Valproic Acid in Treating Patients With Kaposi's Sarcoma

Sponsor

AIDS Malignancy Consortium (Other)

Overall Status

Completed

CT.gov ID

NCT00075777

Collaborator

National Cancer Institute (NCI) (NIH), The Emmes Company, LLC (Industry)

Enrollment

Locations

Duration (Months)

1.5

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Sarcoma	Drug: valproic acid	N/A

Detailed 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

19 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Feb 1, 2005

Actual Primary Completion Date :

Jul 1, 2007

Actual Study Completion Date :

Feb 1, 2008

Outcome Measures

Primary Outcome Measures

Toxicity-related discontinuation rate [28 days]
Lytic induction rate [28 days]
Clinical response rate [28 days]
Accelerated KS progression rate [28 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Jonsson Comprehensive Cancer Center at UCLA	Los Angeles	California	United States	90095-1781
2	Veterans Affairs Medical Center - San Diego	San Diego	California	United States	92161
3	UCSF Comprehensive Cancer Center	San Francisco	California	United States	94143-0324
4	Georgia Cancer Center for Excellence at Grady Memorial Hospital	Atlanta	Georgia	United States	30303
5	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois	United States	60611-3013
6	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410
7	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
8	Siteman Cancer Center at Barnes-Jewish Hospital	Saint Louis	Missouri	United States	63110
9	Albert Einstein Cancer Center at Albert Einstein College of Medicine	Bronx	New York	United States	10461
10	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
11	Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44106-5065
12	Joan Karnell Cancer Center at Pennsylvania Hospital	Philadelphia	Pennsylvania	United States	19106
13	Floyd & Delores Jones Cancer Institute at Virginia Mason Medical Center	Seattle	Washington	United States	98111

Sponsors and Collaborators

AIDS Malignancy Consortium
National Cancer Institute (NCI)
The Emmes Company, LLC

Investigators

Study Chair: Richard F. Ambinder, MD, PhD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study Chair: Mary Jo Lechowicz, MD, Georgia Cancer Center for Excellence at Grady Memorial Hospital