Single-Arm, Dose-Finding Pilot Trial of Single-Agent Bortezomib in Patients With Relapsed/Refractory AIDS-Associated Kaposi Sarcoma With Correlative Assessments of KSHV and HIV

Inclusion Criteria:

- Adult patients with cutaneous AIDS-related biopsy-proven KS relapsed after or
refractory to at least one other prior systemic therapy

- Patients must have cutaneous KS lesion(s) amenable to biopsy (either one lesion >= 12
mm or 3 >= 4 mm) in addition to at least 5 lesions measurable for assessment; all of
these lesions must not have been previously radiated

- Must have been on stable anti-retroviral therapy for at least 12 weeks with a
PI-based or NNRTI-based regimen of at least three drugs, with no intention to change
the regimen for the duration of the study; patients who have a high likelihood of
better HIV management with a new antiretroviral regimen should defer enrollment until
the changes are in place and the new HAART regimen meets the 12 week criteria

- Serologic documentation of HIV infection at any time prior to study entry, as
evidenced by positive ELISA, positive western blot, or other FDA-approved licensed
HIV test, or a detectable blood level of HIV RNA

- Women of child-bearing potential must have a negative pregnancy test within 72 hours
before initiation of study drug dosing; post-menopausal women must be amenorrheic for
at least 12 months to be considered of non-childbearing potential; male and female
subjects of reproductive potential must agree to employ an effective barrier method
of birth control throughout the study and for up to 3 months following
discontinuation of study drug; (Note: A woman of childbearing potential is one who is
biologically capable of becoming pregnant; this includes women who are using
contraceptives or whose sexual partners are either sterile or using contraceptives)

- ANC >= 1,000/mm^3; subjects may be receiving growth factor support to meet these
criteria

- Hemoglobin >= 8.0 gm/dL; subjects may be receiving growth factor support to meet
these criteria

- Platelets >= 100,000/mm^3; subjects may be receiving growth factor support to meet
these criteria

- Total bilirubin =< 1.5 mg/dL; if the elevated bilirubin is felt to be secondary to
indinavir or atazanavir therapy, then subjects will be allowed on protocol without
any limit on the total bilirubin if the direct bilirubin is normal

- AST(SGOT) and ALT(SGPT) =< 2.5 X institutional upper limit of normal (ULN)

- Serum creatinine =< institutional ULN or creatinine clearance >= 50 mL/min/1.73 m^2
for subjects with creatinine levels above institutional ULN

- Pre-existing grade 3 or 4 peripheral neuropathy

Exclusion Criteria:

- KS that is improving in the 4 weeks prior to enrollment

- Symptomatic visceral KS (oral and lymph node involvement is eligible)

- Symptomatic pulmonary KS; asymptomatic pulmonary KS that is not limiting activities
of daily living is allowable

- ECOG performance status greater than 2

- Expected survival < 3 months with standard KS treatments (i.e., radiation,
paclitaxel)

- Concurrent active opportunistic infection (OI)

- Herpes zoster (shingles) outbreak within the last 6 months or inability to take
herpes zoster prophylaxis

- Patient is ≤ 5 years free of another primary malignancy except if the other primary
malignancy is neither currently clinically significant nor requiring active
intervention, or if the other primary malignancy is a localized squamous or basal
cell skin cancer or cervical/anal carcinoma in situ

- Acute treatment for an infection or other serious medical illness within 14 days
prior to study entry

- Patients may not have had anti-neoplastic treatment for Kaposi sarcoma (including
chemotherapy, radiation therapy, biological therapy, or investigational therapy)
within 4 weeks (6 weeks for nitrosourea or mitomycin-C) of study treatment

- Prior treatment with bortezomib or other investigational proteasome inhibitors

- Previous local therapy of any KS indicator lesion within 60 days, unless the lesion
has clearly progressed with enlargement since the local therapy

- Use of any investigational drug or treatment within 4 weeks prior to randomization

- Physical or psychiatric conditions that in the estimation of the investigator place
the patient at high risk of toxicity or non-compliance

- Hypersensitivity to boron

- Subjects with grade III/IV cardiac disease as defined by the New York Heart
Association criteria. (e.g., congestive heart failure, myocardial infarction within 6
months of study)

- Subject has an acute or known chronic liver disease (e.g., chronic active hepatitis,
cirrhosis); subjects with known hepatitis B or C infection may be enrolled if they
have either documentation of no or minimal fibrosis on liver biopsy or undetectable
hepatitis virus on PCR

- Systemic corticosteroid treatment, other than replacement doses

- Female subjects who are pregnant or breast-feeding