Valproic Acid in Treating Patients With Kaposi's Sarcoma

This study has been completed.
Sponsor:
Collaborators:
The EMMES Corporation
Information provided by (Responsible Party):
AIDS Malignancy Clinical Trials Consortium
ClinicalTrials.gov Identifier:
NCT00075777
First received: January 9, 2004
Last updated: August 27, 2014
Last verified: August 2014
  Purpose

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 Intervention
Sarcoma
Drug: valproic acid

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Trial Of Valproic Acid In Patients With Kaposi's Sarcoma

Resource links provided by NLM:


Further study details as provided by AIDS Malignancy Clinical Trials Consortium:

Primary Outcome Measures:
  • Toxicity-related discontinuation rate [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  • Lytic induction rate [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  • Clinical response rate [ Time Frame: 28 days ] [ Designated as safety issue: No ]
  • Accelerated KS progression rate [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

Enrollment: 19
Study Start Date: February 2005
Study Completion Date: February 2008
Primary Completion Date: July 2007 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: valproic acid
    250 mg by mouth twice a day
    Other Name: Depakene
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00075777

Locations
United States, California
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, United States, 90095-1781
Veterans Affairs Medical Center - San Diego
San Diego, California, United States, 92161
UCSF Comprehensive Cancer Center
San Francisco, California, United States, 94143-0324
United States, Georgia
Georgia Cancer Center for Excellence at Grady Memorial Hospital
Atlanta, Georgia, United States, 30303
United States, Illinois
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, United States, 60611-3013
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, Missouri
Siteman Cancer Center at Barnes-Jewish Hospital
Saint Louis, Missouri, United States, 63110
United States, New York
Albert Einstein Cancer Center at Albert Einstein College of Medicine
Bronx, New York, United States, 10461
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
United States, Ohio
Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106-5065
United States, Pennsylvania
Joan Karnell Cancer Center at Pennsylvania Hospital
Philadelphia, Pennsylvania, United States, 19106
United States, Washington
Floyd & Delores Jones Cancer Institute at Virginia Mason Medical Center
Seattle, Washington, United States, 98111
Sponsors and Collaborators
AIDS Malignancy Clinical Trials Consortium
The EMMES Corporation
Investigators
Study Chair: Richard F. Ambinder, MD, PhD Sidney Kimmel Comprehensive Cancer Center
Study Chair: Mary Jo Lechowicz, MD Georgia Cancer Center for Excellence at Grady Memorial Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: AIDS Malignancy Clinical Trials Consortium
ClinicalTrials.gov Identifier: NCT00075777     History of Changes
Other Study ID Numbers: AMC-038, U01CA070019, CDR0000349348
Study First Received: January 9, 2004
Last Updated: August 27, 2014
Health Authority: United States: Federal Government

Keywords provided by AIDS Malignancy Clinical Trials Consortium:
recurrent Kaposi sarcoma
AIDS-related Kaposi sarcoma

Additional relevant MeSH terms:
Sarcoma, Kaposi
Sarcoma
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Vascular Tissue
Valproic Acid
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
GABA Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs

ClinicalTrials.gov processed this record on August 28, 2014