A Phase I/II Trial of PTC299 in Patients With HIV-Related Kaposi's Sarcoma

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Biopsy-proven Kaposi sarcoma (KS) involving the skin (with or without lymph node),
oral cavity, gastrointestinal (GI) tract, and/or lung

- Patients with GI and/or pulmonary involvement must be asymptomatic or minimally
symptomatic and not require systemic cytotoxic chemotherapy

- Has at least five bidimensionally measurable cutaneous lesions that have not been
previously irradiated AND can be used as indicator lesions

- Must have a sufficient number of non-indicator cutaneous lesions measuring ≥ 4 x
4 mm available to obtain a total of four 3-mm punch biopsies (two at baseline
and two during the course of study treatment)

- Serologic documentation of HIV infection, as evidenced by positive ELISA, western
blot, or other federally approved licensed HIV test OR a detectable blood level of
HIV RNA

- Patients receiving antiretroviral therapy for HIV infection are eligible provided
they have been on a stable regimen for ≥ 12 weeks prior to study entry AND there is
no evidence of improvement in KS during those 12 weeks or there is evidence of
progression of KS within the immediate 4 weeks prior to study entry

- No symptomatic visceral KS requiring cytotoxic therapy

PATIENT CHARACTERISTICS:

- Karnofsky performance status 60-100%

- Life expectancy ≥ 3 months

- Absolute neutrophil count ≥ 1,000/mm³

- Platelet count ≥ 75,000/mm³

- Hemoglobin ≥ 8 g/dL

- Creatinine ≤ 2.0 mg/dL

- Total bilirubin normal (grade 0)

- No specific limit of total serum bilirubin for patient receiveing indinavir or
atazanavir therapy AND direct serum bilirubin ≤ 30% of total bilirubin

- AST and ALT ≤ 2.5 times upper limit of normal (grade 1)

- INR and aPTT normal

- Proteinuria < 2+

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective barrier contraception during and for up to 3
months after completion of study treatment

- Capable of complying with the study, in the opinion of the investigator

- No acute, active opportunistic infection (other than oral thrush or genital herpes)
within the past 14 days

- No other concurrent neoplasia requiring cytotoxic therapy

- No history of any of the following:

- Myocardial infarction

- Severe/unstable angina

- Coronary/peripheral artery bypass graft

- Symptomatic congestive heart failure

- Cerebrovascular accident

- Transient ischemic attack

- Pulmonary embolism

- Deep vein thrombosis

- Other significant thromboembolic event

- No known coagulopathy or bleeding diathesis

- No history of CNS, pulmonary, GI, or urinary bleeding

- No known history of drug-induced liver injury

- Resting systolic blood pressure ≤ 160 mm Hg or diastolic blood pressure ≤ 100 mm Hg

- No history of or ongoing clinically significant illness, medical condition, surgical
history, physical finding, ECG finding, or laboratory abnormality that, in the
opinion of the investigator, could affect the safety of the patient, alter the
absorption of the study drug, or impair the assessment of study results

PRIOR CONCURRENT THERAPY:

- More than 4 weeks since prior and no other concurrent anti-neoplastic therapy for KS,
including chemotherapy, radiotherapy, local therapy, or biological therapy

- More than 60 days since prior local therapy for any KS-indicator lesion unless the
lesion has clearly progressed since treatment

- Any prior local therapy for indicator lesions (regardless of the elapsed time)
should not be allowed unless there is evidence of clear-cut progression of that
lesion

- More than 28 days since prior and no other concurrent investigational drugs or
therapy (other than antiretroviral therapy or agents available on a treatment IND)

- More than 30 days since prior major surgery and recovered

- More than 14 days since prior treatment for an acute infection (other than oral
thrush or genital herpes) or other serious medical illness

- No concurrent surgical procedures

- No concurrent systemic corticosteroid therapy, other than replacement doses

- No concurrent anticoagulant therapy, including warfarin, heparin (including low
molecular weight heparin), or antiplatelet drugs (e.g., clopidogrel bisulfate)

- Concurrent aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) allowed
provided the dose does not exceed the maximum recommended dose