Valproic Acid in Treating Patients With Kaposi's Sarcoma

AIDS Malignancy Consortium

Status

Completed

Conditions

Sarcoma

Treatments

Drug: valproic acid

Study type

Interventional

Funder types

NETWORK

Industry

NIH

Identifiers

NCT00075777

U01CA070019 (U.S. NIH Grant/Contract)

AMC-038

CDR0000349348 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment

19 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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
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