Valproic Acid in Treating Patients With Kaposi's Sarcoma

Sarcoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00075777
• Other study ID #: AMC-038
• Secondary ID: U01CA070019CDR00
• Status: Completed
• Phase: N/A
• First received: January 9, 2004
• Last updated: August 27, 2014
• Start date: February 2005
• Est. completion date: February 2008

Study information

• Verified date: August 2014
• Source: AIDS Malignancy Consortium
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: February 2008
• Est. primary completion date: July 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Sarcoma
• Sarcoma, Kaposi

Intervention

Drug:
• valproic acid
250 mg by mouth twice a day

Locations

Country	Name	City	State
United States	Georgia Cancer Center for Excellence at Grady Memorial Hospital	Atlanta	Georgia
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Albert Einstein Cancer Center at Albert Einstein College of Medicine	Bronx	New York
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	Case Comprehensive Cancer Center	Cleveland	Ohio
United States	Jonsson Comprehensive Cancer Center at UCLA	Los Angeles	California
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Joan Karnell Cancer Center at Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	Siteman Cancer Center at Barnes-Jewish Hospital	Saint Louis	Missouri
United States	Veterans Affairs Medical Center - San Diego	San Diego	California
United States	UCSF Comprehensive Cancer Center	San Francisco	California
United States	Floyd & Delores Jones Cancer Institute at Virginia Mason Medical Center	Seattle	Washington

Sponsors (3)

Lead Sponsor	Collaborator
AIDS Malignancy Consortium	National Cancer Institute (NCI), The EMMES Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Toxicity-related discontinuation rate		28 days	Yes
Primary	Lytic induction rate		28 days	Yes
Primary	Clinical response rate		28 days	No
Primary	Accelerated KS progression rate		28 days	Yes