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

Study Overview
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Brief Summary
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RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for their growth. PURPOSE: This phase II trial is studying how well imatinib mesylate works in treating patients with HIV-related Kaposi's sarcoma.

Detailed Description
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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.

Official Title
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A Phase II Trial Of Imatinib Mesylate (Gleevec) In Patients With HIV Related Kaposi's Sarcoma

Conditions
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Sarcoma

Intervention / Treatment
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* Drug: imatinib mesylate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Imatinib mesylate<br>Imatinib mesylate (Gleevec) taken 400 mg orally once a day for up to 6 months | Drug: imatinib mesylate<br>* 400 mg orally once a day for up to 6 months.<br>* Other names: Gleevec;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients Who Achieve a Clinical Response | Clinical response = Complete Response (absence of residual disease) or Partial Response defined as no new lesions (skin or oral), or no new visceral sites of involvement (or the appearance or worsening of tumor-associated edema or effusions); AND 50% or greater decrease in the number of lesions lasting for >4 weeks; OR Complete flattening of at least 50% of all previously raised lesions OR A 50% decrease in the sum of the products of the largest perpendicular diameters of the marker lesions | 20-24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inhibition of Platelet-derived Growth Factor-receptor as Assessed by Immunohistochemistry |  | 12 months | 
| Cytokine Profiles Before and After Imatinib Therapy |  | 12 months | 
| Pharmacokinetic Profile of Imatinib and Antiretrovirals |  | 12 months | 
| Mechanisms of Primary and Secondary Resistance to Imatinib Therapy | Mutations in the juxtamembrane or kinase membrane of the c-kit or PDGF receptors at baseline or time of progression | 12 months | 
| Viral Transcription Profile of Kaposi's Sarcoma-associated Herpesvirus |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AIDS-related Kaposi sarcoma, recurrent Kaposi sarcoma