RATIONALE: Valproic acid may help stop the growth of Kaposi's sarcoma cells by blocking the enzymes necessary for tumor cell growth.

PURPOSE: Clinical trial to determine the effectiveness of valproic acid in treating patients who have HIV-related Kaposi’s sarcoma.

Condition	Treatment or Intervention
recurrent Kaposi's sarcoma epidemic Kaposi's sarcoma	Drug: valproic acid  Procedure: biological response modifier therapy  Procedure: enzyme inhibitor therapy  Procedure: non-specific immune-modulator therapy

Further Study Details: 

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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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

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

Georgia
      Georgia Cancer Center for Excellence at Grady Memorial Hospital, Atlanta,  Georgia,  30303,  United States; Recruiting
Maryland
      Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,  Maryland,  21231,  United States; Recruiting

Study chairs or principal investigators

Richard Frederick Ambinder, MD, PhD,  Sidney Kimmel Cancer Center   
Mary Jo Lechowicz, MD,  Study Chair,  Georgia Cancer Center for Excellence at Grady Memorial Hospital   

Study ID Numbers:  CDR0000349348; AMC-038; NCT00075777
Record last reviewed:  February 2005
Last Updated:  February 8, 2005
Record first received:  January 9, 2004
ClinicalTrials.gov Identifier:  NCT00075777
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08