A Phase II Trial of COL-3 in Patients With HIV Related Kaposi's Sarcoma

PRIMARY OBJECTIVES:

I. To evaluate the tumor response rate and response duration of treatment with Col-3 at two
different dose levels- 50 mg/day and 100 mg/day in subjects with HIV related KS.

II. To evaluate the biologic activity of Col-3 by measuring percent apoptotic cells on tumor
biopsies pre- and post-treatment.

III. To evaluate the effect of Col-3 on serum levels of MMP-2 and MMP-9.

SECONDARY OBJECTIVES:

I. To determine the safety and toxicity of Col-3 at two different dose levels in HIV related
KS.

II. To evaluate the effect of Col-3 on overall quality of life. III. To evaluate the
relationship between clinical response and quantitative measures of KSHV/HHV-8 and HIV viral
load.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are randomized to 1 of
2 treatment arms.

Arm I: Patients receive low-dose oral COL-3 once daily.

Arm II: Patients receive high-dose oral COL-3 once daily.

Treatment on both arms continues in the absence of disease progression or unacceptable
toxicity. Quality of life is assessed.

Patients are followed for at least 1 month.

PROJECTED ACCRUAL: A total of 70 patients (35 per treatment arm) will be accrued for this
study within 1.75 years.

Inclusion Criteria:

- Biopsy proven KS involving the skin , lymph nodes, oral cavity, gastrointestinal (GI)
tract and/or lungs; GI and pulmonary involvement must be asymptomatic or minimally
symptomatic and not require systemic cytotoxic therapy; at least five measurable,
previously non-radiated, cutaneous lesions must be present which can be used as
indicator lesions

- Serologic documentation of HIV infection at any time prior to study entry, as
evidenced by positive ELISA, positive Western Blot, or other federally approved
licensed HIV test

- Karnofsky performance status >= 60%

- Hemoglobin >= 8.0 gm/dl

- Absolute neutrophil count >= 750 cells/mm^3

- Platelet count >= 75,000/mm^3

- Serum creatinine =< 1.5 mg/dl or a measured creatinine clearance of > 60 ml/min

- Total bilirubin should be normal; if, however, the elevated bilirubin is felt to be
secondary to indinavir therapy, then subjects will be allowed on protocol if bilirubin
< 3.5 mg/dl, provided that the direct bilirubin is normal

- AST (SGOT) and ALT (SGPT) =< 2.5 times the ULN

- PT and PTT < 120% of normal

- Life expectancy of 3 months or more

- Ability and willingness to give informed consent

- All women of childbearing potential must have a negative serum beta HCG within 72
hours prior to study entry and must practice adequate birth control to prevent
pregnancy while receiving study treatment and for 3 months after treatment is
discontinued; all males of child fathering potential must also practice adequate birth
control; pregnant or breast feeding females are excluded from participation in this
study since the effects of Col-3 on an unborn or young child are unknown and may
potentially be toxic

- Subjects must, in the opinion of the investigator, be capable of complying with this
protocol

Exclusion Criteria:

- Concurrent active opportunistic infection (OI)

- Concurrent neoplasia requiring cytotoxic therapy

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

- Prior anti-neoplastic treatment for KS within 3 weeks of study entry; patients must
also have completely recovered from any associated toxicity

- Previous local therapy of any KS indicator lesion within 60 days, unless the lesion
has progressed since treatment; because of the possibility of tattooing and the
difficulty in ascertaining clinically what is active KS versus residual pigment post
treatment, any prior local treatment to the indicator lesions regardless of the
elapsed time should not be allowed unless there is evidence of clear-cut progression
of said lesion

- Anti-retroviral therapy is permitted but not required; if patients are taking
anti-retroviral therapy, their regimen must not have changed within 4 weeks of
starting the study medication; patient should be receiving an optimal and stable
regimen of HAART for a minimum of 4 weeks prior to entry

- Subjects must not have received blood products within 4 weeks of study entry and must
not have received granulocyte colony stimulating factor or erythropoietin within 2
weeks of study entry

- Evidence of a prior MI or cardiac ischemia