Imatinib Mesylate in Treating Patients With HIV-Related Kaposi's Sarcoma

OBJECTIVES:

Primary

- Determine clinical response in patients with HIV-related Kaposi's sarcoma treated with
imatinib mesylate.

Secondary

- Determine the inhibition of platelet-derived growth factor receptors, as determined by
immunohistochemistry, in patients treated with this drug.

- Determine cytokine profiles before and after treatment with this drug in these patients.

- Determine the pharmacokinetic profile of this drug and antiretrovirals in these
patients.

- Determine mechanisms of primary and secondary resistance to this drug in these patients.

OUTLINE: This is an open-label, multicenter study.

Patients receive oral imatinib mesylate once daily. Treatment continues for up to 1 year in
the absence of disease progression or unacceptable toxicity.

Patients are followed at 30 days.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study within 1 year.

DISEASE CHARACTERISTICS:

- Histologically confirmed Kaposi's sarcoma (KS) involving at least 1 of the following
areas:

- Skin

- Lymph nodes

- Oral cavity

- Gastrointestinal tract*

- Lungs* NOTE: *Must be asymptomatic or minimally symptomatic AND does not require
systemic cytotoxic therapy

- Serological documentation of HIV infection, as evidenced by positive enzyme-linked
immunosorbent assay (ELISA), Western Blot test, or other federally approved licensed
HIV test

- At least 5 measurable, non-irradiated, cutaneous indicator lesions

- Patients must have 3 lesions at least 5 x 5 mm that are accessible for 4 mm punch
biopsy

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- Karnofsky 60-100%

Life expectancy

- At least 3 months

Hematopoietic

- Hemoglobin ≥ 8.0 g/dL

- Absolute neutrophil count ≥ 1,000/mm^3

- Platelet count ≥ 75,000/mm^3

Hepatic

- AST and ALT ≤ 2.5 times upper limit of normal

- Bilirubin normal

- Patients with elevated bilirubin secondary to indinavir or atazanavir allowed
provided total bilirubin is < 3.5 mg/dL AND direct bilirubin is normal

- No acute or known chronic liver disease (e.g., chronic active hepatitis or cirrhosis)

- Hepatitis C infection with minimal or no fibrosis on liver biopsy allowed

Renal

- Creatinine ≤ 1.5 mg/dL OR

- Creatinine clearance > 60 mL/min

Cardiovascular

- No New York Heart Association class III or IV cardiac disease

- No congestive heart failure

- No myocardial infarction within the past 6 months

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective barrier contraception during and for 3 months
after study participation

- No concurrent active opportunistic infection

- No other severe and/or life-threatening medical disease

- No other malignancy within the past 5 years except clinically insignificant malignancy
not requiring active intervention, basal cell skin cancer, or carcinoma in situ of the
cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

- More than 4 weeks since prior biologic therapy for KS

- More than 2 weeks since prior granulocyte colony-stimulating factor

- No concurrent biologic agents for KS

Chemotherapy

- More than 4 weeks since prior chemotherapy for KS (6 weeks for nitrosoureas or
mitomycin)

- No concurrent chemotherapy for KS, including systemic cytotoxic chemotherapy

Endocrine therapy

- No concurrent systemic corticosteroid therapy except replacement doses

Radiotherapy

- See Disease Characteristics

- More than 4 weeks since prior radiotherapy for KS

- No concurrent radiotherapy for KS

Surgery

- More than 2 weeks since prior major surgery

Other

- No prior imatinib mesylate

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

- More than 4 weeks since prior investigational therapy for KS

- More than 4 weeks since other prior therapy for KS

- More than 14 days since prior acute treatment for an infection or other serious
medical illness

- No concurrent warfarin

- No concurrent grapefruit juice

- No other concurrent therapy for KS

- No other concurrent investigational drugs

- Concurrent antiretroviral therapy required except for patients who have exhausted all
available treatment options