptomatic congestive heart failure, unstable angina pectoris,
cardiac arrhythmia, cirrhosis, or psychiatric illness/social situations that would limit
adherence to study requirements.

10. Past or present history of malignant tumors other than KS unless: a) in a complete
remission for greater than or equal to 1 year from the time a response was first
documented; b) completely resected basal cell carcinoma; or c) in situ squamous cell
carcinoma of the cervix or anus

11. Severe or life-threatening infection within 2 weeks of entry onto the study.

12. History of deep venous or arterial thrombotic disease (including but not limited to,
acute myocardial infarction due to coronary thrombosis, ischemic stroke, and peripheral
arterial disease), unless:

- Line-related thrombosis withouth embolus

- Occurring greater than or equal to 1 year prior to screening

13. Known procoagulant disorder including prothrombin gene mutation 20210,
antithrombin III deficiency, protein c deficiency, protein S deficiency and
antiphospholipid syndrome but not including heterozygosity for the Factor V Leiden
mutation or the presence of a lupus anticoagulant in the absence of other criteria
for the antiphospholipid syndrome.

14. Known bleeding diathesis.

15. History of severe gastrointestinal bleeding within 6 months. Patients with
gastrointestinal blood loss due to KS may be included.

16. Hemoptysis within 4 weeks.

17. Substantial CNS disease including.

- History of CNS bleeding.

- Mass lesions in the brain.

- Uncontrolled seizure disorder.

- Recent history of CVA (e.g. within the past 6 months).

18. Proteinuria > 500 mg/24hrs.

19. Patients with any other abnormality that would be scored as a grade 3 or greater
toxicity, except:

- Lymphopenia

- Direct manifestations of KS

- Direct manifestation of HIV

- Direct manifestation of HIV therapy (i.e. Hyperbilirubinemia associated with protease
inhibitors)

- Asymptomatic hyperuricemia

- Hypophosphatemia

20. Previous bevacizumab within 6 weeks prior to enrollment.

21. Known hypersensitivity to bevacizumab, Chinese hamster ovary cell products, or
other recombinant human or humanized antibodies.

22. Any other condition, including the presence of laboratory abnormalities, which in
the opinion of the Principal Investigator or Lead Associate Investigator, places the
subject at unacceptable risk if ther were to participate in the study or confounds
the ability to interpret data from the study.