Valproic Acid in Treating Patients With Kaposi's Sarcoma

Study Overview
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Brief Summary
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RATIONALE: Valproic acid may help stop the growth of Kaposi's sarcoma cells by blocking the enzymes necessary for tumor cell growth. PURPOSE: This clinical trial is studying valproic acid in treating patients with HIV-related Kaposi's sarcoma.

Detailed Description
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OBJECTIVES: Primary Determine the safety of valproic acid in patients with Kaposi's sarcoma. Determine the effects of this drug on human herpes virus 8 (KSHV) gene expression using polymerase chain reaction and immunohistochemistry in these patients. Secondary Determine the effects of this drug on HIV, KSHV, and Epstein-Barr virus viral loads in the plasma and peripheral blood mononuclear cells of these patients. Determine clinical response in patients treated with this drug. OUTLINE: This is an open-label, pilot, multicenter study. Patients receive oral valproic acid twice daily on days 1-28 followed by a drug taper over 2 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed monthly for 6 months. PROJECTED ACCRUAL: A total of 15-30 patients will be accrued for this study within 1 year.

Official Title
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A Pilot Trial Of Valproic Acid In Patients With Kaposi's Sarcoma

Conditions
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Sarcoma

Intervention / Treatment
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* Drug: valproic acid


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed HIV-related Kaposi's sarcoma (KS) Disease involving the skin and/or lymph nodes No symptomatic visceral disease No oral KS as the only site of disease Slowly progressive or stable disease allowed Slow progression defined as fewer than 5 new lesions per month Must have documented HIV infection by positive ELISA, western Blot, or viral load determination CD4 T-cell count > 50/mm^3 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 ≥ 750/mm^3 Platelet count ≥ 75,000/mm^3 Hepatic Bilirubin ≤ 1.5 times upper limit of normal (ULN)* AST and ALT ≤ 3 times ULN Albumin > 2.5 g/dL NOTE: *Elevated total bilirubin (≤ 3.5 mg/dL) secondary to indinavir therapy allowed provided the direct bilirubin is normal Renal Creatinine < 1.5 times ULN Cardiovascular No prior myocardial infarction No evidence of cardiac ischemia Other Not pregnant Negative pregnancy test Fertile patients must use effective contraception during and for 3 months after study participation No prior lactic acidosis > 2.0 mmoles/L No prior lipoatrophy or hypercholesterolemia secondary to retroviral treatment No concurrent, acute, active opportunistic infection other than oral thrush or genital herpes within the past 14 days No other concurrent neoplasm requiring cytotoxic therapy PRIOR CONCURRENT THERAPY: Biologic therapy More than 2 weeks since prior biologic therapy for KS Chemotherapy More than 2 weeks since prior chemotherapy for KS No concurrent systemic cytotoxic chemotherapy Endocrine therapy Not specified Radiotherapy More than 2 weeks since prior radiotherapy for KS Surgery Not specified Other More than 2 weeks since other prior antineoplastic or local therapy for KS More than 2 weeks since prior investigational therapy for KS More than 60 days since prior local therapy to a KS-marker lesion unless lesion has clearly progressed since therapy More than 1 year since prior valproic acid Concurrent antiretroviral therapy allowed provided regimen has been stable for at least 4 weeks No concurrent zidovudine No other concurrent KS-specific therapy No other concurrent investigational drugs, other than IND-approved antiretroviral agents

Ages Eligible for Study
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Minimum Age: 18 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

| Intervention/Treatment |
| --- |
|Drug: valproic acid|250 mg by mouth twice a day|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity-related discontinuation rate |  | 28 days | 
| Lytic induction rate |  | 28 days | 
| Clinical response rate |  | 28 days | 
| Accelerated KS progression rate |  | 28 days | 

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